Clinical and Laboratory Data Up on Hospital Admission are Predictors of New-Onset Atrial Fibrillation in Patients Hospitalized Due to COVID-19 Pneumonia

Andrea, Bruno Rustum; Benchimol-Barbosa, Paulo Roberto; Farah, Simone; Monteiro, Alexandra

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Arquivos Brasileiros de Cardiologia

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Original Article • Arq. Bras. Cardiol. 121 (1) • 2024 • https://doi.org/10.36660/abc.20220784 copy

Clinical and Laboratory Data Up on Hospital Admission are Predictors of New-Onset Atrial Fibrillation in Patients Hospitalized Due to COVID-19 Pneumonia

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Background

New-onset atrial fibrillation (NOAF) occurs in patients hospitalized due to COVID-19. It is still unknown whether clinical and laboratory data assessed upon hospital admission have predictive value for NOAF.

Objectives

To analyze, upon hospital admission, variables with predictive potential for the occurrence of NOAF in patients with COVID-19 pneumonia.

Methods

Observational, retrospective, case-control study. Electronic medical reports of consecutive patients, 60 years of age or older, hospitalized due to COVID-19 pneumonia between March 1st and July 15^th, 2020, were reviewed. Non-paired Student or chi-squared tests compared variables. A Cox proportional hazard model was employed to identify independent predictors of NOAF. P value < 0.05 was considered statistically significant.

Results

Among 667 patients hospitalized due to COVID-19, 201 (30.1%) fulfilled the inclusion criteria. NOAF was documented in 29 patients (14.4%), composing group 1. Group 2 was composed of 162 patients without NOAF. Ten patients were excluded due to the AF rhythm upon hospital admission. In groups 1 and 2, there were differences in overall in-hospital survival rate (24.1 % vs. 67.9%; p<0.001), length of stay in ICU (11.1 ± 10.5 days vs. 4.9 ± 7.5 days; p=0.004) and need for mechanical ventilation rate (82.9% vs. 32.7%; p<0.001). In the Cox model, age > 71 y/o (HR=6.8; p<0.001), total leukocyte count ≤ 7,720 cels.μL-¹ (HR=6.6; p<0.001), serum [Na+] ≤ 137 mEq.L-¹ (HR=5.0; p=0.001), SAPS3 score > 55 (HR=5.6; p=0.002), and disorientation (HR=2.5; p=0.04) on admission were independent predictors of NOAF.

Conclusion

NOAF is a common arrhythmia in elderly hospitalized patients with COVID-19 pneumonia. Clinical and laboratory parameters evaluated on admission have a predictive value for the occurrence of NOAF during hospitalization.

Keywords:
COVID-19; Atrial Fibrillation; Prognosis; Hospitalization; Predictive Value of Tests

COVID-19 Pneumonia Hospitalization Timeline. The arrow indicates the direction of events after the onset of symptoms (left to right). Below are the most relevant events after the onset of symptoms, with their respective visual representations. On the arrow, the time intervals between the demarcated events are presented as mean±SD. After the start of symptoms, hospital admission occurred, on average, in 7.3 ± 3.1 days. They are highlighted in the box corresponding to the Hospital Admission event the five characteristics (independent predictors and respective optimal cut-off values) associated with the development of New-Onset Atrial Fibrillation (NOAF), throughout hospitalization. Note subsequent events, orotracheal intubation (OTI) and invasive mechanical ventilation (MV), which precede the occurrence of NOAF. On average, NOAF occurred 3.5 ± 4.8 days after OTI+MV. OTI: orotracheal intubation; MV: invasive mechanical ventilation; NOAF: new atrial fibrillation; SAPS3: Simplified Acute Physiology Score III.

Variables	NOAF (n=29)	Non-NOAF (n=162)	p value	RR for NOAF
Age (years)^* * mean ± SD.	73.9 ± 8.5	69.8 ± 7.4	0.008^† † Other comorbidities included alcoholism, ex-smoking, Alzheimer's disease, rheumatoid arthritis and vasculitis, cerebrovascular disease, dementia, depression, dyslipidemia, gout, hypothyroidism, osteoporosis, peripheral arterial disease, aortic aneurysm, history of deep vein thrombosis.
Female (n (%))	8 (27.6)	69 (42.6)	0.189^‡ ‡ Comparison using chi-square test.	0.56 CI 95% [0.26 – 1.19]
Systemic arterial hypertension (n (%))	24 (82.8)	118 (72.8)	0.326^‡ ‡ Comparison using chi-square test.	1.56 CI 95% [0.63 – 3.86]
Diabetes mellitus (n (%))	11 (37.9)	73 (45.1)	0.574^‡ ‡ Comparison using chi-square test.	0.75 CI 95% [0.38 – 1.50]
Coronary artery disease (n (%))	8 (28.6)	28 (17.6)	0.248^‡ ‡ Comparison using chi-square test.	1.55 CI 95% [0.74 – 3.23]
Chronic renal disease (n (%))	5 (17.2)	24 (14.8)	0.738^‡ ‡ Comparison using chi-square test.	1.09 CI 95% [0.45 – 2.62]
Chronic obstructive pulmonary disease (n (%))	4 (13.8)	15 (9.3)	0.647^‡ ‡ Comparison using chi-square test.	1.38 CI 95% [0.54 – 3.53]
Asthma (n (%))	0 (0.0)	2 (1.2)	0.924^‡ ‡ Comparison using chi-square test.	N/A
Obesity (n (%))	8 (30.8)	35 (26.7)	0.755^‡ ‡ Comparison using chi-square test.	1.13 CI 95% [0.53 – 2.40]
BMI (kg/m²)*	28.1 ± 14.2	28.4 ± 14.7	0.674^§ § Comparison using unpaired Student's t-test.
Smoking (n (%))	8 (29.6)	48 (31.4)	0.868^‡ ‡ Comparison using chi-square test.	0.88 CI 95% [0.41 – 1.90]
Neoplasia (n (%))	2 (6.9)	27 (16.9)	0.264^‡ ‡ Comparison using chi-square test.	0.38 CI 95% [0.10 – 1.52]
Chronic liver disease (n (%))	3 (10.3)	10 (6.3)	0.640^‡ ‡ Comparison using chi-square test.	1.45 CI 95% [0.51 – 4.16]
Autoimmune diseases (n (%))	2 (7.1)	4 (2.5)	0.484^‡ ‡ Comparison using chi-square test.	2.32 CI 95% [0.71 – 7.60]
Immunological diseases (n (%))	3 (10.3)	12 (7.5)	0.780^‡ ‡ Comparison using chi-square test.	1.25 CI 95% [0.43 – 3.67]
Chronic hematological disease (n (%))	1 (3.4)	5 (3.1)	0.635^‡ ‡ Comparison using chi-square test.	1.10 CI 95% [0.18 – 6.81]
Chronic neurological disease (n (%))	9 (31.0)	16 (9.9)	0.005^‡ ‡ Comparison using chi-square test.	2.87 CI 95% [1.48 – 5.59]
Previous heart failure (n (%))	8 (27.6)	21 (12.9)	0.067^‡ ‡ Comparison using chi-square test.	1.82 CI 95% [0.89 – 3.70]
Other comorbidities (n (%))^† † Other comorbidities included alcoholism, ex-smoking, Alzheimer's disease, rheumatoid arthritis and vasculitis, cerebrovascular disease, dementia, depression, dyslipidemia, gout, hypothyroidism, osteoporosis, peripheral arterial disease, aortic aneurysm, history of deep vein thrombosis.	18 (64.3)	75 (48.7)	0.145^‡ ‡ Comparison using chi-square test.	1.57 CI 95% [0.77 – 3.21]
Number of comorbidities before admission^* * mean ± SD.	4.1 ± 1.4	3.4 ± 1.7	0.005^¶ ¶ Comparison using the Mann-Whitney test.
ACEI/ARB (n (%))	18 (62.1)	94 (58.0)	0.608^‡ ‡ Comparison using chi-square test.	1.08 CI 95% [0.54 – 2.15]
Metformin (n (%))	5 (17.2)	31 (19.1)	0.994^‡ ‡ Comparison using chi-square test.	0.87 CI 95% [0.36 – 2.13]
Simvastatin (n (%))	11 (37.9)	58 (36.0)	0.709^‡ ‡ Comparison using chi-square test.	1.01 CI 95% [0.51 – 2.02]
NSAID (n (%))	2 (8.0)	5 (3.3)	0.533^‡	1.83 CI 95% [0.53 – 6.26]
Number of medications before admission^* * mean ± SD.	3.6 ± 2.6	3.1 ± 3.0	0.186^¶ ¶ Comparison using the Mann-Whitney test.
Lawton scale before admission^* * mean ± SD.	15.8 ± 9.0	18.0 ± 9.3	0.099^¶ ¶ Comparison using the Mann-Whitney test.
SOFA score before admission^* * mean ± SD.	5.6 ± 4.2	4.4 ± 3.9	0.013^¶ ¶ Comparison using the Mann-Whitney test.
SAPS3 score before admission^* * mean ± SD.	60.6 ± 28.1	54.9 ± 29.1	0.037^¶ ¶ Comparison using the Mann-Whitney test.
Lung involvement >=50% upon admission (n (%))	16 (55.2)	78 (48.1)	0.483^‡ ‡ Comparison using chi-square test.	1.18 CI 95% [0.06 – 2.32]^† † Other comorbidities included alcoholism, ex-smoking, Alzheimer's disease, rheumatoid arthritis and vasculitis, cerebrovascular disease, dementia, depression, dyslipidemia, gout, hypothyroidism, osteoporosis, peripheral arterial disease, aortic aneurysm, history of deep vein thrombosis.

Variables	NOAF (n=29)	Non-NOAF (n=162)	p value	RR for NOAF
Fever (n (%))	23 (79.3)	108 (66.7)	0.243	1.69 CI 95% [0.73 – 3.94]
Cough (n (%))	15 (51.7)	111 (68.5)	0.115	0.53 CI 95% [0.27 – 1.03]
Dysosmia (n (%))	4 (13.8)	12 (7.4)	0.436	1.75 CI 95% [0.70 – 4.40]
Dysgeusia (n (%))	1 (3.4)	6 (3.7)	0.778	0.82 CI 95% [0.13 – 5.18]
Asthenia (n (%))	11 (37.9)	70 (43.2)	0.689	0.80 CI 95% [0.40 – 1.60]
Myalgia (n (%))	13 (44.8)	37 (22.8)	0.025	2.20 CI 95% [1.14 – 4.25]
Rhinorrhea (n (%))	4 (13.8)	15 (9.3)	0.679	1.45 CI 95% [0.56 – 3.72]
Dyspnea (n (%))	28 (96.6)	141 (87.0)	0.227	3.46 CI 95% [0.50 – 24.19]
Oxygen Saturation < 94% (n (%))	27 (93.1)	147 (90.7)	0.836	1.25 CI 95% [0.33 – 4.82]
Disorientation (n (%))	13 (44.8)	35 (21.6)	0.016	2.28 CI 95% [1.18 – 4.38]
Agitation/Drowsiness pre-hospitalization (n (%))	9 (31.0)	42 (25.9)	0.626	1.17 CI 95% [0.57 – 2.39]
Odynophagia (n (%))	1 (3.4)	9 (5.6)	0.981	0.64 CI 95% [0.10 – 4.26]
Diarrhea (n (%))	1 (3.4)	30 (18.5)	0.081	0.18 CI 95% [0.03 – 1.26]
Nausea (n (%))	1 (3.4)	13 (8.0)	0.628	0.45 CI 95% [0.07 – 3.08]
Vomiting (n (%))	1 (3.4)	13 (8.0)	0.628	0.45 CI 95% [0.07 – 3.08]
Headache (n (%))	2 (6.9)	17 (10.5)	0.795	0.67 CI 95% [0.17 – 2.60]
Syncope (n (%))	2 (6.9)	6 (3.7)	0.779	1.69 CI 95% [0.48 – 5.88]
Hypotension (n (%))	1 (3.4)	13 (8.0)	0.623	0.45 CI 95% [0.07 – 3.06]

Variables	NOAF (n=29)	Non-NOAF (n=162)	p value	OR for NOAF
CIU admission (n (%))	28 (96.6)	80 (49.4)	<0.001	27.01 CI 95% [3.59 – 203.28]
Mechanical ventilation (n (%))	24 (82.8)	53 (32.7)	<0.001	90.2 CI 95% [3.26 – 24.96]
Hemodialysis (n (%))	10 (34.5)	32 (19.8)	0.116	1.90 CI 95% [0.81 – 4.48]
Time from onset of symptoms to date of hospital admission (days)^* * mean ± SD.	7.6 ± 4.3	8.5 ± 5.1	0.380
Total length of hospital stay (days)^* * mean ± SD.	30.5 ± 27.6	16.2 ± 12.4	0.010
Length of stay in ICU (days)^* * mean ± SD.	11.1 ± 10.5	4.9 ± 7.5	0.004
Time from hospital stay to start of mechanical ventilation (days)^* * mean ± SD.	7.6 ± 9.2	4.2 ± 5.1	0.101
Length in mechanical ventilation (days)^* * mean ± SD.	12.9 ± 14.0	9.5 ± 5.9	0.008
Time from hospitalization to the first episode of AF (days)^* * mean ± SD.	13.7 ± 14.0	-	-
Norepinephrine (n (%))	27 (93.1)	60 (37.0)	<0.001	22.95 CI 95% [5.27 – 99.95]
Chloroquine / Hydroxychloroquine (n (%))	13 (44.8)	42 (25.9)	0.042	2.32 CI 95% [1.03 – 5.23]
Glucocorticoid use (n (%))	23 (79.3)	66 (40.7)	<0.001	5.58 CI 95% [2.15 – 14.44]
Heparin (unfractionated or low molecular weight) (n (%))	26 (89.7)	139 (86.5)	0.628	1.37 CI 95% [0.38 – 4.92]
Ivermectin (n (%))	11 (37.9)	44 (27.2)	0.241	1.64 CI 95% [0.72 – 3.74]

Variables	NOAF (n=29)	Non-NOAF (n=162)	p value	OR for NOAF
Disseminated intravascular coagulation (n (%))	0 (0)	1 (0,6)	0,327
Deep vein thrombosis (n (%))	1 (3,6)	5 (3,1)	0,653
Pulmonary thromboembolism (n (%))	0 (0)	3 (1,9)	0,654
Hospital pulmonary infection (n (%))	15 (51,7)	62 (39,2)	0,259
Hospital infection of any non-pulmonary nature (n (%))	13 (44,8)	24 (14,8)	<0,001	4,67 CI 95% [1,79 – 6,40]
Delirium (n (%))	6 (20,7)	42 (25,9)	0,579
Left ventricular dysfunction (n (%))	16 (55,2)	90 (55,6)	0,842	0,83 CI 95% [0,37 – 1,84]
Shock (n (%))	18 (62,1)	44 (27,2)	<0,001	4,39 CI 95% [1,92 – 10,03]

Variables^† † mean ± SD.	NOAF (n=29)	Non-NOAF (n=162)	p value	RR for NOAF
D-dimer (ng.mL^-1)^† † mean ± SD.	6181.9 ± 15112.2	5120.4 ± 11443.3	0.723
LDH (U.L^-1)^† † mean ± SD.	383.0 ± 194.4	448.8 ± 251.7	0.199
HTO (%)^† † mean ± SD.	36.3 ± 5.7	35.8 ± 6.9	0.736
HGB (g.dL^-1)^† † mean ± SD.	12.1 ± 1.9	11.8 ± 2.5	0.469
WBC (cels.μL^-1)^† † mean ± SD.	6726.2 ± 2894.0	9482.4 ± 10398.1	0.005	2.63 IC 95% [1.18–5.86]
LYNPH (%)^† † mean ± SD.	13.7 ± 8.4	15.4 ± 11.0	0.418
PLA (cels.μL^-1)^† † mean ± SD.	188.1 ± 96.9	252.4 ± 116.7	0.006	4.15 IC 95% [1.94–8.88]
GOT (U.L^-1)^† † mean ± SD.	38.4 ± 19.6	59.0 ± 111.8	0.036	2.45 IC 95% [1.20–5.02]
GPT (U.L^-1)^† † mean ± SD. ^* * Mann-Whitney comparative test.	30.3 ± 15.2	43.4 ± 56.8	0.224
GGT (U.L^-1)^† † mean ± SD. ^* * Mann-Whitney comparative test.	107.4 ± 86.6	139.2 ± 168.8	0.193
URE (mg.dL^-1)^† † mean ± SD.	60.5 ± 48.0	60.8 ± 49.3	0.979
FER (pmol.L^-1)^† † mean ± SD. ^* * Mann-Whitney comparative test.	1611.2 ± 1225.8	2005.7 ± 3087.3	0.328
CRE (mg.dL^-1)^† † mean ± SD.	1.4 ± 1.0	1.8 ± 2.0	0.162
Tn I (>0,2 ng.mL^-1)	30.2 %	12.2 %	0.038	2.46 IC 95% [1.07–5.69]
FIB (mg.dL^-1)^† † mean ± SD.	537.8 ± 270.8	480.5 ± 200.3	0.264
INR (AU)^† † mean ± SD.	1.3 ± 0.2	1.2 ± 0.2	0.111
NT-pro-BNP (pg.mL^-1)^† † mean ± SD.	3884.0 ± 8619.2	5172.2 ± 8659.4	0.602
PTN C R (mg.L^-1)^† † mean ± SD.	85.1 ± 88.6	58.2 ± 52.6	0.128
BAST (absolute count)^† † mean ± SD.	92.0 ± 254.1	181.2 ± 657.3	0.205
PTT (seconds)^† † mean ± SD.	31.3 ± 9.9	29.3 ± 5.9	0.300
K (mEq.L^-1)^† † mean ± SD.	4.5 ± 0.9	4.4 ± 0.8	0.538
NA (mEq.L^-1)^† † mean ± SD.	136.7 ± 5.9	139.8 ± 6.8	0.019	2.51 IC 95% [1.26–5.01]
BIL (mg.dL^-1)^† † mean ± SD.	0.7 ± 0.4	0.7 ± 0.8	0.560
GLU (mg.dL^-1)^† † mean ± SD.	171.5 ± 111.8	156.5 ± 120.1	0.576
PTN (g.dL^-1)^† † mean ± SD.	5.9 ± 0.7	6.4 ± 1.4	0.042	2.75 IC 95% [1.33–5.68]
ALB (g.dL^-1)^† † mean ± SD.	2.8 ± 0.6	3.1 ± 0.6	0.089
CPK (U.L^-1)^† † mean ± SD.	179.5 ± 243.5	223.3 ± 528.8	0.526
TRI (mg.dL^-1)^† † mean ± SD. ^* * Mann-Whitney comparative test.	140.2 ± 51.0	156.4 ± 76.0	0.751
COL (mg.dL^-1)^† † mean ± SD.	150.2 ± 38.3	144.7 ± 46.3	0.578
HDL (mg.dL^-1))^† † mean ± SD. ^* * Mann-Whitney comparative test.	32.0 ± 6.4	34.9 ± 13.7	0.947
LDL (mg.dL^-1)^† † mean ± SD.	93.2 ± 32.2	86.5 ± 41.2	0.459
GFR CKD-EP (ml/min)^† † mean ± SD.	79.0 ± 20.8	82.8 ± 25.7	0.460

	Univariate Analysis			Univariate Analysis
	β	HR CI 95%	p value	β	HR CI 95%	p value	Score
Age > 71 years	1.200	3.3 [1.5 – 7.3]	0.003	1.913	6.8 [2.5 – 18.3]	<0.001	1
Number of comorbidities > 4	0.840	2.3 [1.1 – 4.8]	0.024
Neurological disease	1.150	3.2 [1.4 – 7.0]	0.005
Disorientation	1.179	3.3 [1.5 – 6.9]	0.002	0.919	2.5 [1.05 – 6.0]	0.04	1
Myalgia	1.007	2.7 [1.3 – 5.7]	0.007
Nosocomial infection	1.025	2.8 [1.3 – 5.8]	0.007
Shock	1.178	3.2 [1.5 – 7.0]	0.003
Mechanical ventilation	1.902	6.7 [2.6 – 17.5]	<0.001
ICU admission	2.891	18.0 [8.5 – 131.5]	0.005
Troponin > 0,2 ng.mL^-1	0.651	1.9 [0.8 – 4.8]	0.170
Noradrenaline use	2.622	13.8 [3.3 – 57.8]	<0.001
SAPS3 > 55	1.173	3.2 [1.3 – 8.1]	0.013	1.723	5.6 [1.9 – 16.6]	0.002	1
Total leukocyte count ≤ 7.720 cels.μL^-1	1.170	3.2 [1.4 – 7.6]	0.008	1.887	6.6 [2.2 – 19.9]	<0.001	1
Platelets < 196.000 cels.μL^-1	1.503	4.5 [2.0 – 10.1]	<0.001
GOT < 37 U.L^-1	0.986	2.7 [1.2 – 5.8]	0.014
Natremia < 137 mEq.L^-1	0.836	2.3 [1.1 – 4.9]	0.030	1.611	5.0 [1.9 – 13.1]	0.001	1
Total proteins < 6 g.dL^-1	1.247	3.5 [1.5 – 8.0]	0.004
Optimal cut-off value	Specificity (%)^§ § [CI 95].	Sensitivity(%)^§ § [CI 95].	AUC^§ § [CI 95].	p-value^† † Cox function adjusted p-value < 0,001; χ2 15,0; r2=0,927;	HR^‡ ‡ N=135; ^§ § [CI 95].
> 2	65.2 [57.3 – 72.5]	82.8 [64.2 – 94.1]	0.815 [0.717 – 0.913]	<0.001	7.6 [2.9 – 19.8]

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