Determinants of Visceral Infarction in Acute Cardioembolic Stroke Due to Atrial Fibrillation

Article information

J Stroke. 2021;23(2):277-280
Publication date (electronic) : 2021 May 31
doi : https://doi.org/10.5853/jos.2020.03972
aDepartment of Neurology, Keimyung University Dongsan Hospital, Keimyung University School of Medicine, Daegu, Korea
bDepartment of Neurology, Daegu Fatima Hospital, Daegu, Korea
cDepartment of Radiology, Semyung Radiology Clinic, Gumi, Korea
dDepartment of Neurology and Neurosurgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
Correspondence: Jeong-Ho Hong Department of Neurology, Keimyung University Dongsan Hospital, Keimyung University School of Medicine, 1035 Dalgubeol-daero, Dalseo-gu, Daegu 42601, Korea Tel: +82-53-258-7839 Fax: +82-53-258-4380 E-mail: neurohong79@gmail.com
*These authors contributed equally to the manuscript as first author.
Received 2020 September 20; Revised 2020 December 21; Accepted 2020 December 28.

Dear Sir:

Atrial fibrillation (AF) is associated with an increased risk of systemic embolism and cardioembolic stroke. However, research on coexisting subdiaphragmatic visceral infarctions (SDVIs) with acute ischemic stroke due to AF is scarce. The most frequent localization of SDVI is the kidneys [1]. Acute kidney injury following acute renal infarction can occur in 20% to 40% cases, and chronic kidney injury, in about 34% of cases [2]. Splenic infarction was the second most common SDVI in AF-related acute ischemic stroke, with a 5% mortality rate [3]. Acute mesenteric ischemia is an infrequent event, though with high mortality risk [4]. SDVI diagnosis is frequently missed or delayed because of nonspecific clinical symptoms. Therefore, it is essential to predict coexisting acute SDVI in AF-related stroke patients.

Patients with acute cardioembolic stroke due to nonvalvular AF within 7 days of the onset of symptoms were prospectively included at two tertiary hospitals between April 2016 and February 2018. All subjects were examined using abdominal magnetic resonance imaging (MRI) and transthoracic echocardiography (TTE) within 7 days of onset. Detailed criteria of subjects and MRI protocols were described in the Supplementary methods [5] and Supplementary Figure 1.

A total of 100 consecutive nonvalvular AF-related acute cardioembolic stroke patients were enrolled. The median age was 74 years (interquartile range, 68 to 79), and 47% were male. Among those patients, acute and chronic SDVIs occurred in 31 (31%) patients. Comparisons of baseline characteristics between each group are shown in Table 1. One patient had acute and chronic SDVI simultaneously. Twenty-three acute coexisting SVDIs were found in 20 patients (20%): 20 cases of renal infarction (Supplementary Figure 2), two splenic infarction, and one mesenteric infarction due to superior mesenteric artery occlusion. Of the 20 patients with acute renal infarction, four had an acute infarction in both kidneys. Furthermore, 12 patients had previous chronic SDVIs (10 with renal, two splenic infarction). One patient had chronic renal infarction on both sides. No hepatic infarction was shown (Supplementary Table 1). In 96 patients with available TTE data, the rate of moderate to severe left atrial enlargement (LAE), defined as volume/body surface area ≥42 mL/m², was 69.8%.

Baseline characteristics in patients with acute cardioembolic stroke due to atrial fibrillation

In the multiple logistic regression model, moderate to severe LAE was significantly associated with the coexistence of acute SDVIs in patients with acute ischemic stroke due to AF (adjusted odds ratio [aOR], 11.40; 95% confidence interval [CI], 1.29 to 100.97; P=0.03), and also a significant determinant for the presence of all SDVIs stages (aOR, 5.12; 95% CI, 1.37 to 19.15; P=0.02) (Table 2).

Independent predictors associated with subdiaphragmatic visceral infarction

Our study found that 31% of patients with acute cardioembolic stroke attributed to AF, presenting within 7 days of onset, showed some stage of SVDI. Acute coexisting SVDIs occurred in 20% of total cases and chronic SDVIs in 12%. In one postmortem study, SDVI was observed in 38.6% of patients with cardioembolic stroke [1]. However, this study had a potential for selection bias (only fatal strokes were included), and it could not assess the temporal link between acute cardioembolic stroke due to AF and concomitant acute SDVIs.

Abdominal MRI, including diffusion-weighted imaging, can easily differentiate between recent and old infarctions, and we performed an abdominal MRI within 7 days of symptom onset. Furthermore, there is no additional harm to patients suspected of accompanying acute renal infarction due to no need to use contrast agents compared to abdominal computed tomography. However, there is a limit to the implementation in patients with unstable vital signs. In a small MRI-based study, four (14.8%) out of 27 stroke patients with AF showed recent infarctions and three (11.1%) old infarctions [6]. Another MRIbased study found SDVIs in 10 (21.3%) out of 47 patients with ischemic stroke due to AF [7]. Of those, 10.7% had acute and 10.6% chronic infarctions. In terms of acute SDVIs, our study showed a higher incidence than previous studies. This finding may be due to a higher rate of vascular comorbidities and a higher risk of the CHA2DS2-VASc score in our subjects. The prevalence of chronic SDVIs was similar to previous MRI-based studies.

Our results suggest that a moderate-to-severe LAE on TTE is more closely related to a greater risk of acute coexisting SDVIs, in acute cardioembolic stroke due to AF, compared to normal left atrium (LA) or mild LAE, which were independent of the SDVI stage. Atrial remodeling and impaired atrial contractility may contribute to LAE, which in turn may lead to more blood stasis and endothelial injury, thereby predisposing to thromboembolism. Thrombus formation is more likely to occur in the larger LA. Large LA volume could be a good predictor of an increased risk of ischemic stroke, systemic embolism, and mortality in AF patients without a history of previous stroke [8]. The association between LAE and recurrent stroke is already well known. However, before our study, the association between LAE and systemic embolism in AF-related acute cardioembolic stroke was less clear. Based on our results, evaluating the coexistence of acute SDVIs is critical in AF-related acute cardioembolic stroke patients with moderate-to-severe LAE.

The interpretation of our results require caution because of selection bias. In contrast to the autopsy study, some patients with unstable vital signs or malignant stroke may have been excluded from the study. Non-categorization of AF type is also considered an important limitation. However, LA volume is positively correlated with AF duration and could be a good marker of AF duration.

Supplementary materials

Supplementary materials related to this article can be found online at https://doi.org/10.5853/jos.2020.03972.

Supplementary methodsjos-2020-03972-suppl1.pdf
Supplementary Table 1.

Localization of subdiaphragmatic visceral infarction

jos-2020-03972-suppl2.pdf
Supplementary Figure 1.

Flow diagram of study participants. SU, stroke unit; SDVI, subdiaphragmatic visceral infarction.

jos-2020-03972-suppl2.pdf
Supplementary Figure 2.

Abdominal diffusion-weighted imaging (A) with the apparent diffusion coefficient (B) of 72-year-old patient, showing an area of acute renal infarction in the lower pole of the right kidney (arrows).

jos-2020-03972-suppl3.pdf

Notes

The authors have no financial conflicts of interest.

References

1. Abboud H, Labreuche J, Gongora-Riverra F, Jaramillo A, Duyckaerts C, Steg PG, et al. Prevalence and determinants of subdiaphragmatic visceral infarction in patients with fatal stroke. Stroke 2007;38:1442–1446.
2. Kwon JH, Oh BJ, Ha SO, Kim DY, Do HH. Renal complications in patients with renal infarction: prevalence and risk factors. Kidney Blood Press Res 2016;41:865–872.
3. Nores M, Phillips EH, Morgenstern L, Hiatt JR. The clinical spectrum of splenic infarction. Am Surg 1998;64:182–188.
4. Schoots IG, Koffeman GI, Legemate DA, Levi M, van Gulik TM. Systematic review of survival after acute mesenteric ischaemia according to disease aetiology. Br J Surg 2004;91:17–27.
5. Ko Y, Lee S, Chung JW, Han MK, Park JM, Kang K, et al. MRI-based algorithm for acute ischemic stroke subtype classification. J Stroke 2014;16:161–172.
6. Slaoui T, Klein IF, Guidoux C, Cabrejo L, Meseguer E, Abboud H, et al. Prevalence of subdiaphragmatic visceral infarction in cardioembolic stroke. Neurology 2010;74:1030–1032.
7. Weisenburger-Lile D, Lopez D, Russel S, Kahn JE, Veiga Hellmann A, Scherrer A, et al. IRMA study: prevalence of subdiaphragmatic visceral infarction in ischemic stroke and atrial fibrillation. Int J Stroke 2017;12:421–424.
8. Hamatani Y, Ogawa H, Takabayashi K, Yamashita Y, Takagi D, Esato M, et al. Left atrial enlargement is an independent predictor of stroke and systemic embolism in patients with non-valvular atrial fibrillation. Sci Rep 2016;6:31042.

Article information Continued

Table 1.

Baseline characteristics in patients with acute cardioembolic stroke due to atrial fibrillation

Characteristic Total (n=100) Acute SDVI (n=20) No acute SDVI (n=80) P SDVI (n=31) No SDVI (n=69) P
Age (yr) 74 (68–79) 73 (67–77) 75 (69–79) >0.999 73 (68–77) 75 (69–79) 0.478
Male sex 47 (47) 10 (50) 37 (46.3) 0.764 13 (41.9) 34 (49.3) 0.643
BMI (kg/m2) 23.6 (20.6–26.1) 23.8 (22.1–25.2) 23.4 (20.3–26.2) 0.782 23.8 (22.0–26.0) 23.3 (20.2–26.1) 0.357
Previous stroke 25 (25) 5 (25) 20 (25) >0.999 9 (29.0) 16 (23.2) 0.708
Onset-to-ER visit time (hr) 8.2 (2.1–22.2) 4.3 (2.2–22.5) 8.9 (2.0–22.2) 0.508 3.5 (2.1–13.3) 9.9 (2.1–22.5) 0.336
Vascular risk factors
 Hypertension 62 (62) 13 (65) 49 (61.3) 0.757 21 (67.7) 41 (59.4) 0.569
 Diabetes mellitus 29 (29) 5 (25) 24 (30) 0.659 10 (32.3) 19 (27.5) 0.808
 Hypercholesterolemia 24 (24) 5 (25) 19 (23.8) >0.999 10 (32.3) 14 (20.3) 0.297
 Ischemic heart disease 12 (12) 1 (5) 11 (13.8) 0.451 3 (9.7) 9 (13.0) 0.884
 Current smoking 16 (16) 3 (15) 13 (16.3) >0.999 3 (9.7) 13 (18.8) 0.389
CHA2DS2-VASc score 5 (4–6) 5 (4–6) 5 (4–6) 0.338 5 (4–6) 5 (4–6) 0.948
Initial NIHSS score 4 (1-9) 3 (1 -14) 4 (1–8) 0.506 3 (1–8) 4 (1–9) 0.211
Previous medication history
 Anticoagulant treatment 20 (20) 4 (20) 16 (20) >0.999 5 (16.1) 15 (21.7) 0.705
 Antiplatelet treatment 43 (43) 10 (50) 33 (41.3) 0.480 16 (51.6) 27 (39.1) 0.343
 Statin use 19 (19) 4 (20) 15 (18.8) >0.999 7 (22.6) 12 (17.4) 0.737
Acute treatment 15 (15) 4 (20) 11 (13.8) 0.493 7 (22.6) 8 (11.6) 0.155
 Intravenous tPA 11 (11) 3 (15) 8 (10) 0.689 5 (16.1) 6 (8.7) 0.451
 Endovascular treatment 8 (8) 3 (15) 5 (6.3) 0.196 4 (5.8) 4 (12.9) 0.416
Imaging findings
 Major vessel occlusion 29(29) 6(30) 23(28.8) >0.999 9 (29.0) 20 (29.0) >0.999
 Multiple vascular territories 22 (22) 4 (20) 18 (22.5) >0.999 8 (25.8) 14 (20.3) 0.723
 Multiple scattered lesion 68 (68) 13 (65) 55 (68.8) 0.748 20 (64.5) 48 (69.6) 0.788
 Posterior circulation lesion 30 (30) 7 (35) 23 (28.7) 0.585 13 (41.9) 17 (24.6) 0.081
Chronic visceral infarction 12 (12) 1 (5) 11 (13.8) 0.451
Onset-to-abdominal MRI time (day) 3.68 (2.14–5.13) 3.91 (2.55–5.46) 3.63 (2.01–4.92) 0.251 3.40 (2.16 – 5.32) 3.71 (2.11–4.91) 0.834
TTE findings (n/N)
 Ejection fraction 64 (52–65), 84/100 60 (53.4–63.8), 18/20 61 (52–65.5), 66/77 0.496 60 (53–66), 29/31 61 (52–66), 66/69 0.952
 Diastolic dysfunction (E/e’ >15) 24 (27.3), 86/100 4 (25), 16/20 20 (27.8), 72/80 >0.999 7 (26.9), 26/31 17 (27.4), 62/69 >0.999
 LAVI (mL/m2) 56.1 (39–83.2), 96/100 68.2 (49.4–92.7), 18/20 53.4 (38.0–81.4), 78/80 0.117 62.1 (46.9–93.8), 29/31 51.7 (38.0–81.2), 67/69 0.092
 Moderate to severe LAE (42 mL/m²≥ LAVI) 67/96 (69.8), 96/100 17/18 (94.4), 18/20 50/78 (64.1), 78/80 0.012 26/29 (89.7), 29/31 41/67 (61.2), 67/69 0.005

Values are presented as median (interquartile range) or number (%).

SDVI, subdiaphragmatic visceral infarction; BMI, body mass index; ER, emergency room; CHA2DS2-VASc, congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65–74 years, sex category; NIHSS, National Institutes of Health Stroke Scale; tPA, tissue plasminogen activator; MRI, magnetic resonance imaging; TTE, transthoracic echocardiography; n, the total number of patients with available data; N, the total number of patients; LAVI, left atrial volume index; LAE, left atrial enlargement.

Table 2.

Independent predictors associated with subdiaphragmatic visceral infarction

Variable OR 95% CI P
Acute subdiaphragmatic visceral infarction
 Age (yr) 0.999 0.941–1.061 0.979
 Male sex 0.806 0.248–2.615 0.719
 Endovascular treatment 1.874 0.363–9.681 0.454
 Moderate to severe LAE 11.401 1.287–100.965 0.029
 Onset-to-abdominal MRI time (day) 1.272 0.965–1.676 0.088
Acute and chronic subdiaphragmatic visceral infarction
 Age (yr) 0.999 0.945–1.055 0.964
 Male sex 1.270 0.468–3.446 0.638
 Initial NIHSS score 0.965 0.885–1.052 0.419
 Posterior circulation lesion 2.036 0.728–5.691 0.175
 Acute treatment 2.275 0.585–8.853 0.236
 Moderate to severe LAE 5.123 1.370–19.149 0.015

OR, odds ratio; CI, confidence interval; LAE, left atrial enlargement; MRI, magnetic resonance imaging; NIHSS, National Institutes of Health Stroke Scale.