Clinical characteristics of the study participants
The mean fasting blood sugar was 6.6 (SD 3.9) for cases and 5.3 (SD 0.7) for controls. This was statistically significant with a p value of 0.015. Waist to hip ratio was also statistically significant with a p value of 0.007. Cases with an elevated wait to hip ratio were 14 (27.5%) and controls were 3 (5.9%). Table Table2 2 shows the baseline clinical characteristics of the study participants.
| | ||
---|---|---|---|
Systolic blood pressure | 134.3 (31.9) | 129.0 (22.3) | 0.339 |
Diastolic blood pressure | 85.0 (22.4) | 80.5 (18.7) | 0.274 |
Fasting blood sugar | 6.6 (3.9) | 5.3 (0.7) | |
Yes | 21 (41.2) | 13 (25.5) | 0.093 |
No | 30 (58.8) | 38 (74.5) | |
High | 6 (12.0) | 1 (2.0) | 0.060 |
Normal | 44 (88.0) | 50 (98.0) | |
Yes | 14 (27.5) | 8 (15.7) | 0.149 |
No | 37 (72.6) | 43 (84.3) | |
Yes | 16 (31.4) | 18 (35.3) | 0.674 |
No | 35 (68.6) | 33 (64.7) | |
Yes | 2 (4.8) | 0 (0.0) | 0.495 |
No | 49 (96.1) | 51 (100.0) | |
Yes | 4 (7.8) | 8 (15.7) | 0.357 |
No | 47 (92.2) | 43 (84.3) | |
Yes | 2 (3.9) | 0 (0.0) | 0.495 |
No | 49 (96.1) | 51 (100.0) | |
High | 14 (27.5) | 3 (5.9) | |
Normal | 37 (72.6) | 48 (94.1) |
Laboratory characteristics of the study participants
HIV serology and Hb electrophoresis were statistically significant with a p value of 0.076 and 0.023 respectively. 18 patients (35.3%) were reactive for HIV among cases and controls 10 (19.6%). 12 patients (23.5%) had abnormal Hb electrophoresis among cases controls 3 (5.9%). Table Table3 3 shows the laboratory characteristics of the study participants.
| | ||
---|---|---|---|
Normal | 40 (78.4) | 44 (86.3) | 0.299 |
Low/high | 11 (21.6) | 7 (13.7) | |
Normal | 42 (82.4) | 43 (84.3) | 0.790 |
Low/high | 9 (17.7) | 8 (15.7) | |
Normal | 44 (86.3) | 48 (94.1) | 0.318 |
Low/high | 7 (13.7) | 3 (5.9) | |
Normal | 37 (72.6) | 38 (74.5) | 0.822 |
Low/high | 14 (27.5) | 13 (25.5) | |
Normal | 29 (56.9) | 30 (58.8) | 0.841 |
Low/high | 22 (43.1) | 21 (41.2) | |
Normal | 37 (72.6) | 40 (78.4) | 0.490 |
Low/high | 14 (27.5) | 11 (21.6) | |
Normal | 38 (74.5) | 40 (78.4) | 0.641 |
Low/high | 13 (25.5) | 11 (21.6) | |
Reactive | 5 (9.8) | 5 (9.8) | > 0.999 |
Non-reactive | 46 (90.2) | 46 (90.2) | |
Non-Reactive | 33 (64.7) | 41 (80.4) | |
Reactive | 18 (35.3) | 10 (19.6) | |
AA | 39 (76.5) | 48 (94.1) | |
SS | 12 (23.5) | 3 (5.9) |
Stroke types by social demographic characteristics of cases.
Among 62 patients, who had brain CT scan done, 11 patients had non stroke pathologies (4 had brain abscesses, 7 patients had ring enhancing lesions suggestive of toxoplasmosis). Among 51 patients with stroke confirmed on CT scan, the frequency of ischemic stroke was 76.5% and hemorrhagic stroke was 23.5%.
Most participants with ischemic or hemorrhagic stroke were in the age group 36–45 years. Females predominated in both ischemic and hemorrhagic stroke. Details of the social demographic characteristics by stroke types are shown in Table Table4 4 .
Social demographic characteristics by stroke types
| | ||
---|---|---|---|
Overall | 39 (76.5) | 12 (23.5) | |
18–25 | 4 (10.3) | 1 (8.3) | > 0.999 |
26–35 | 10 (25.6) | 3 (25.0) | |
36–45 | 25 (64.1) | 8 (66.7) | |
Male | 17 (43.6) | 5 (41.7) | 0.906 |
Female | 22 (56.4) | 7 (58.3) | |
Protestant | 18 (46.2) | 5 (41.7) | 0.222 |
Catholic | 8 (20.5) | 6 (50.0) | |
Moslem | 9 (23.1) | 1 (8.3) | |
Other | 4 (10.3) | 0 (0.0) | |
Married | 23 (59.0) | 9 (75.0) | 0.721 |
Never married (single) | 8 (20.5) | 2 (16.7) | |
Married before | 8 (20.5) | 1 (8.3) | |
Primary | 17 (43.6) | 5 (41.7) | 0.887 |
Secondary | 11 (28.2) | 5 (41.7) | |
Tertiary | 4 (10.3) | 1 (8.3) | |
Never attended school | 7 (18.0) | 1 (8.3) |
Majority of patients with hemorrhagic stroke were hypertensive (91.7%) compared to only 25.6% among patients with ischemic stroke. Details of the clinical and laboratory characteristics of the study participants by stroke subtypes are shown in Table Table5 5 .
Shows the clinical and laboratory characteristics by stroke types
| | ||
---|---|---|---|
Hypertensive (Yes) | 10 (25.6) | 11 (91.7) | > 0.001 |
High | 4(10.5) | 2(16.7) | 0.621 |
Normal | 34(89.5) | 10(83.3) | |
High | 13(33.3) | 1(8.33) | 0.142 |
Normal | 26(66.7) | 11(91.7) | |
1(2.56) | 0(0.00) | > 0.999 | |
8(20.5) | 3(25.0) | 0.706 | |
3(13.0) | 4(57.4) | 0.033 | |
Normal | 29(74.4) | 8(72.6) | 0.715 |
Low/high | 10(25.6) | 4(33.3) | |
Normal | 23(59.0) | 6(50.0) | 0.583 |
Low/high | 16(41.0) | 6(50.0) | |
Normal | 29 (74.7) | 9(75.0) | > 0.999 |
Low/high | 10(25.6) | 3(25.0) | |
Reactive | 16(41.0) | 2(16.7) | 0.174 |
Non-reactive | 23(59.0) | 10(83.3) | |
AA | 30(77.0) | 9(75.0) | > 0.999 |
SS | 9(23.1) | 3(25.0) |
Social demographic characteristics at univariate analysis
Oral contraceptive use showed a significant difference with an unadjusted OR of 0.27 (95% CI 0.08–0.87) case subjects 23.3% and control subjects 56.5%. Belonging to other religion (seventh day advent, Pentecostal) was statistically significant with a p value of 0.009, OR 0.17. These findings are detailed in Table Table6 6 below.
| | | ||
---|---|---|---|---|
Mean (SD) | 36.8 (7.4) | 36.8 (6.9) | ||
18–25 | 5 (9.8) | 4 (7.8) | ||
26–35 | 13 (25.5) | 17 (33.3) | ||
36–45 | 33 (64.7) | 30 (58.8) | ||
Male | 22 (43.1) | 24 (47.1) | ||
Female | 29 (56.9) | 27 (52.9) | ||
Protestant | 23 (45.1) | 14 (27.5) | Reference | |
Catholic | 14 (27.5) | 17 (33.3) | 0.44 (0.16 – 1.20) | 0.110 |
Moslem | 10 (19.6) | 7 (13.7) | 0.71 (0.22 – 2.28) | 0.567 |
Other | 4 (7.8) | 13 (25.5) | 0.17 (0.05 – 0.65) | |
Married | 32 (62.8) | 31 (60.8) | Reference | |
Never married (single) | 10 (19.6) | 12 (23.5) | 0.70 (0.24 – 2.02) | 0.509 |
Married before | 9 (17.7) | 8 (15.7) | 0.88 (0.27 – 2.79) | 0.823 |
Primary | 22 (43.1) | 19 (37.3) | Reference | |
Secondary | 16 (31.4) | 21 (41.2) | 0.58 (0.23 – 1.47) | 0.250 |
Tertiary | 5 (9.8) | 6 (11.8) | 0.62 (0.16 – 2.38) | 0.485 |
Yes | 1 (2.0) | 2 (3.9) | 0.34 (0.03 – 3.95) | 0.390 |
No | 50 (98.0) | 49 (96.1) | Reference | |
Yes | 4 (7.8) | 5 (9.8) | 0.80 (0.19 – 3.30) | 0.755 |
No | 47 (92.2) | 46 (90.2) | Reference | |
Yes | 11 (21.6) | 11 (21.6) | 0.97 (0.38 – 2.48) | 0.946 |
No | 40 (78.4) | 40 (78.4) | Reference | |
Yes | 1 (2.0) | 1 (2.0) | 1.31 (0.08 – 21.07) | 0.849 |
No | 50 (98.0) | 50 (98.0) | Reference | |
Yes | 7 (24.1) | 14 (51.9) | 0.30 (0.09–0.98) | |
No | 22 (75.9) | 13 (48.1) | Reference |
a Obtained accounting for matching by age and sex using a conditional logistic regression
b No comparison made because matching was done using these variables (age and sex)
c Accounting for matching was done only for age because contraceptive use applies only to female gender
There was a significant difference in waist to hip ratio between cases (27.5%) and controls (5.9%), with unadjusted OR 6.85 (CI 1.70–27.62). HIV serology with an unadjusted OR of 2.64 (95% CI 1.03–6.82). Hb electrophoresis with an unadjusted OR of 4.31 (95% CI- 1.15–16.17). Fasting blood sugar with an unadjusted OR of 1.64 (95% CI 1.02–2.62). Details of the above findings are shown in Table Table7 7 below.
Clinical characteristics of study participants at univariate analysis
| | |||
---|---|---|---|---|
| ||||
Systolic blood pressure | 134.3 (31.9) | 129.0 (22.3) | 1.01 (0.99 – 1.02) | 0.397 |
Diastolic blood pressure | 85.0 (22.4) | 80.5 (18.7) | 1.01 (0.99 – 1.03) | 0.319 |
Fasting blood sugar | 6.6 (3.9) | 5.3 (0.7) | 1.64 (1.02 – 2.62) | |
| ||||
Yes | 21 (41.2) | 13 (25.5) | 1.78 (0.77 – 4.12) | 0.175 |
No | 30 (58.8) | 38 (74.5) | Reference | |
High | 6 (12.0) | 1 (2.0) | 5.61 (0.12 – 48.65) | 0.118 |
Normal | 44 (88.0) | 50 (98.0) | Reference | |
Yes | 14 (27.5) | 8 (15.7) | 1.77 (0.66 – 4.75) | 0.257 |
No | 37 (72.6) | 43 (84.3) | Reference | |
Yes | 16 (31.4) | 18 (35.3) | 0.77 (0.34 – 1.75) | 0.537 |
No | 35 (68.6) | 33 (64.7) | Reference | |
Yes | 2 (4.8) | 0 (0.0) | 3.12 (0.24 – 167.1) | 0.308 |
No | 49 (96.1) | 51 (100.0) | Reference | |
Yes | 4 (7.8) | 8 (15.7) | 0.39 (0.10 – 1.44) | 0.156 |
No | 47 (92.2) | 43 (84.3) | Reference | |
Yes | 2 (3.9) | 0 (0.0) | 3.12 (0.24 – 167.1) | 0.308 |
No | 49 (96.1) | 51 (100.0) | Reference | |
High | 14 (27.5) | 3 (5.9) | 6.85 (1.70 – 27.62) | |
Normal | 40 (78.4) | 44 (86.3) | Reference | |
Low/high | 11 (21.6) | 7 (13.7) | 1.63 (0.56 – 4.73) | 0.369 |
Normal | 42 (82.4) | 43 (84.3) | Reference | |
Low/high | 9 (17.7) | 8 (15.7) | 1.17 (0.40 – 3.37) | 0.777 |
Normal | 44 (86.3) | 48 (94.1) | Reference | |
Low/high | 7 (13.7) | 3 (5.9) | 2.58 (0.63 – 10.59) | 0.188 |
Normal | 37 (72.6) | 38 (74.5) | Reference | |
Low/high | 14 (27.5) | 13 (25.5) | 1.07 (0.43 – 2.63) | 0.891 |
Normal | 29 (56.9) | 30 (58.8) | Reference | |
Low/high | 22 (43.1) | 21 (41.2) | 0.97 (0.43 – 2.16) | 0.933 |
Normal | 37 (72.6) | 40 (78.4) | Reference | |
Low/high | 14 (27.5) | 11 (21.6) | 1.41 (0.58 – 3.46) | 0.450 |
Normal | 38 (74.5) | 40 (78.4) | Reference | |
Low/high | 13 (25.5) | 11 (21.6) | 1.32 (0.53 – 3.29) | 0.556 |
Reactive | 5 (9.8) | 5 (9.8) | Reference | |
Non-reactive | 46 (90.2) | 46 (90.2) | 1.04 (0.28 – 3.93) | 0.953 |
Non-Reactive | 33 (64.7) | 41 (80.4) | Reference | |
Reactive | 18 (35.3) | 10 (19.6) | 2.64 (1.03–6.82) | |
AA | 39 (76.5) | 48 (94.1) | Reference | |
SS | 12 (23.5) | 3 (5.9) | 4.31 (1.15 – 16.17) |
b Obtained by adding a 1 on each cell count (due to zero cell count)
c High (male: > 0.95, female > 0.85); Normal (male: < 0.95, female < 0.85)
Risk factors for stroke at multivariate analysis
At multivariate analysis, HIV serology (OR 3.72, 95% CI 1.16–10.96), waist to hip ratio (OR 11.26 95% CI 1.98–68.24) and sickle cell disease OR 4.78 95% CI 1.11–19.70) were independent risk factors for stroke in young adults. Table Table8 8 shows risk factors at multivariate analysis. None of the patients with HIV met the definition of AIDS as defined by the occurrence of any of the more than 20 life-threatening cancers or “opportunistic infections”, by WHO.
| ||||
---|---|---|---|---|
Non−reactive | 33 (64.7) | 41 (80.4) | Reference | 0.025 |
Reactive | 18 (35.3) | 10 (19.6) | 3.72 (1.18–11.75) | |
Normal | 37 (72.6) | 48 (94.1) | Reference | |
High | 14 (27.5) | 3 (5.9) | 11.26 (1.64–77.24) | 0.014 |
AA | 39 (76.5) | 48 (94.1) | Reference | 0.034 |
SS | 12 (23.5) | 3 (5.9) | 4.78 (1.12–20.37) | |
Yes | 4 (7.8) | 8 (15.7) | Reference | 0.047 |
No | 47 (92.2) | 43 (84.3) | 8.48 (1.03–70.11) | |
Protestant | 23 (45.1) | 14 (27.5) | Reference | |
Catholic | 14 (27.5) | 17 (33.3) | 0.44 (0.13–1.51) | 0.194 |
Moslem | 10 (19.6) | 7 (13.7) | 0.53 (0.13–2.23) | 0.390 |
Other | 4 (7.8) | 13 (25.5) | 0.09 (0.01–0.56) | 0.010 |
Normal | 44(88.0) | 50(98.0) | Reference | |
High | 6(12.0) | 1(2.0) | 8.06(0.43–152.78) | 0.164 |
a High (male: > 0.95, female > 0.85); Normal (male: < 0.95, female < 0.85)
b Obtained accounting for matching by age and sex using a conditional logistic regression
Variables with p value < 0.2 included in multivariant analysis include fasting blood sugar, hypertension, family of diabetes mellitus, waist to hip ratio, leucocyte count, HIV serology, sickle cell disease and oral contraceptive use
This case–control study showed that the frequency of ischemic stroke was higher than that of hemorrhagic stroke in young Ugandan population. We showed that positive HIV serology, elevated waist to hip ratio and sickle cell disease were independent risk factors for stroke in this population.
This is consistent with several studies that have been done and found ischemic stroke to be more prevalent than hemorrhagic stroke. Studies done in Africa, in Libya reported 77% ischemic stroke and 23% hemorrhagic stroke (these included both intracerebral and subarachnoid hemorrhagic stroke) [ 14 ], in Morocco, 87.3% ischemic stroke and 12.7% hemorrhagic (study did not specify on the subtypes of hemorrhagic stroke) [ 6 ]. In a study from Bosnia and Herzegovina, Subarachnoid hemorrhage was more frequent in young adults compared with older patients (> 45 years of age) (22% vs. 3.5%), intracerebral hemorrhage (ICH) was similar in both groups (16.9% vs. 15.8%), but ischemic stroke (IS) was predominant stroke type in the older group (61% vs. 74%) [ 15 ]. On the other hand, studies focusing on all young stroke patients and including also subarachnoid hemorrhages have found much higher proportion of hemorrhagic strokes in younger vs. older individuals. Population-based studies have reported as low as 57% prevalence for ischemic stroke in those aged > 45, as reported by a recent narrative review [ 16 ]. This difference in occurrence of stroke subtypes could be due to the low prevalence of hypertension in this population in our setting given that hypertension has been reported to be the commonest risk factor for hemorrhagic stroke.
Most previous studies of HIV and stroke have been retrospective, but the prospective studies in Africa and East Africa have reported the importance of HIV as a risk factor for stroke [ 17 ]. A recently published study done in Malawi, with defined cases and population controls and 99% ascertainment of HIV status, reported HIV infection as an independent risk factor for stroke. This study further found that patients who had started standard HIV treatment in the previous six months had a higher risk of stroke (OR 15.6 95% CI 4.21–46.6). This was probably due to an immune reconstitution inflammatory syndrome (IRIS) like process [ 18 ]. A variety of mechanisms have been implicated in the association of HIV and stroke, these include HIV associated vasculopathy, vasculitis which causes abnormality of the intracranial or extracranial cerebral blood vessels and neoplastic involvement. Indirectly through cardioembolic, coagulopathy in association with protein C and protein S deficiency. Some infections are well established causes of stroke, such as Mycobacterium tuberculosi s , syphilis, and varicella zoster virus through increased susceptibility to acquisition or reactivation of these infections [ 19 , 20 ]. Combined antiretroviral therapy (cART) might unmask occult opportunistic infections that subsequently cause a stroke. This possibility should be considered in all patients who have had an acute stroke or have worsening of stroke symptoms after initiation of cART [ 21 ].
An elevated waist to hip ratio (WHR) was associated with 12 times increased risk of stroke among young adults in Mulago hospital compared to individuals with a normal waist to hip ratio. Abdominal obesity (measured as waist–hip ratio) is associated with an increased risk of myocardial infarction, stroke, and premature death [ 22 ]. This agrees with a few studies that have assessed the association of stroke with waist to hip ratio. Aaron et al. 1990, assessed the relation between body fat distribution, and the 2-year incidences of hypertension and stroke in a cohort of 41,837 women aged 55–69 years. Women who developed stroke were 2.1 (95% CI 1.5–2.9) times more likely to have an elevated ratio than those who did not [ 23 ]. Md Habib et al. 2011 assessed high waist to hip ratio as a risk factor for ischemic stroke for overall stroke and he found 64% of the ischemic stroke patient had abnormal WHR in Bangladesh [ 24 ]. Abdominal obesity measured with WHR was an independent risk factor for cryptogenic ischemic stroke (CIS) in young adults after rigorous adjustment for concomitant risk factors in the Revealing the Etiology, Triggers, and Outcome (SECRETO; NCT01934725) study, a prospective case–control study that included patients aged 18–49 years with a first ever CIS at 19 European university centers [ 25 ].
Sickle cell disease was also associated with increased risk of stroke among young adults in Mulago hospital. This agrees with several studies that have associated sickle cell disease with stroke. Ohene et al. 1998 assessed cerebrovascular accidents (CVA) in sickle cell disease, found the highest rates of prevalence of 4.01% and incidence of 0.61 per 100 patient-years. The incidence of hemorrhagic stroke was highest among patients aged 20 to 29 years [ 26 ].
In our study, the unadjusted OR for oral contraceptive use was 0.26 95% CI 0.08–0.87 with a p value of 0.028. This observation at the unadjusted level is significant but could be due to another variable which is a confounder to OC use such as higher socioeconomic status and better control of other possible risk factors.
In our study, we found no association between hypertension and stroke in young adults though it’s an independent risk factor for stroke in the older population. This finding is different from the multinational interstroke study which attributed most strokes among young adults in low- and middle-income countries to hypertension. In that study, only one fifth of the patients were from wealthier African countries where hypertension, diabetes and hypercholesterolemia are likely to occur with higher prevalence than in Mulago hospital [ 27 ]. Other studies have also reported the role of hypertension as a risk factor for stroke in young adults, low physical activity and hypertension were the most important risk factors, accounting for 59.7% and 27.1% of all strokes, respectively among a German nationwide case–control study based on patients enrolled in the SIFAP1 study (Stroke in Young Fabry Patients) 2007 to 2010 and controls from the population-based GEDA study (German Health Update) 2009 to 2010 [ 28 ]. A study that used population-based controls for hospitalized young patients with ischemic stroke demonstrated that independent risk factors for stroke were atrial fibrillation (OR 10.43; cardiovascular disease (OR, 8.01; type 1 diabetes mellitus (OR, 6.72; type 2 diabetes mellitus (OR, 2.31, low high‐density lipoprotein cholesterol (OR, 1.81; current smoking status (OR, 1.81; hypertension (OR, 1.43, and a family history of stroke (OR, 1.37) [ 29 ].
This finding could be explained by the high prevalence of hypertension in the general peri urban Ugandan population among young adults as reported by Kayima et al. 2015. He found a prevalence of 15% (95% CI 14.2 – 19.6%) % for young adults aged 18–44 years [ 30 ].
The study was conducted at Mulago hospital which is a national referral hospital in Uganda situated in central Uganda. Mulago hospital received patients both referred patients from all over Uganda and those from its catchment area. This is generally representative of the whole Ugandan population.
Uganda has a young population and with an HIV prevalence comparable to most countries in Sub-Saharan Africa, so the findings of this study are generalizable to other Sub-Saharan African populations.
Ischemic stroke is more prevalent than hemorrhagic stroke among young adults in Mulago hospital. Independent risk factors for stroke among young adults in Mulago hospital were HIV infection, elevated waist to hip ratio and sickle cell disease. Oral contraceptive use was found to be protective of stroke among young adults in Mulago hospital. There was no significant association between stroke among young adults and hypertension, diabetes, hyperlipidemia, smoking, alcohol use and illicit use.
We acknowledge the patients of Mulago hospital who gave us consent to obtain this information.
PN– conception, design of work, acquisition, analysis, interpretation of data, drafted and substantively revised the manuscript, JN– analysis, interpretation of data, drafted and substantively revised the manuscript, MK – analysis, interpretation of data, drafted and substantively revised the manuscript, EK– design of work, acquisition, analysis, interpretation of data, drafted and substantively revised the manuscript. All authors read and approved the final manuscript.
This study was funded with funds from the MEPI-Neurology program under Makerere University. The funding project had no role in the design of the study and collection, analysis, and interpretation of data and no role in writing the manuscript.
Declarations.
Written informed consent/ assent was obtained from all participants or their parent/guardian or legal authorized representative to participate in the study. Ethical approval was obtained from Makerere University, school of medicine research and ethics committee (SOMREC) (reference number #REC REF 2015–105). All methods and procedures were carried out in accordance with relevant guidelines and regulations.
Not applicable.
The authors declare that they have no competing interests.
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BMC Cardiovascular Disorders volume 24 , Article number: 495 ( 2024 ) Cite this article
Metrics details
Stroke and thromboembolism (TE) are significant complications in patients with atrial fibrillation (AF) and heart failure (HF). The impact of ejection fraction status on these risks remains unclear. This study aims to compare the risk of stroke and TE in patients with AF and HF with preserved (HFpEF) or reduced (HFrEF) ejection fraction.
Literature search of PubMed, Embase, and Scopus databases was done for studies in adult (20 years or more) population of AF patients. Included studies had reported on the incidences of stroke and/or TE in patients with AF and associated HF with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). Cohort (prospective and retrospective), case-control studies, and studies that were based on secondary analysis of data from a trial were eligible for inclusion. Methodological quality was assessed using the Newcastle Ottawa Scale (NOS). Pooled hazard ratio (HR) with 95% confidence intervals (CI) were reported. Exploratory analysis was conducted based on the different cut-offs used to define HFrEF and HFpEF.
Twenty studies were analyzed. In the overall analysis, HFrEF in AF patients was associated with a significantly reduced risk of stroke and systemic TE (HR 0.88, 95% CI: 0.81, 0.96; n = 20, I2 = 86.6%), compared to HFpEF. However, most studies showed comparable risk of stroke among the two groups of patients except for two studies that had documented significantly reduced risk. Upon doing the sensitivity analysis by excluding these two studies, we found similar risk among the two group of subjects and with no heterogeneity (HR 1.01, 95% CI: 0.99, 1.03; n = 18, I2 = 0.0%). Exploratory analysis also showed that the risk of stroke and systemic thromboembolism was similar between those with HFpEF and HFrEF.
The findings suggest that there is no significantly different risk of stroke and systemic thromboembolism in cases of AF with associated HFpEF or HFrEF. The finding does not support integration of left ventricular ejection fraction into stroke risk assessments.
Peer Review reports
Atrial fibrillation (AF) is connected to a higher incidence of stroke and systemic thromboembolism (TE) [ 1 , 2 ]. This risk is particularly significant if accompanied by heart failure (HF) [ 3 , 4 ], which is recognized as a risk factor for stroke and systemic TE [ 5 , 6 ]. Echocardiographic parameters allow to stratify HF into two distinct categories based on left ventricular ejection fraction (LVEF): HF with preserved and reduced ejection fraction (HFpEF and HFrEF, respectively) [ 7 , 8 ]. HFrEF is characterized by impaired pumping capability of the heart, which exacerbates blood stasis, and increases the risk of thrombus formation [ 9 ]. HFpEF is defined as HF despite preserved LVEF(≥ 50%), with elevated natriuretic peptides, and impaired blood flow dynamics [ 10 ]. Given the increasing prevalence of AF and HF and their intricate relationship, it becomes imperative to understand nuanced aspects of their association with the risk of stroke and TE [ 11 ].
A prior systematic review that was published in 2015 and included seven studies, investigated cardiovascular outcomes among patients with AF and HFrEF, as opposed to HFpEF [ 12 ], and revealed that HFrEF correlated with a marked increase in all-cause mortality (Risk ratio, RR 1.24; N = 10). However, there were no differences in the rates of stroke. During the following half-decade, additional studies have been conducted on this particular aspect, but no recent comprehensive updated meta-analysis attempted to summarize most current data.
This meta-analysis aims to bridge this gap by systematically reviewing and quantitatively synthesizing the available literature to compare the risk of stroke and thromboembolism in AF patients with HFpEF or HFrEF.
Study protocol.
The protocol of the review was preregistered in PROSPERO ( https://www.crd.york.ac.uk/prospero/ ) under the registration number (CRD42024505106). The meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [ 13 ].
Electronic searched were done in PubMed, Embase, and Scopus databases to identify relevant studies, published until 31st December 2023 using a combination of key terms: (Atrial fibrillation OR atrial flutter OR tachycardia) AND (heart failure OR cardiac failure OR cardiac disease) AND (preserved ejection fraction OR reduced ejection fraction OR ejection fraction OR cardiac output) AND (complications OR thromboembolism OR stroke OR cerebrovascular accident). Manual search of reference lists and review articles was also conducted.
We understand that including “atrial flutter” as a keyword was not strictly necessary. We decided to incorporate it to broaden our search and increase the number of potential studies identified. Our goal was to ensure a comprehensive review and reduce the risk of overlooking important studies that could contribute valuable data. Additionally, while not a primary reason, some studies might include results for combined cohorts of atrial fibrillation and atrial flutter patients, and we thought that this keyword may help us identify such studies as well.
This meta-analysis included studies that involved adult populations (aged 20 years or more) diagnosed with AF and concurrent HF where ejection fraction data (preserved or reduced) was documented. We included cohort studies (both prospective and retrospective), case-control studies, and studies that were based on secondary analysis of trial records. The primary outcomes of interest were risk of stroke and systemic thromboembolism in AF patients with associated HF, with a specific focus on the stratification of outcomes by ejection fraction status (HFpEF or HFrEF). Peer-reviewed English-language articles published until 31st December 2023 were considered. We excluded studies involving paediatric patients or patients without a clear diagnosis of AF and/or HR. Review articles, editorials, letters, commentaries, and studies lacking original data, such as case reports, were also excluded. Additionally, non-peer-reviewed sources, such as conference posters, as well as studies with unclear reporting of outcomes or insufficient data were excluded.
Data deduplication was done for the studies identified through the preliminary literature search. Two study authors comprehensively screened titles and abstracts of remaining studies. Full texts of studies that met the initial criteria underwent a detailed evaluation to determine eligibility for inclusion. All discrepancies or disagreements were resolved by discussions.
The Newcastle-Ottawa Scale (NOS) was employed for the standardized quality assessment of the selected studies [ 14 ]. The assessment is made based on study groups selection, intergroup comparability, and ascertainment of outcomes, with a maximum achievable value of 9. Higher scores indicate better quality [ 14 ].
Relevant data were extracted and included study authors, publication year, study location, design, subject characteristics, duration of follow-up, type of AF in the included patients, cut-off for ejection fraction used to define HFpEF and HFrEF, sample size, and key findings. Any disagreements were resolved by discussions.
Pooled effect sizes were reported as hazard ratios (HR) with 95% confidence intervals (CI). For all the statistical comparisons, HFpEF served as the reference. Subgroup analyses were conducted according to study design, type of AF, duration of follow up and sample size. The random-effects model was employed for all analysis to account for differences in participant characteristics and methodological variations among the included studies. The Cochrane I 2 > 40% indicated significant heterogeneity [ 15 ]. Publication bias was assessed by funnel plot and Egger’s test [ 16 ]. A P < 0.05 on Egger’s test indicated presence of publication bias and this was supported by visual inspection of funnel plot. All analysis were conducted using STATA software version 15.0. We evaluated the certainty of the evidence using the standard GRADE approach and GRADE Pro software [ 17 ].
Literature search across databases identified 1714 studies. After deduplication, 1226 distinct studies remained. After subsequent evaluation of titles and abstracts, full texts of 51 relevant articles were screened, and additional 31 studies were eliminated. Finally, a total of 20 studies were included (Fig. 1 ) [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ].
Process of selecting studies for inclusion
As summarized in Table 1 , there were eight studies with a retrospective and seven studies with a prospective cohort design. Remaining five studies were based on secondary analysis of data collected as part of randomized clinical trial. Most studies were conducted in the USA ( n = 7). Three studies were conducted in the Republic of Korea and one study each in Russia, Poland, Japan, Sweden, Canada, and France. Four studies were multicenter. In almost all studies, HFpEF correlated with older age and higher proportion of female gender, compared to HFrEF patients. There were differences in the cut-off values used for defining reduced or preserved ejection fraction (EF) among the included studies. Majority of the studies defined HFrEF as EF < 50% and HFpEF as ≥ 50% ( N = 8) followed by 7 studies that defined HFrEF as EF < 40% and HFpEF as ≥ 50%. This highlights a grey zone for EF between 40 and 50% that should be addressed. Only 11 studies reported on the type of AF. Out of them, eight had predominantly patients with permanent or persistent AF, two had patients with paroxysmal AF and in one study, the equal proportion of patients had either permanent/persistent or paroxysmal AF. We also reported available data from the included studies on CHA2DS2-VASc or CHADS2 score as well as NT-ProBNP or BNP level (Table 1 ). The data suggests that those with reduced ejection fraction had comparatively lower CHA2DS2-VASc/CHADS2 score and higher NT-ProBNP/ BNP level compared to those with preserved ejection fraction.
Most studies had a follow up period of more than one year ( n = 15). The follow up period in these studies ranged from 15 months to 5 years. The included studies contributed to a total of 1,73,876 subjects. The mean NOS quality score of the studies was 7.5. There were 10 studies with a score of 8 and 10 studies with a score of 7 (Supplementary Tables 1 and 2 ). Overall, quality assessment results indicate that the included studies were of acceptable methodological quality.
HFrEF patients had lower risk of stroke and systemic thromboembolism (HR 0.88, 95% CI: 0.81, 0.96; n = 20, I2 = 86.6%) compared to AF patients with HFpEF (Fig. 2 ), with no obvious publication bias (Egger’s p-value = 0.120) (Supplementary Fig. 1 ). However, most studies showed comparable risk of stroke among HFrEF and HFpEF patients except for the publication from Uhm et al. and Chung et al. Upon doing the sensitivity analysis by excluding these two studies, we found similar risk among the two group of subjects and with no heterogeneity (HR 1.01, 95% CI: 0.99, 1.03; n = 18, I2 = 0.0%) (Egger’s p-value = 0.341) (Supplementary Fig. 2 ).
Risk of stroke and systemic thromboembolism among subjects with atrial fibrillation and associated reduced ejection fraction (HFrEF), compared to patients with preserved ejection fraction (HFpEF)
Subgroup analysis showed that the reduced risk of stroke and thromboembolism in HFrEF was only evident in prospective cohort studies (HR 0.74, 95% CI: 0.58, 0.94; n = 7, I2 = 95.4%), studies with longer follow up (> 1 year) (HR 0.86, 95% CI: 0.77, 0.95; n = 15, I2 = 90.0%) and studies with larger sample size (≥ 500) (HR 0.85, 95% CI: 0.76, 0.96; n = 17, I2 = 88.3%) (Table 2 , Supplementary Figs. 3 – 9 ). No statistically significant association could be found on analysis based on the type of AF i.e., persistent or permanent AF (HR 0.86, 95% CI: 0.69, 1.07; n = 8, I2 = 86.1%) and paroxysmal AF (HR 0.66, 95% CI: 0.25, 1.77; n = 2, I2 = 98.3%) (Table 2 , Supplementary Figs. 10 and 11 ).
However, when the two studies i.e., Uhm et al. and Chung et al., were excluded from the subgroup analysis, the risk of stroke and thromboembolism was comparable in the two group of subjects (HFrEF and HFpEF) with low to negligible heterogeneity, irrespective of the study design, duration of follow up and sample size (Supplementary Figs. 12 – 14 ). We also conducted an exploratory analysis based on the cut-off used to define reduced and preserved ejection fraction. There were three sets of studies that we identified: first, where EF ≥ 50% indicated HFpEF and EF < 40% indicated HFrEF; second, where EF ≥ 50% indicated HFpEF and EF < 50% indicated HFrEF; and third, where EF ≥ 40% indicated HFpEF and EF < 40% indicated HFrEF. The findings within each of these three strata show that the risk of stroke and systemic thromboembolism is similar between those with HFpEF and HFrEF (Supplementary Fig. 15 ). The overall quality of evidence was judged to be “Low” according to the GRADE assessment criteria (Supplementary Fig. 16 ).
Our overall analysis shows that AF patients with HFrEF may have a lower risk of stroke and systemic thromboembolism than AF patients with HFpEF. However, substantial heterogeneity could affect this interpretation. The sensitivity analysis, after excluding the studies by Uhm et al. and Chung et al., clearly showed a similar risk of stroke and systemic thromboembolism between the two groups, with low heterogeneity. Subgroup analyses, after excluding these two studies, showed comparable risks of stroke and thromboembolism in the HFrEF and HFpEF groups, regardless of study design, duration of follow-up, and sample size. Our findings are consistent with and support those of a previous review that included data from seven studies ( n = 33,773 subjects) and found a comparable risk of stroke in the HFrEF and HFpEF groups [ 12 ].
If we examine the overall findings, the significantly reduced risk of stroke and thromboembolism observed in those with HFrEF, might be attributed to distinct aspects of the underlying pathophysiology. We may speculate that left ventricular (LV) diastolic dysfunction, as seen in HFpEF, contributes to a higher risk, compared to LV systolic dysfunction found in HFrEF [ 38 , 39 ]. Left atrium (LA) to left ventricle (LV) blood flow is delayed in patients with LV diastolic dysfunction, leading to blood stasis in the LA, and subsequent increase in the risk of thromboembolism and stroke [ 40 ]. However, this reason may not be sufficient, as HFrEF is also associated with some degree of diastolic dysfunction [ 41 ]. Previous study reported higher rates of hypertension and high warfarin usage rate in patients with HFpEF, which might also partly contribute to the risk [ 42 ]. Another possible explanation could be the increased age of patients and a higher proportion of female patients with HFpEF in the included studies. The “congestive heart failure, hypertension, age, diabetes mellitus, prior stroke or transient ischemic attack or thromboembolism, vascular disease, age, sex category” (CHA 2 DS 2 -VASc) score serves as a valuable tool for assessing the risk of stroke associated with AF [ 43 ]. It incorporates various clinical risk factors, including age (higher points for older age) and sex (female sex contributing to a higher score). Patients with HFpEF, therefore, may have increased CHA2DS2-VASc score, and, subsequently, higher risk of stroke and thromboembolism. This brings an interesting perspective: there may actually be no significant difference in the risk of stroke and systemic thromboembolism between the two groups. The adjusting covariates differed between the studies included in this meta-analysis. Patients with AF and HFpEF were older and had a higher prevalence of comorbidities, which, if properly adjusted for in the analysis, could have led to a comparable risk. Additionally, there were differences in the definitions of HFrEF and HFpEF among the included studies. Considering these limitations, the reduced risk of stroke in HFrEF patients might not be significant and could be overstated. The sensitivity analysis (after exclusion of Uhm et al. and Chung et al.) also supports the view that there may be no significant risk difference between the two groups. The low quality of evidence, as judged by the GRADE assessment, strongly supports the need for more studies with robust methodology to provide conclusive evidence.
There were some limitations of our review. We found significant heterogeneity in the reported outcomes which could be due to some differences in the definitions of HFpEF and HFrEF, baseline characteristics of the patients, as well as differences in the methodology (study design and follow up period). The included studies were observational in design and therefore, despite efforts to control for confounding variables, there remains a possibility that some of the important confounders may not have been accounted for. This will ultimately influence the robustness of observed associations. The often-limited longitudinal data in many of the included studies may impact the ability to capture the dynamic nature of HF and AF progression. Additionally, the impact of changing treatment modalities over time on the risk of stroke was not assessed in this review. We were also not able to provide mechanistic insights into the risk of stroke.
In conclusion, the “low” quality evidence from this meta-analysis does not provide convincing evidence that there is significantly different risk of stroke and systemic thromboembolism in cases of AF with associated HFpEF or HFrEF. The finding does not support integration of left ventricular ejection fraction into stroke risk assessments.
Nursing staff may potentially play a crucial role in preventing risk of stroke and systemic thromboembolism in patients with HF and AF. They could be instrumental in educating patients about the importance of adherence to anticoagulation therapy and regularly monitoring their health. Nursing professionals could be involved in assessing medication effectiveness, managing potential complications, and collaborating with healthcare teams for necessary treatment adjustments. They can also contribute to risk stratification, developing individualized care plans based on patient characteristics, and ensuring effective communication within multidisciplinary care teams. Considering limitations of our study, further research would need to focus on the underlying mechanisms contributing to the thromboembolic risk.
The datasets used and analysed during the current study are available from the corresponding author on reasonable request.
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Zhang, M., Zhou, J. Systematic review and meta-analysis of stroke and thromboembolism risk in atrial fibrillation with preserved vs. reduced ejection fraction heart failure. BMC Cardiovasc Disord 24 , 495 (2024). https://doi.org/10.1186/s12872-024-04133-1
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A new study from case western reserve university and university of cincinnati shows promise that a new drug may help repair damage caused by strokes. .
Currently, there are no U.S. Federal Drug Administration-approved drugs to repair the damage caused by a stroke.
But a new preclinical study by researchers at Case Western Reserve University and the University of Cincinnati (in the journal Cell Reports ) found a drug called NVG-291-R allows nervous system repair and significant functional recovery in an animal model of severe ischemic stroke.
Jerry Silver, co-author of the study and professor of neurosciences at CWRU’s School of Medicine, said the study showed the drug repaired damage through at least two avenues: creating new neuronal connections and enhancing migration of newly born neurons derived from neuronal stem cells to the site of the damage.
“NVG-291-R’s ability to enhance plasticity was demonstrated by using staining techniques that clearly showed an increase in axonal sprouting to the damaged part of the brain,” Silver said. “This enhanced plasticity is an excellent validation of the same powerful mechanisms that we and other researchers were able to demonstrate using NVG-291-R in spinal cord injury.”
Additional studies will be needed to research if NVG-291-R effectively repairs damage caused by hemorrhagic strokes in both animal models and human patients.
NervGen Pharma Corp. holds the exclusive worldwide rights to NVG-291, and the drug is being tested in a clinical trial in healthy human subjects. NervGen plans to initiate patient safety and efficacy trials in spinal cord injury, Alzheimer’s disease and multiple sclerosis in 2022 and 2023.
Agnes (Yu) Luo, associate professor in the Department of Molecular Genetics and Biochemistry in UC’s College of Medicine, was the study’s senior author.
BMC Neurology volume 24 , Article number: 345 ( 2024 ) Cite this article
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The patent foramen ovale (PFO) and interatrial block (IAB) are associated with cryptogenic stroke (CS). However, the role of the interaction between PFO and IAB in CS remains unclear.
This case–control study enrolled 256 patients with CS and 156 individuals without a history of stroke or transient ischemic attack. IAB was defined as P wave duration > 120 ms. PFO was evaluated by contrast transesophageal echocardiography, and classified as no-PFO, low-risk PFO and high-risk PFO. Multiplicative and additive interaction analysis were used to assess the interaction between PFO and IAB in CS.
Multiplicative interaction analysis unveiled a significant interaction between IAB and low-risk PFO in CS (OR for interaction = 3.653, 95% CI, 1.115–12.506; P = 0.037). Additive interaction analysis indicated that 68.4% (95% CI, 0.333–1.050; P < 0.001) of the increased risk of CS related to low-risk PFO was attributed to the interaction with IAB. The results were robust in multivariate analysis. However, but no significant multiplicative or additive interaction was observed between IAB and high-risk PFO. When stratified by IAB, high-risk PFO was associated with CS in both patients with IAB (OR, 4.186; 95% CI, 1.617–10.839; P = 0.003) and without IAB (OR, 3.476; 95% CI, 1.790–6.750; P < 0.001). However, low-risk PFO was only associated with CS in patients with IAB (OR, 2.684; 95% CI, 1.007–7.149; P = 0.048) but not in those without IAB (OR, 0.753; 95% CI, 0.343–1.651; P = 0.479).
The interaction between IAB and PFO might play an important role in CS, particularly in cases with low-risk PFO.
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Stroke is a significant contributor to global mortality and disability, of which 70% can be attributed to ischemic stroke (IS). It is essential to understand the mechanisms underlying IS for its secondary prevention. However, the etiology is undetermined in approximately 25% of IS cases, which are categorized as cryptogenic stroke (CS) [ 1 ].
Recently, the role of the patent foramen ovale (PFO) in IS has gained significant attention. PFO-related strokes account for 5% of all stroke cases and up to 10% in younger patients [ 1 ]. Randomized controlled trials have demonstrated the efficacy of PFO closure in preventing CS, reinforcing the significant role of the PFO in stroke etiology [ 1 ]. Paradoxical embolism is deemed the primary mechanism by which PFO contributes to IS [ 2 ], whereas other mechanisms, such as in situ thrombus formation [ 3 ], atrial arrhythmias, and reduced left atrial function, may also play a role in PFO-associated stroke [ 4 ]. In addition to PFO, interatrial block (IAB) is supposedly associated with IS [ 5 ]. IAB not only correlates with atrial fibrillation (AF) [ 5 ], but also increases the risk of IS in patients without AF, potentially due to left atrial blood stasis induced by IAB [ 5 , 6 ].
However, limited studies have focused on the relationship between the PFO and IAB and the role of their interactions on IS risk. The present study aimed to investigate the association between PFO and IAB and elucidate the impact of the interaction between PFO and IAB on CS risk.
This case–control study was conducted in compliance with the ethical standards of the corresponding institution and the Declaration of Helsinki. The ethics review boards of Shaoxing People’s Hospital approved this study, and the requirement for informed consent was waived owing to the retrospective nature of this study. The analysis was reported in accordance with the STROBE guidelines.
For the cryptogenic stroke group (CS group), we consecutively enrolled patients with CS aged between 18 and 75 years, who underwent contrast transesophageal echocardiography (cTEE) at the Shaoxing People's Hospital from January 2021 to December 2023. The diagnosis of CS was adjudicated by cardiologists and neurologists based on previously published criteria [ 7 ]. All stroke cases were confirmed by brain magnetic resonance imaging and neurologic examination. The following tests were performed in all patients: transthoracic echocardiography and TEE; extracranial artery ultrasound or computed tomography angiography; laboratory tests; 12-lead electrocardiography; and 24-h Holter electrocardiographic monitoring. Patients with incomplete evaluations were not considered to have CS.
The control group comprised consecutive patients without a history of stroke/ transient ischemic attack (TIA) who underwent cTEE at the Shaoxing People's Hospital during the same period.
The exclusion criteria were as follows: 1) atrial fibrillation/flutter or sustained atrial tachycardia(> 30 s); 2) atrial premature beats within a 24-h period exceeding 10,000; 3) without electrocardiography results within 1 year before IS or cTEE;4) valvular heart disease, congenital heart disease other than PFO, or cardiomyopathy; 5) heart failure stages C to D [ 8 ]; 6) left atrial anteroposterior diameter greater than 45 mm; 7) a history of stroke or TIA; 8) systemic inflammatory diseases, coagulation dysfunction or malignancies; 9) PFO-related diseases other than IS, such as migraines and decompression sickness; and 10) missing key information or other conditions deemed unsuitable for inclusion by investigators.
The last patients' ECGs within 1 year before IS or cTEE were obtained electronically. P-wave durations were measured using the MUSE v9 Cardiology Information System (GE HealthCare, UK). IAB was defined as a prolonged P-wave duration (≥ 120 ms) in the inferior leads [ 6 ]. The ECGs were analyzed by an independent experienced electrocardiologist blinded to the patients’ information.
All c-TEE examinations were performed according to local clinical protocols published previously [ 9 ]. A Philips EPIQ 7C real-time three-dimensional color cardiac ultrasound system (Philips Ultrasound, Bothell, Washington, United States) equipped with a transesophageal three-dimensional matrix probe X8-2t (frequency, 2–8 MHz) was utilized for the examinations. The contrast agent used was an agitated saline solution, administered via the antecubital vein. Images of each chamber section were observed both at rest and after a Valsalva maneuver, capturing at least 20 cardiac cycles. PFO was confirmed when the channel was visibly open and microbubbles traversed from the right to the left atrium within three cardiac cycles subsequent to right atrium opacification. All images were stored in a database and assessed by an experienced sonographer blinded to. the patients’ information.
The following characteristics of PFO were evaluated: the grading of right-to-left shunt flow (RLS), PFO size, atrial septal aneurysm (ASA) and hypermobile septum. All characteristics were evaluated at rest, except for RLS, which was evaluated both at rest and after the Valsalva maneuver.
The PFO with a right-to-left shunt (PFO-RLS) typically manifests within the initial 3–6 cardiac cycles following right atrium opacification. PFO-RLS was graded as follows: grade 0, the absence of microbubbles; grade 1, the presence of 1–10 microbubbles; grade 2, the presence of 11–30 microbubbles; and grade 3, the occurrence of > 30 microbubbles or near-complete opacification of the left atrium. The PFO height was measured as the maximum separation between the septum primum and septum secundum in the end-systolic frame, and a large-size PFO was defined as a PFO with a height exceeding 2 mm. ASA was characterized by > 10 mm septal excursion from the midline into the right or left atrium, or > 15 mm total excursion between both atria. Additionally, a moving and floppy septum, defined as > 5 mm septal excursion in every heartbeat, was categorized as a hypermobile interatrial septum [ 10 ].
The PFO with at least one of the following characteristics was defined as a high-risk PFO: PFO-RLS grade > 2 at rest or after the Valsalva maneuver, a large-size PFO, ASA or a hypermobile septum. Otherwise, the PFO was defined as low-risk PFO [ 4 , 7 ].
The patients’ medical history was retrieved from medical records. To avoid the impact of IS on laboratory test results, the laboratory tests performed after the acute stage (1–2 weeks) of IS were abstracted for analysis. In the control group, the laboratory tests were conducted within 1 week before or after the cTEE procedure.
The Kolmogorov–Smirnov test was utilized to evaluate the normal distribution of continuous variables. Normally distributed data are presented as mean ± standard deviation and were compared using the Student’s t-test. Skewed data are expressed as median (lower quartile-upper quartile) and were compared using the Mann–Whitney test. Categorical variables are presented as counts and were compared using the Fisher’s exact test or Pearson’s chi-squared test, as appropriate.
The association between CS and potential risk factors was estimated by odds ratios (ORs) with 95% confidence intervals (CIs) calculated by logistic regression. Multiplicative and additive methods were used to investigate the role of interaction between IAB and PFO in CS development. Multiplicative interaction was assessed by introducing an interaction term into the logistic regression models. Additive methods were used to calculate the following parameters: 1) the attributable proportion (AP); 2) the relative excess risk due to interaction (RERI); and 3) the synergy index (SI) [ 11 ]. Moreover, subgroup analyses were conducted to evaluate the roles of IAB and PFO in CS development.
All data analyses were performed using R version 4.2.0. The “InteractionR” package was utilized for conducting interaction analyses. Statistical significance was determined at a 2-sided p -value ≤ 0.05.
During the study, 304 patients with CS and 329 individuals without stroke/TIA underwent cTEE and ECG. We excluded 221 participants based on the exclusion criteria. Finally, 412 participants were included in the analysis. Figure 1 illustrates the participant selection process. Of the participants, 256 had CS (CS group) and the remaining 156 were classified as the control group. Participants in the CS group were older (56.7 ± 9.7 vs. 53.7 ± 13.0 years, P = 0.014) and predominantly comprised men (68.0% vs. 54.5%, P = 0.006), drinker (37.5% vs. 25.0%, P = 0.009) and smokers (29.7% vs. 20.5%, P = 0.040). Moreover, the incidences of hypertension (60.5% vs. 35.9%, P < 0.001) and diabetes (21.1% vs. 7.7%, P < 0.001) were significantly higher in the CS group. Additionally, patients in the CS group exhibited lower high-density lipoprotein (HDL) levels, larger left atrial dimensions, longer P-wave durations, and a higher IAB incidence. Regarding PFO, high-risk PFO incidence was higher in the CS group (34.8% vs. 13.5%, P < 0.001), whereas there was no significant difference in low-risk PFO incidence between the groups (14.8% vs. 15.4%, P = 0.849). Among patients with PFO, the PFO size was larger in the CS group (2.59 ± 1.37 vs. 1.99 ± 0.85 mm, P = 0.001), while the RLS grade and incidence of ASA and hypermobile septa were comparable between the groups. Table 1 summarizes the characteristics of the participants. Table 2 presents the morphometric and functional characteristics of the PFO.
Patients’ selection process. AF, atrial fibrillation; AFL, atrial flutter; AT, atrial tachycardia; cTEE, contrast transesophageal echocardiography; PAC, premature atrial complex; TIA, transit ischemic attack
In the univariate analysis, conventional risk factors, such as age, sex, alcohol, smoking, hypertension, diabetes, D-dimer levels, high density lipoprotein levels and left atrial size, showed associations with CS. In addition, IAB (OR, 1.961; 95% CI, 1.293–2.973; P = 0.002) and high-risk PFO (OR, 3.647; 95% CI, 2.127–6.251; P < 0.001) were also associated with CS, whereas low-risk PFO (OR, 1.362; 95% CI, 0.770–2.410; P = 0.288) displayed no association. Regarding to PFO characteristics, PFO size was the only factor associated with CS. Tables S1-2 show the results of the univariate analysis. After adjustment for potential confounders, the association between IAB, high-risk PFO, and CS remained significant (Table 3 ).
Before evaluating the interaction, the relationship between PFO and IAB was investigated. The incidence of IAB was comparable among participants with low-risk PFO, high-risk PFO, and those without PFO (31/62 vs. 45/110 vs. 97/240, P = 0.381). Among participants with PFO, no association was detected between IAB and PFO characteristics (Table S3).
Multiplicative interaction analysis unveiled a significant interaction between IAB and low-risk PFO (OR for interaction = 3.653, 95% CI, 1.115–12.506; P = 0.037), while no significant multiplicative interaction was observed between IAB and high-risk PFO (OR for interaction = 1.204, 95% CI, 0.378–3.841; P = 0.753). Regarding additive interaction analysis, a significant AP of 0.684 (95%CI, 0.333–1.050; P < 0.001) was observed for IAB and low-risk PFO upon using no-IAB/no-PFO as the comparator. Correspondingly, the RERI ( P = 0.073) and SI ( P = 0.079) tended to be significant. However, no significant AP, RERI and SI were detected for IAB and high-risk PFO (Table 4 ). The results of the interaction analysis remained robust after adjusting for potential confounders, as depicted in Table 4 . In the subgroup analysis, IAB conferred an increased risk of CS in patients with low-risk PFO (OR, 5.769; 95% CI, 1.843–18.064; P = 0.003) and tended to increase CS risk in patients without PFO (OR, 1.619; 95% CI, 0.960–2.732; P = 0.071). However, no significant association between IAB and CS was detected in patients with high-risk PFO (OR, 1.950; 95% CI, 0.693–5.491; P = 0.206). When stratified by IAB, high-risk PFO was associated with CS in both patients with IAB (OR, 4.186; 95% CI, 1.617–10.839; P = 0.003) and without IAB (OR, 3.476; 95% CI, 1.790–6.750; P < 0.001). However, low-risk PFO was only associated with CS in patients with IAB (OR, 2.684; 95% CI, 1.007–7.149; P = 0.048) but not in those without IAB (OR, 0.753; 95% CI, 0.343–1.651; P = 0.479).
The present study found a significant interaction between IAB and low-risk PFO pertaining to CS risk. The results of the multiplicative interaction analysis and subgroup analysis indicated that isolated low-risk PFO was not associated with CS; however, when combined with IAB, low-risk PFO increased the risk of CS. The additive interaction results suggested that nearly 70% of the increased risk of CS associated with low-risk PFO was attributed to the interaction with IAB. Nevertheless, no significant multiplicative interaction between high-risk PFO and IAB was observed. Correspondingly, IAB was significantly associated with CS in patients with low-risk PFO, but not in those with high-risk PFO and without PFO.
PFO has been considered as an important risk factor for CS [ 1 ]. The prevalence of PFO is approximately 25% in the general population. Not all PFOs lead to stroke. Identifying high-risk PFOs is a crucial aspect of secondary prevention for patients with CS and may even serve as an important strategy for primary prevention. Currently, the diagnosis of PFO-associated strokes is primarily determined by clinical characteristics and the high-risk features of the PFO. In addition to clinical characteristics and the features of the PFO, the present study suggested that IAB was a neglected but important factor modifying the risk of PFO in CS and should be considered in clinical practice. There are several potential mechanisms underlying the interactions between PFO and IAB.
First, IAB may increase PFO-RLS, thereby raising the risk of paradoxical embolism associated with PFO. Although the mechanisms behind PFO-associated strokes are not fully understood, paradoxical embolism is considered a major contributing factor. PFO-RLS forms the basis of paradoxical embolism and stands as the most significant risk factor for PFO-associated strokes [ 1 ]. Factors leading to an increase in PFO-RLS, such as ASA, prominent Chiari network, and Eustachian valve, may increase CS risk [ 10 ]. Previously, researchers have focused primarily on the morphological factors of PFO that may lead to an increase in PFO-RLS. However, the impact of abnormal atrial electrical activity on PFO-RLS remains unclear. Normal atrial electrical activity originates from the sinoatrial node, and travels through the Bachmann bundle, interatrial septum, and coronary sinus to activate the left atrium. Therefore, the right atrium contracts earlier than the left atrium. When the right atrium contracts before the left, its pressure exceeds that of the left atrium, leading to PFO-RLS. Therefore, when IAB further delays the contraction of the left atrium, the risk of paradoxical embolism increases. A previous study reported that atrial mechanical dyssynchrony, a consequence of IAB, increased PFO-RLS [ 12 ]. Second, PFO may exacerbate the left atrial blood stasis caused by IAB. IAB itself is a risk factor for CS. The mechanisms underlying CS caused by IAB may be associated with left atrial blood stasis [ 5 ]. PFO-RLS may exert a significant effect on left atrial hemodynamics. A recent study reported that PFO-RLS may reduce stroke in the patients with AF by increasing left atrial appendage emptying velocity [ 13 ]. However, in a computational fluid dynamics study, PFO-RLS contributed to increased blood stasis in the left atrium [ 14 ]. Third, IAB may be associated with the risk of in situ thrombus formation in PFO. In addition to the paradoxical embolism, the PFO may also lead to in situ thrombus formation [ 3 ]. IAB may be associated with increased interatrial septal fat, a local marker of endothelial dysfunction and myocardial fibrosis [ 15 , 16 ]. Therefore, IAB may be associated with the risk of in situ thrombus formation in PFO.Furthermore, IAB may also be associated with other risk factors of PFO-associated stroke, such as a hypermobile septum and left atrial enlargement [ 17 , 18 ]. Overall, in theory, a complex interaction may exist between the IAB and PFO in the causation of CS. Future studies are warranted to explore the potential mechanisms underlying the interaction between PFO and IAB.
In the present case–control study, we demonstrated a significant interaction between IAB and PFO in the development of CS. Similar to previous studies, the present study did not observe a significant association between low-risk PFO and CS [ 1 ]. However, low-risk PFO increased the risk of CS approximately thrice in patients with IAB. This finding holds crucial clinical significance. Currently, the diagnosis of PFO-associated stroke is primarily based on clinical features and PFO morphology. In patients with low-risk PFO, the probability of PFO-associated stroke is usually considered low. However, based on our findings, we should not neglect the significance of low-risk PFO in patients with IAB. With regard to high-risk PFO, similar to previous studies, we confirmed the significant association between high-risk PFO and CS. However, it was interesting that no significant interaction between IAB and high-risk PFO was detected. It was speculated that the strong association between high-risk PFO and CS might overshadow the role of interaction between high-risk PFO and IAB negligible. For example, the large RLS of high-risk RLS would dilute the impact of IAB on PFO-RLS, as mentioned above. To further explore the mechanism underlying the interaction between IAB and PFO, we assessed the correlation between IAB and the high-risk features of PFO, including PFO-RLS, ASA, and hypermobile septum, but no significant association was detected. While we did not demonstrate that IAB increases the PFO-RLS, it may still extend the duration of PFO-RLS. Whether this may increase the probability of paradoxical embolism requires further investigation. Furthermore, these results suggest that the interaction between IAB and PFO may be independent of PFO-RLS.
This study had several limitations. First, as a single-center study, the findings should be interpreted with caution and require further validation through multi-center studies. Second, the retrospective design introduces significant bias, particularly selection bias, since the study included only patients who underwent cTEE at our center, potentially resulting in a higher incidence of PFO compared to the general population. However, due to the low incidence of CS, conducting a prospective cohort study would be challenging. Despite these limitations, the primary aim of this study was to investigate the interaction between PFO and IAB. We demonstrated that IAB is not associated with PFO or its characteristics, minimizing the impact of selection bias on the assessment of the interaction. Additionally, subgroup analyses further validated the interaction between PFO and IAB. Lastly, we did not provide evidence for the mechanism underlying PFO and IAB interaction, thus warranting further investigation.
In summary, our study highlights the significant interaction between interatrial block (IAB) and patent foramen ovale (PFO) in cryptogenic strokes, mainly in those with low-risk PFO. These findings enhance our understanding of the mechanisms underlying CS and provide valuable insights into preventive measures.
The datasets analysed during the current study are available from the corresponding author on reasonable request.
Atrial fibrillation
Attributable proportion
Atrial septal aneurysm
Contrast transesophageal echocardiography
Confidence intervals
Cryptogenic stroke
Interatrial block
Ischemic stroke
Patent foramen ovale
Right-to-left shunt flow
Relative excess risk due to interaction
Synergy index
Transient ischemic attack
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This work was supported by the Health Commission of Zhejiang Province, China (grant number: 2024KY481), and the Health Commission of Shaoxing, China (grant number: 2022KY031).
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Department of Neurology, Shaoxing People’s Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing, 312000, China
Ye Du & Yanxing Zhang
Department of Cardiology, Shaoxing People’s Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), 568 # Zhongxing North Road, Shaoxing, Zhejiang Province, 312000, China
Yangbo Xing & Buyun Xu
Department of Ultrasound, Shaoxing People’s Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing, 312000, China
Xiatian Liu
Department of Electrocardiogram, Shaoxing People’s Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing, 312000, China
Huayong Jin
Zhejiang University School of Medicine, Hangzhou, 310000, China
Yuxin Zhang
Shaoxing University School of Medicine, Shaoxing, 312000, China
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Conception and design: Ye Du, Buyun Xu, Yanxing Zhang, Yangbo Xing; administrative support: Buyun Xu; provision of study materials or patients: Ye Du, Yanxing Zhang, Yangbo Xing, Xiatian Liu, Huayong Jin; collection and assembly of data: Ye Du, Yanxing Zhang, Yuxin Zhang, Chengyi Li; data analysis and interpretation: Ye Du, Buyun Xu; manuscript writing: all authors; and final approval of the manuscript: all authors.
Correspondence to Buyun Xu .
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The ethics review boards of Shaoxing People’s Hospital approved this study, and the requirement for informed consent was waived owing to the retrospective nature of this study.
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Du, Y., Zhang, Y., Xing, Y. et al. Role of interatrial block in modulating cryptogenic stroke risk in patients with patent foramen ovale: a retrospective study. BMC Neurol 24 , 345 (2024). https://doi.org/10.1186/s12883-024-03829-3
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It is challenging to simultaneously conduct total endovascular repair and reconstruct the left subclavian artery (LSA) and isolated left vertebral artery (ILVA) in patients who had an ILVA and required zone 2 anchoring. This pilot study reported the initial application experience of thoracic endovascular aortic repair (TEVAR) with a proximal zone 2 landing for aortic arch reconstruction in patients with ILVA.
This study was a retrospective consecutive single-center case series analysis, which involved four patients with ILVA who required zone 2 anchoring and received TEVAR combined with a single-branched stent graft and concomitant on-table fenestration between March 2021 and December 2022.
The postoperative follow-up period was 6–27 months, and no postoperative deaths or other primary complications occurred. There were no signs of a stroke or spinal cord ischemia, as well as no chest or back pain. The postoperative computed tomography angiography showed unobstructed ILVA and LSA, no stent stenosis and displacement, and no signs of endoleak.
The outcome suggested that this technique might be a feasible, safe, and alternative treatment for such patients. Further studies with larger samples and longer follow-up periods are needed to confirm our findings.
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The isolated left vertebral artery (ILVA) originates from the aortic arch and is usually located between the left common carotid artery (LCCA) and the left subclavian artery (LSA). It is the second most common congenital anomaly of the aortic arch with an incidence of 1.7 to 4.3% [ 1 ]. It is often required to cover LSA and ILVA and establish an adequate proximal landing zone when this aberration is found during thoracic endovascular aortic repair (TEVAR) of aortic arch pathologies. Open revascularization techniques like carotid-subclavian bypass are commonly employed for the treatment of patients with LSA coverage, especially for non-ILVA cases. Improper management of ILVA may result in brain ischemia or infarction [ 2 ]. However, due to the limited data obtained from case reports, the optimal treatment for aortic arch diseases combined with ILVA remains unclear. This study reported the treatment effect of TEVAR in patients with ILVA who underwent zone 2 anchoring with a single-branched stent graft and concomitant on-table fenestration.
It was a retrospective single-center case series study. All patients with aortic arch pathologies who underwent TEVAR between March 2021 and December 2022 were retrospectively evaluated ( n = 159). Patients without ILVA ( n = 152), patients with ILVA and who received on-table single big fenestration ( n = 1), and those following ILVA translocation and LCCA-LSA bypass ( n = 1) were excluded from the analysis. Finally, patients following on-table fenestration with the branched stent graft comprised the study cohort ( n = 4; Fig. 1 ). The Institutional Ethics Committee approved the study (IRB number, 2023-RE-123). Participants were not required to provide informed consent due to the retrospective nature of this study. All patients underwent preoperative computed tomography angiography (CTA) of the aortic arteries. Endosize software (Therenva SAS, Rennes, France) was used to evaluate vertebral artery dominance, ILVA diameter, aortic arch type and pathology, the distance between ILVA and LSA, location of the primary entry tear, maximum aortic diameter, and true or false lumen. The aortic reconstruction was completed with CTA in a central-line protocol mode.
Flow diagram for the enrollment of patients treated by TEVAR with a proximal zone 2 landing Note TEVAR, thoracic endovascular aortic repair; ILVA, isolated left vertebral artery
This study used the Castor stent (MicroPort Endovascular, Shanghai, China) as a novel unibody single-branched stent with on-table fenestration for endovascular repair of the aortic arch (Fig. 2 ). Acute type B aortic dissection (AD) patients were treated with medications to control their blood pressure and heart rate. Surgery was performed at least one week after the onset of acute AD when the clinical condition was stable. All procedures were performed in a conventional supine position under general anesthesia and were given 1.5 g of intravenous cefuroxime sodium 30 min before surgery to prevent surgical infection. The systemic heparin was administered at 100 IU/kg after the percutaneous arterial puncture. The stent was 5 to 10% oversized the maximum diameter of the true lumen in zone 2 (Fig. 3 ). The proximal part of the Castor stent was released out of its outer sheath at the operating table. An on-table fenestration was made to preserve the ILVA. The location and size of the fenestration were determined based on the preoperative aortic CTA measurement. The coating part of the stent was excised with a surgical blade for on-table fenestration (Fig. 4 ). The Castor stent was inserted into the delivery system and should avoid being distorted and shortened.
Schematic diagram of surgery. Castor stent as a novel unibody single-branched stent with on-table fenestration for endovascular repair of the aortic arch. Note BT, brachiocephalic trunk; LCCA, left common carotid artery; LSA, left subclavian artery; ILVA, isolated left vertebral artery; TL, true lumen; FL, false lumen
ILVA originating from the aortic arch by preoperative CTA. (A) Transverse plane; (B) Coronal plane; (C) 3D reconstruction model. Note BT, brachiocephalic trunk; LCCA, left common carotid artery; LSA, left subclavian artery; ILVA, isolated left vertebral artery; TL, true lumen; FL, false lumen
On-table fenestration of the Castor stent graft. A Castor branched stent graft; B The outer sheath was released; C The proximal part of the Castor stent was released out of its soft sheath; C An on-table fenestration was made to preserve the ILVA. Note ILVA, isolated left vertebral artery
The detailed operation of the Castor stent was described earlier [ 3 ]. The right femoral artery (RFA) was exposed through a right inguinal incision. The left femoral artery (LFA) and left brachial artery (LBA) were punctured to insert the 6 F sheath. A contrast catheter was inserted into the ascending aorta through the RFA. The diagnosis was confirmed by angiography and preoperative imaging data. The access at LBA and RFA was established to ensure the successful insertion of the catheter in the true lumen of the aorta. A 0.035-inch super-stiff guidewire (Amplatz, Olympus, USA) was inserted into the ascending aorta via the RFA. The main body of the Castor stent was introduced through the super stiff guidewire, and its branch section was introduced into LSA through the access at LBA and RFA. A contrast catheter was placed into the ascending aorta through the sheath in the LFA to confirm that the proximal end of the main body of the Castor stent was located at the posterior edge of the LCCA ostium and that the branch section was pulled into the LSA. The medication treatment was used to maintain the patient’s systolic blood pressure at around 90 mmHg for the deployment of the main body. The main body and the branch section were released successively (Fig. 5 ). The angiography catheter was sent to the ascending aorta again. After the angiography confirmed a satisfactory position of the stent, the delivery system, guide wires, and catheters were withdrawn, and the puncture sheath was removed. The incisions at RFA and right groin were sutured. Hemostasis was achieved by pressing the LFA and LBA puncture sites. After surgery, the patients was treated with 100 mg of aspirin once a day for one year. The aortic CTA was performed six, 12, and 24 months postoperatively. All patients underwent physical examination one month after surgery and were followed up until June 2023.
Successful reconstruction of LSA and LVA confirmed by intraoperative angiography and postoperative CTA. A Intraoperative angiography demonstrated type B aortic dissection and the origin of ILVA from the aortic arch between LCCA and LSA before stent-graft insertion; B Intraoperative angiography revealed that the branch section of the Castor stent was pulled into the LSA; C Intraoperative angiography revealed complete coverage of the primary tear of the aortic dissection without endoleak and normal flow of ILVA and LSA after the Castor stent release; D 3D-CTA showed the patency of ILVA and LSA and the favorable revascularization of aorta arch without endoleak at the three-month follow-up. Note LCCA, left common carotid artery; LSA, left subclavian artery; ILVA, isolated left vertebral artery; TL, true lumen; FL, false lumen; 3D-CTA, 3-dimensional computed tomographic angiography
Between March 2021 and December 2022, four patients in our center, including three cases of acute aortic dissection and one of aortic aneurysm, underwent ILVA and LSA reconstruction using a single-branched stent graft with the on-table fenestration technique. Their preoperative data are shown in Table 1 . The mean age of the patients was 62.8 ± 15.3 years (range, 48–76 years). The total time for creating the on-table fenestration (unsheathing and re-sheathing of the thoracic endograft) was about 20 to 30 min. The mean operation time was 118 ± 21.3 min (range, 91–141 min). The technical success rate (defined as ILVA patency) was 100%. The mean postoperative length of hospital stay was 9.8 ± 5.7 days (range, 3–14 days). Intraoperative angiography confirmed complete isolation of the primary entry tear and ILVA and LSA patency. The postoperative follow-up period was 6–27 months, with an average of 15.8 ± 9.9 months. No postoperative deaths or other primary complications occurred. Besides, there were no stroke or spinal cord ischemia symptoms and no further chest and back pain. One postoperative patient refused to undergo CTA due to renal insufficiency. The postoperative CTA of other patients showed patent ILVA and LSA, false lumen thrombosis, no stent stenosis or displacement, and no signs of endoleak (Fig. 4 ).
It is difficult to reconstruct LSA and ILVA while performing TEVAR in patients with ILVA requiring zone 2 anchoring. Normal vertebral arteries can form the basilar arteries and supply blood to the cerebellum and brainstem. The prevalence of a complete Willis circle is 42% in the Western population and 27% in Chinese people [ 4 , 5 ]. ILVA is not associated with any clinical symptoms; however, it may increase the risk of spinal cord injury (SCI) and cerebral infarction after aortic arch surgery. It remains controversial to cover ILVA during TEVAR, and there are no clear guidelines and few relevant reports. If there exists insufficient vascular connection at the Willis circle, covering ILVA may reduce the brain stem or cerebellar perfusion and increase the risk of neurological deficits. Emerging evidence has suggested that a potential reduction in the brain stem or cerebellar perfusion due to VA occlusion could contribute to nerve injury [ 6 , 7 ].
Previous studies have compared the early and late outcomes of conventional open surgery and hybrid surgery (ILVA translocation and LCCA-LSA bypass) for aortic lesions with ILVA and concluded a favorable effect in both methods [ 8 , 9 ]. Nevertheless, elderly or high-risk patients might not tolerate median sternotomy and its fatal complications. In contrast, hybrid surgery was less invasive than open surgery and showed mild to moderate complications, including bleeding from the wound, wound infection, bypass obstruction, and local nerve damage. Therefore, total endovascular repair during this procedure might reduce the risk of brain disease, early mortality, and length of hospital stay. Recent guidelines suggested that LSA revascularization should be performed during zone 2 TEVAR with an insufficient anchoring zone in non-emergency patients [ 10 ]. The branched stent technique was superior to other methods for LSA reconstruction because it did not cause type Ia (common in chimney technique) and III leakage (common in fenestration technique). The incidence of stent restenosis was high due to the small diameter of ILVA. Therefore, ILVA endograft should be avoided as much as possible. The simultaneous reconstruction of LSA and ILVA using single or double on-table fenestration was a feasible technique for the endovascular repair of ILVA. The cerebral ischemia might occur during traditional on-table fenestration of arch lesions due to misalignment of the fenestration. One prior study found that two patients with dizziness had a partial misalignment of the fenestration to the origin of the ILVA and insufficient blood perfusion of the cerebellum [ 11 ]. We successfully applied a novel “Castor” single branched-stent graft with on-table fenestration to optimize the process of endovascular ILVA reconstruction and reduce the risk of cerebral ischemia. In addition to the successful reconstruction of the blood flow of LSA, the anchoring and positioning effects of the branch section could help quickly and accurately determine the fenestration site and avoid the possibility of poor alignment during fenestration. All ILVA patients were confirmed to have accurate alignment by the results of immediate imaging after stent implantation and postoperative CTA, and there were no postoperative brain complications.
The study had certain limitations. This was a single-center, retrospective observational study with limited samples and relatively shorter follow-up periods. In addition, this study lacked a control group.
In summary, our study with limited samples suggested that the unibody single-branched stent graft combined with on-table fenestration was a safe, feasible therapeutic for patients with ILVA who required zone 2 anchoring. Nevertheless, our finding needed to be confirmed by further studies with larger samples and longer follow-up times.
All generated or analyzed data, as well as the materials used during this study were included in this article.
Left Subclavian Artery
Isolated Left Vertebral Artery
Thoracic Endovascular Aortic Repair
Left Common Carotid Artery
Computed Tomography Angiography
Aortic Dissection (AD)
Right Femoral Artery
Left Femoral Artery
Left Brachial Artery
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We acknowledged all the contributions by the participating doctors from our department.
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Department of Cardiovascular Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China (USTC), Hefei, China
Xiang Kong, Jiquan Yu, Peng Ruan & Jianjun Ge
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Xiang Kong designed the work and wrote the main manuscript. Jiquan Yu, and Peng Ruan collected and analyzed the patients’ data. Xiang Kong and Jianjun Ge revised the final manuscript. All authors read and approved the final manuscript.
Correspondence to Xiang Kong .
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The present study was approved by the institutional review board of The First Affiliated Hospital of University of Science and Technology of China (USTC), Division of Life Sciences and Medicine, USTC. (IRB number, 2023-RE-123). Participants were not required to provide informed consent due to the retrospective nature of this study.
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Kong, X., Yu, J., Ruan, P. et al. Single-branched stent-graft with on-table fenestration for the management of zone 2 landing TEVAR with an isolated left vertebral artery: a pilot study. J Cardiothorac Surg 19 , 528 (2024). https://doi.org/10.1186/s13019-024-03024-y
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DOI : https://doi.org/10.1186/s13019-024-03024-y
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CASE 1. A 20 year old man with no past medical history presented to a primary stroke center with sudden left sided weakness and imbalance followed by decreased level of consciousness. Head CT showed no hemorrhage, no acute ischemic changes, and a hyper-dense basilar artery. CT angiography showed a mid-basilar occlusion.
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Patient Case Presentation. Image courtesy of uofmhealthblogs.org. D.B. is a 72 year old African American female who presented to the ED with complaints of headache, altered mental status as evidenced by confusion and lethargy, slurred speech, right sided weakness, and a facial droop. Symptoms were first noted when patient woke up from a nap ...
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We compared 961 patients with a first‐ever IS at 25 to 49 years to 1403 frequency‐matched stroke‐free controls from a population‐based cohort study (FINRISK).Assessed risk factors included an active malignancy, atrial fibrillation, cardiovascular disease, current smoking status, a family history of stroke, high low‐density lipoprotein cholesterol, high triglycerides, low high ...
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A 66-year-old man was admitted to hospital with a right frontal cerebral infarct producing left-sided weakness and a deterioration in his speech pattern. The cerebral infarct was confirmed with CT imaging. The only evidence of respiratory symptoms on admission was a 2 L oxygen requirement, maintaining oxygen saturations between 88% and 92%. In a matter of hours this patient developed a greater ...
In Uganda, literature on stroke in young adults is limited however results of a study done among acute stroke patients admitted to the national referral hospital (Mulago hospital) showed a 30-day mortality of 43.8%. Out of 133 patients, 32 patients (25%) were less than 51 years old. Out of the 56 patients that died, 13 patients (23%) were less ...
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It was a retrospective single-center case series study. All patients with aortic arch pathologies who underwent TEVAR between March 2021 and December 2022 were retrospectively evaluated (n = 159).Patients without ILVA (n = 152), patients with ILVA and who received on-table single big fenestration (n = 1), and those following ILVA translocation and LCCA-LSA bypass (n = 1) were excluded from the ...