Skip to main content
Download PDF
  • Systematic Review
  • Open access
  • Published:

Risk of stroke in patients with congenital heart disease: a systematic review and meta-analysis

BMC Neurology volume 24, Article number: 465 (2024) Cite this article

Abstract

Background

Patients with congenital heart disease (CHD) are more likely to experience ischemic and hemorrhagic stroke due to factors such as arrhythmias, residual shunts and related cardiovascular complications. However, guidelines for identifying CHD patients at the highest risk of stroke remain unclear. In this study, we aimed to evaluate the risk of developing stroke in patients with CHD.

Methods

A systematic literature search was performed on PubMed, Scopus, Cochrane, and Embase databases to retrieve studies that evaluated stroke risk in patients with CHD. Random effects model was used to pool the hazard ratios (HR) with 95% confidence intervals (CI). Subgroup analysis was conducted on age, type of stroke, type of study and region. Publication bias was assessed by Egger’s regression test. Statistical significance was set at p < 0.05. All the analysis was performed using R studio V4.3.1.

Results

Eleven studies (5,490,412 participants) were included in this systematic review and meta-analysis. Patients with CHD were at a higher risk of stroke [Pooled HR: 3.25; 95% CI: 2.25, 4.68; p < 0.01; I2: 100%] than the control group. In subgroup analysis, patients with CHD were at a higher risk of ischemic stroke [Pooled HR: 4.45; 95% CI: 2.24, 8.85; p < 0.01; I2: 100%] and hemorrhagic stroke [Pooled HR: 4.70; 95% CI: 1.70, 12.96; p < 0.01; I2: 99%] than the control group.

Conclusion

Our meta-analysis indicates a significantly increased stroke risk in patients with CHD. Subgroup analyses showed higher stroke risk in European regions compared to Asia and USA, and among adults compared to pediatric populations. Future studies should focus on addressing regional and data limitations to better inform clinical strategies for managing stroke risk in CHD patients.

Graphical Abstract

Peer Review reports

Introduction

Stroke is one of the leading causes of impairments and global health issues [1]. Heart diseases, particularly heart failure, are significant contributors to the development of stroke [2]. The impaired cardiac function in heart failure often leads to reduced cerebral perfusion, arrhythmias, and the formation of blood clots, all of which increase the risk of ischemic stroke [2]. Congenital heart disease (CHD) is the most prevalent congenital disorder affecting approximately 1% of live births globally [3]. CHD includes mild to severe conditions, with a global prevalence varying due to healthcare access, diagnostic technologies, and genetic or environmental factors. Asia has the highest prevalence at 9.3 per 1,000 live births, followed by North America and Europe at 8.1 and 8.2 per 1,000 live births, respectively [4]. CHD significantly contributes to infant morbidity and mortality, with delayed diagnosis being critical in lower-income regions, such as Latin America and parts of Asia [5].

Survival rates for individuals born with CHD have significantly improved, with approximately 97% of children now reaching adulthood [6]. Advances in surgery, cardiology, and healthcare have shifted the prevalence towards adulthood. In the 1950s, only 15% of children with CHD survived to adulthood; today, over 90% survive, including individuals in their 60s [7]. Despite these advancements, adults with CHD have a 3.2-fold higher mortality risk than the general population [8]. The increasing adult CHD population presents challenges, such as managing comorbidities, complex interventions, and lifelong care needs.

Adults with congenital heart disease (ACHD) are at increased risk for multiple comorbidities, including heart failure, coronary artery disease, mental health challenges, and other chronic conditions that exacerbate their overall health outcomes [9, 10]. Patients with CHD have a higher risk of stroke owing to heart failure, arrhythmias, and defect complexity. Atrial fibrillation (AF) significantly increases this risk, with CHD patients having a five-fold higher probability of ischemic stroke than non-CHD patients with AF. Those with Tetralogy of Fallot and other complex anomalies are especially prone to atrial arrhythmias, increasing the likelihood of thromboembolic events, including stroke and transient ischemic attack [11, 12].

New-onset arrhythmias, particularly when accompanied by heart failure, aggravate the stroke risk by increasing hemodynamic instability and encouraging thromboembolism. Previous studies highlighted an elevated risk of stroke in young adults aged 20–29, especially in those with multiple atherosclerotic risk factors [13, 14]. Stroke risk in CHD patients is estimated to be 10–100 times greater than that in the general population. Furthermore, a case–control study conducted in Taiwan demonstrated a 2.2 times higher likelihood of stroke in adults with five common types of CHD compared to healthy controls [15, 16].

Stroke outcomes frequently result in significant neurological impairment and require substantial rehabilitation. This study investigated the existing evidence on stroke risk among CHD patients, identifying specific risk patterns within CHD subgroups and pinpointing areas needing further research to enhance care and patient outcomes.

Materials and methods

This systematic review and meta-analysis were made and reported in line with the guidelines of Preferred Reporting Items for Systematic Review and Meta-Analysis Statement (PRISMA 2020) [17,18,19].

Search strategy

A systematic search was conducted in several databases including Medline (via PubMed), Embase, the Cochrane Library, Scopus, was conducted from their inception to August 2024, using a combination of keywords related to the stroke and congenital heart disease: (“stroke” OR “Cerebrovascular Accident” OR “Vascular Accident” OR “CVA” OR “ischemic stroke” OR “transient ischemic attack” OR “TIA” OR “hemorrhagic stroke”) AND (“congenital heart disease” OR “congenital heart defects” OR “CHD” OR “Heart Abnormality” OR “Heart Defect” OR “Malformation Of Heart”). The search strategy was adjusted according to the demands of specific databases.

Study selection and eligibility criteria

To determine the studies to be included in this review, the following inclusion criteria were used: (i) studies assessing the risk of stroke development in heart defects and (ii) randomized controlled trials or observational studies. Studies were included regardless of patient age, sex, race, socioeconomic background, and geographical location. Inaccessible full texts, abstracts, review articles, letters to editors, case reports, and case series were excluded. Two examiners (H.B. and R.M.) independently screened introductory studies based on their titles and abstracts. A third examiner (A.A.) was consulted for cases of disparity.

Data extraction and quality assessment

Data from acceptable studies, such as the first author, publication year, country, number of patients, risk factors, and clinical outcomes, were extracted into a tested Excel spreadsheet by two independent examiners (A.A. and R.M.). To ensure integrity and remove errors, the two examiners cross-checked and verified the extraction sheet. The Newcastle-Ottawa Scale (NOS) for cohort studies was used to assess the quality of the included studies [20]. A study with a total score between 10 and 15 is considered ‘good quality’; a score between 6 and 9 is deemed ‘fair quality,’ whereas a score between 0 and 5 is indicative of a ‘poor quality.’ Two examiners (H.B. and A.B.) completed the quality assessment, and a third examiner (S.A.) was consulted in cases of contradiction in judgment.

Data analysis

Statistical analysis was conducted using R Studio [21]. The pooled hazard ratio (HR) with a 95% cnfidence interval was calculated using the DerSimonian-Laird random effects model. The pooled HR for outcomes was estimated using a multivariable model, with factors modified for age, sex, comorbidities, smoking status, and socioeconomic status. Statistical significance was determined if the 95% cnfidence interval for the pooled HR did not cross the neutral value “1” and the two-tailed p-value was less than 0.05. The Higgins I2 metric was used to evaluate statistical heterogeneity, with 25–50% cnsidered mild, 50–75% idicating moderate heterogeneity, and > 75% svere heterogeneity [22]. Sensitivity analysis was conducted to evaluate the effect of each study on the overall effect assessment by the “leave-one-out method” [23, 24]. Subgroup analysis was performed based on country, study type, and patient age to assess their influence on the overall effect. Publication bias was assessed using funnel plot visualization and Egger’s regression test [24]. A p-value of > 0.05 for publication bias assessment indicated insignificant publication bias.

Results

Search results

Our search strategy yielded 301 studies from PubMed, Scopus, Cochrane, and Embase. After eliminating duplicates, 155 studies were screened by title and abstract, leading to the exclusion of 144. The remaining 11 full-text articles were assessed by the same authors, and 11 [25,26,27,28,29,30,31,32,33,34,35]were deemed eligible for inclusion (Fig. 1).

Fig. 1
figure 1

Flow chart of the selection process

Full size image

Characteristics of included studies

A total of 5,490,412 participants were included in the analysis, with 491,930 in the CHD group and 4,998,482 in the control group. The publication years spanned from 2008 to 2023. Two studies were conducted in Asia [32, 35], two in the United States [26, 31], seven in Europe [25, 27,28,29,30, 33, 34]. The baseline characteristics of all the studies included in this meta-analysis are illustrated in (Table 1).

Table 1 Characteristics of the included studies. * median & IQR
Full size table

Outcomes

The risk of stroke was reported in all eleven studies. Patients with CHD were at a higher risk of stroke [Pooled HR: 3.25; 95% CI: 2.25, 4.68; p < 0.01; I2: 100%] than the control group (Fig. 2). A leave-one-out analysis was performed to address the high heterogeneity. However, excluding any single study did not result in significant changes in the direction of the overall effect (Figure S1). Publication bias was insignificant on Egger’s regression test (P = 0.333) with no concern for funnel plot asymmetry (Figure S2). A subgroup analysis was conducted to determine the influence of region, study type, age. The combined risk of stroke among patients with CHD was found to be significantly elevated in various regions: in Europe, the pooled hazard ratio (HR) was 4.81 (95% confidence interval [CI]: 3.30 to 4.68; p < 0.01; I²: 95%); in Asia, the pooled HR was 1.90 (95% CI: 1.67 to 2.16; p < 0.01; I²: 96%); and in the USA, the pooled HR was 1.52 (95% CI: 0.88 to 2.63; p < 0.01; I²: 99%) (Figure S3a).

Fig. 2
figure 2

Meta analysis of the risk of stroke (ischemic and hemorrhagic) in patients with CHD

Full size image

In the subgroup analysis based on study type, the pooled risk of stroke among patients with CHD varied significantly: in prospective studies, the pooled HR was 5.33 (95% confidence interval [CI]: 1.32 to 21.43; p < 0.01; I²: 98%); in retrospective studies, the pooled HR was 2.79 (95% CI: 1.71 to 4.55; p < 0.01; I²: 98%); and in case-control studies, the pooled HR was 3.63 (95% CI: 1.91 to 6.90; p < 0.01; I²: 98%) (Figure S3b). In the subgroup analysis according to age, the pooled risk of stroke among patients with CHD revealed significant findings: for adults only, the pooled HR was 3.27 (95% confidence interval [CI]: 2.31 to 4.62; p < 0.01; I²: 100%); whereas for studies including both adults and children, the pooled HR was 5.28 (95% CI: 1.31 to 21.22; p < 0.01; I²: 99%) (Figure S3c).

According to type of stroke, four studies assessed the risk of ischemic stroke among patients with CHD. Patients with CHD were at a higher risk of ischemic stroke [Pooled HR: 4.45; 95% CI: 2.24, 8.85; p < 0.01; I2: 100%] than the control group (Fig. 3). A subgroup analysis was conducted to determine the influence of region, study type, age. The pooled risk of ischemic stroke among patients with CHD in Europe was 5.85 (95% CI: 3.21 to 10.67; p < 0.01; I²: 96%) (Figure S4a).

Fig. 3
figure 3

Subgroup analysis of by the type of stroke

Full size image

In retrospective studies, the pooled risk of ischemic stroke among patients with CHD was 2.72 (95% CI: 1.42 to 5.20; p < 0.01; I²: 99%) (Figure S4b). For adults only, the pooled risk of ischemic stroke among patients with CHD was 3.34 (95% CI: 1.93 to 5.78; p < 0.01; I²: 100%) (Figure S4c).

Only two studies assessed the risk of hemorrhagic stroke among patients with CHD [25, 35]. Lee et al., 2023 [35]defined the hemorrhagic stroke as intracerebral, subarachnoid, and subdural hemorrhagic stroke. However, Giang et al., 2018 [25]assessed the risk of intracerebral hemorrhagic stroke and subarachnoid hemorrhagic stroke separately. Patients with CHD were at a higher risk of hemorrhagic stroke [Pooled HR: 4.70; 95% CI: 1.70, 1296; p < 0.01; I2: 99%] than the cotrol group (Fig. 3).

Quality assessment

We performed a quality assessment for nine cohorts and two case-control studies. Following the NOS Study Quality Assessment Tool guidelines, eight studies were considered of high quality and one of moderate quality. For case control studies, one was considered of high quality, and one was low quality (Table S1).

Discussion

Rising mortality and morbidity due to neurovascular decline in patients with CHD has garnered attention. However, statistical evidence supporting a definitive protocol is limited [36]. Given CHD’s complexity of CHD, addressing research gaps necessitates statistical analysis of existing data, which this meta-analysis aimed to validate. Our findings show a significantly increased stroke risk in patients with CHD, with ischemic strokes being more common than hemorrhagic strokes. Subgroup analysis indicated a higher occurrence in adults than in the combined adult and pediatric groups, and a greater prevalence in Europe than in Asia.

Among neurological manifestations, we observed a heightened stroke risk in the CHD population. A recent Danish study (1977–2018) reported stroke risk in 18.9% of males and 11.4% of females with CHD, particularly in those with atrial septal defects (ASD) [37]. Contrary to Danish findings, Bokma et al. identified CHD type (simple or severe) as a predictor of stroke rather than thromboembolic phenomena [38]. Our current analysis indicates a 4.5-fold increase in ischemic stroke risk, consistent with Pedersen et al. [28]. However, Holmgren et al. attributed the risk primarily to atrial fibrillation, excluding shunt or valvular issues, resulting in a relatively lower HR in their depiction. Fox et al. further emphasized the issue, finding a 19-fold increase in stroke risk among CHD patients, corroborating our results [39].

Escalated stroke risk affiliated with dysrhythmias in CHD was anomalous disarray in the conduction system and anatomical variation offering competitive challenges for its dissolution. Not limited to this, turbulent blood flow in dilated heart chambers provokes pro-coagulants prevailing thromboembolism which is postulated to be a root cause for anoxic brain injury with an ultimate stroke presentation [40]. With hyperviscosity cascade valvular endothelium under stress of congenital malformation accumulates the predisposition for infective endocarditis followed by slow but progressive cerebrovascular changes ending with a stroke of newer onset [41, 42]. The alternating shorter recovery period with successive stroke events may offset the qualitative life, raising mortalities among such patients. Volume pressure variations based on the congenital evolution of cardiac structures may impose compensatory mechanisms in the vascular territory of the brain enhancing the stroke risk as well [31]. Despite an aggressive pre-amptive anti-coagulation scheme, co-existing mechanistic links secondary to paradoxical embolism heighten stroke events claiming to be of anatomical origin. Persistent shunts, coarctation of the aorta, and various surgical or medical interventions introduced at the earliest to apprehend morbidity were forecasted to mount hemorrhagic stroke among CHD patients [25]. Several mechanisms and risk factors associated with developing stroke in patients with CHD.

An Australian cohort study indicated that ischemic stroke (2.3%) is more common than hemorrhagic stroke (0.4%) in young adults, supporting our findings on the incidence of hemorrhagic stroke [43]. Our analysis suggested a higher risk of ischemic stroke in the young CHD population. Shunts and left-sided lesions are associated with an increased stroke incidence in CHD patients compared to those without CHD [38]. CHD patients exhibit a younger age of ischemic stroke onset, with a risk factor of 3.8 as per Pedersen et al. [28], rising by 1.6 times with age (> 60 years), which is consistent with Pedersen et al. [28]. The risk of ischemic stroke increases with age and is less pronounced in older than in younger patients. Lanz et al. reported a 9- to 12-fold higher risk in patients under 55, with a smaller increase of 2 to 4 times for those aged 55–64 [44]. Additional studies showed a tenfold risk increase in younger age groups [29] and a 16-fold increase in findings by Giang et al., supporting our pooled analysis [27]. While the higher risk at younger ages aligns with our data, Lanz et al.‘s results lack cohort comparison, and Mandalenakis et al. focused on children and young adults.

Our results indicate that CHD-associated hemorrhagic stroke was statistically significant but occurred less frequently than ischemic stroke. Observational studies, such as those by Lanz et al., reported a hemorrhagic stroke incidence of only 14 per 100,000 person-years [44], while another study documented 1.18 per 10,000 person-years [25]. Swedish data have identified non-conotruncal defects and coarctation of the aorta as primary lesions for ICH and SAH, respectively [25]. Unlike IS, which occurs in young adults, hemorrhagic stroke was observed in children with ICH and SAH at ages 4 and 1 year, respectively [43].

In our study, adults showed a higher incidence than the combined incidence in adults and children. Advances in cardiac intervention have improved childhood survivability but have increased the risk of thromboembolic events [45]. Surgical interventions during childhood often lead to perioperative thromboembolic phenomena, with some strokes occurring early and others occurring after 5 years of age [46, 47]. This may explain our findings that heart failure, cardiomegaly, and hypertension become more pronounced in adulthood. A recent study also reported a 46% higher stroke incidence in adults, attributed to previous surgical interventions, especially shunt procedures (OR 4.20; 95% CI 1.36–12.9) and mechanical valve issues (OR 2.67; 95% CI 1.09–6.50) [38]. Previous studies also support a low absolute but high relative risk of stroke with advancing age [48].

Despite being statistically significant, European regions were hypothesized to have a higher stroke risk than Asia and USA as revealed by our subgroup analysis. The higher incidence of cerebrovascular accidents, up to 0.05% annually, in Europe could explain the increased stroke risk among patients with CHD [49]. Lifestyle, genetics, early diagnosis, economic status, and racial differences across regions may also contribute to stroke risk [50]. The inclusion of nearly six studies from Europe in our analysis may have skewed the results.

The limitations of our study must be acknowledged to pave the way for innovative future strategies; about 50% of the data in our analysis come from Europe, raising concerns about the generalizability of our findings. Also, the included studies did not specify the types of CHD in the patient populations, making it unfeasible to perform a subgroup analysis based on CHD type. Additionally, studies using inpatient registers without documenting variables such as blood pressure or medications may affect the assessment of individual stroke-related risk [25]. Misdiagnosis, variable classification, or coding issues in register-based data can distort the results, raising concerns about its application. Survivorship bias due to insufficient follow-up data, as noted by Giang et al., is another limitation [25, 27].

Conclusion

In conclusion, this meta-analysis demonstrates a significantly elevated risk of stroke in patients with CHD compared to controls. The findings indicate that stroke risk varies regionally, with higher rates observed in Europe than in Asia and USA and highlights the need for targeted monitoring and management strategies in this vulnerable population. Further research is warranted to explore specific CHD types and their associated stroke risks, addressing limitations noted in existing studies.

Data availability

Data is provided within the manuscript or supplementary information files.

Abbreviations

CHD:

Congenital heart disease

HR:

Hazard ratios

CI:

Confidence intervals

ACHD:

Adults with congenital heart disease

AF:

Atrial fibrillation

NOS:

Newcastle-Ottawa Scale

ASD:

Atrial septal defects

ICH:

Intracerebral hemorrhage

SAH:

Subarachnoid hemorrhage

References

  1. Guzik A, Bushnell C. Stroke epidemiology and risk factor management. CONTINUUM: Lifelong Learn Neurol. 2017;23(1):15–39.

    Google Scholar 

  2. Ravandi F, Haj Mohamad Ebrahim Ketabforoush A, Azedi F, Hoshyarkhani M, Fayyaz F, Abbasi Khoshsirat N. Heart failure status among Acute ischemic stroke patients: a hospital-based study. Neurol Res Int. 2022;2022:1–6.

    Article  Google Scholar 

  3. Ashiq S, Ashiq K. Genetic perspective of the congenital heart disease. Pakistan Heart J. 2020;53(3).

  4. Liu Y, Chen S, Zühlke L, Black GC, Choy MK, Li N et al. Global birth prevalence of congenital heart defects 1970–2017: updated systematic review and meta-analysis of 260 studies. Int J Epidemiol. 2019;48(2).

  5. Araujo JJ, Araujo JJ. Adults with congenital heart disease in the Americas - where we are today and where we are heading: a General View of the inter-american adult congenital heart Disease Council. J Integr Cardiol Open Access. 2020;1–5.

  6. Dellborg M, Giang KW, Eriksson P, Liden H, Fedchenko M, Ahnfelt A et al. Adults with congenital heart disease: Trends in Event-Free Survival Past Middle Age. Circulation. 2023;147(12).

  7. Brida M, Gatzoulis MA. Adult congenital heart disease: Past, present and future. Vol. 108, Acta Paediatrica, International Journal of Paediatrics. 2019.

  8. Lotto R, Thomet C. Emerging adulthood: The ageing problem of congenital heart disease. Vol. 27, Nursing in Critical Care. 2022.

  9. Portal D, Hirsch R, Benderly M. Increased prevalence of cardiac and non-cardiac chronic morbidity among adults with congenital heart disease. Int J Cardiol Congenital Heart Disease. 2022;7.

  10. Cocomello L, Taylor K, Caputo M, Cornish RP, Lawlor DA. Health and Well-being in surviving congenital Heart Disease patients: an Umbrella Review with synthesis of best evidence. In: Frontiers in Cardiovascular Medicine. Vol 9. Switzerland; 2022. p. 870474.

  11. Holmgren A, Dellborg M, Mandalenakis Z, Giang KW, Eriksson P, Fedchenko M. Ischemic stroke in patients with congenital heart disease and atrial fibrillation. Eur Heart J. 2022;43(Supplement_2):ehac544.1808. https://doiorg.publicaciones.saludcastillayleon.es/10.1093/eurheartj/ehac544.1808.

  12. Tsui C, Wan D, Grewal J, Kiess M, Barlow A, Human D et al. Increasing age and atrial arrhythmias are associated with increased thromboembolic events in a young cohort of adults with repaired tetralogy of Fallot. J Arrhythm. 2021;37(6).

  13. Poisson SN, Hills NK, Sidney S, Fullerton HJ. Prevalence of atherosclerotic risk factors among children and young adults with arterial ischemic stroke. JAMA Neurol. 2022;79(9).

  14. Yang H, Kuijpers JM, de Groot JR, Konings TC, van Dijk A, Sieswerda GT et al. Impact of atrial arrhythmias on outcome in adults with congenital heart disease. Int J Cardiol. 2017;248.

  15. Lin YS, Liu PH, Wu LS, Chen YM, Chang CJ, Chu PH. Major adverse cardiovascular events in adult congenital heart disease: a population-based follow-up study from Taiwan. BMC Cardiovasc Disord. 2014;14.

  16. Hoffmann A, Chockalingam P, Balint OH, Dadashev A, Dimopoulos K, Engel R et al. Cerebrovascular accidents in adult patients with congenital heart disease. Heart. 2010;96(15).

  17. Jain H, Odat RM, Goyal A, Jain J, Dey D, Ahmed M, et al. Association between psoriasis and atrial fibrillation: a systematic review and meta-analysis. Curr Probl Cardiol. 2024;49(6):102538.

    Article  PubMed  Google Scholar 

  18. Goyal A, Jain H, Maheshwari S, Jain J, Odat RM, Saeed H, et al. Association between inflammatory bowel disease and atrial fibrillation: a systematic review and meta-analysis. IJC Heart Vasculature. 2024;53:101456.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25(9):603–5.

    Article  PubMed  Google Scholar 

  21. Balduzzi S, Rücker G, Schwarzer G. How to perform a meta-analysis with R: a practical tutorial. Evid Based Mental Health. 2019;22(4):153–60.

    Article  Google Scholar 

  22. Higgins JPT. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557–60.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Nolte IM. Metasubtract: an R-package to analytically produce leave-one-out meta-analysis GWAS summary statistics. Bioinformatics. 2020;36(16):4521–2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Lin L, Chu H. Quantifying publication Bias in Meta-Analysis. Biometrics. 2018;74(3):785–94.

    Article  PubMed  Google Scholar 

  25. Giang KW, Mandalenakis Z, Dellborg M, Lappas G, Eriksson P, Hansson PO, et al. Long-term risk of hemorrhagic stroke in young patients with congenital heart disease. Stroke. 2018;49(5):1155–62.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Maxwell BG, Wong JK, Kin C, Lobato RL. Perioperative outcomes of major noncardiac surgery in adults with congenital heart disease. Anesthesiology. 2013;119(4):762–9.

    Article  PubMed  Google Scholar 

  27. Giang KW, Fedchenko M, Dellborg M, Eriksson P, Mandalenakis Z. Burden of ischemic stroke in patients with congenital heart disease: a Nationwide, Case-Control Study. J Am Heart Assoc. 2021;10(13):e020939.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Pedersen MGB, Olsen MS, Schmidt M, Johnsen SP, Learn C, Laursen HB, et al. Ischemic stroke in adults with congenital heart disease: a Population-based Cohort Study. J Am Heart Assoc. 2019;8(15):e011870.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Mandalenakis Z, Rosengren A, Lappas G, Eriksson P, Hansson PO, Dellborg M. Ischemic stroke in children and young adults with congenital heart disease. J Am Heart Assoc. 2016;5(2).

  30. Billett J, Cowie MR, Gatzoulis MA, Vonder Muhll IF, Majeed A. Comorbidity, healthcare utilisation and process of care measures in patients with congenital heart disease in the UK: cross-sectional, population-based study with case-control analysis. Heart. 2008;94(9):1194–9.

    Article  CAS  PubMed  Google Scholar 

  31. Yelton SEG, Flores S, Sun LR, Nelson-McMillan K, Loomba RS. Association between Congenital Heart Disease and stroke: insights from a National Database. Pediatr Cardiol. 2024;45(1):1–7.

    Article  PubMed  Google Scholar 

  32. Lin YS, Liu PH, Wu LS, Chen YM, Chang CJ, Chu PH. Major adverse cardiovascular events in adult congenital heart disease: a population-based follow-up study from Taiwan. BMC Cardiovasc Disord. 2014;14:38.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Dellborg M, Björk A, Pirouzi Fard MN, Ambring A, Eriksson P, Svensson AM, et al. High mortality and morbidity among adults with congenital heart disease and type 2 diabetes. Scand Cardiovasc J. 2015;49(6):344–50.

    CAS  PubMed  Google Scholar 

  34. Videbæk J, Laursen HB, Olsen M, Høfsten DE, Johnsen SP. Long-Term Nationwide Follow-Up study of simple congenital heart Disease diagnosed in otherwise healthy children. Circulation. 2016;133(5):474–83.

    Article  PubMed  Google Scholar 

  35. Lee JS, Choi J, Shin HJ, Jung JM, Seo WK. Incidence and risk of stroke in Korean patients with congenital heart disease. J Stroke Cerebrovasc Dis. 2023;32(12):107408.

    Article  PubMed  Google Scholar 

  36. Parker, Devin M et al. Population-based estimates of the prevalence of children with congenital heart Disease and Associated Comorbidities in the United States. Circ Cardiovasc Qual Outcomes. 2024;17(9):e010657. https://doiorg.publicaciones.saludcastillayleon.es/10.1161/CIRCOUTCOMES.123.010657.

  37. El-Chouli M, Meddis A, Christensen DM, Gerds TA, Sehested T, Malmborg M et al. Lifetime risk of comorbidity in patients with simple congenital heart disease: a Danish nationwide study. Eur Heart J. 2023;44(9).

  38. Bokma JP, Zegstroo I, Kuijpers JM, Konings TC, Van Kimmenade RRJ, Van Melle JP et al. Factors associated with coronary artery disease and stroke in adults with congenital heart disease. Heart. 2018;104(7).

  39. Fox CK, Sidney S, Fullerton HJ. Community-based case-control study of childhood stroke risk associated with congenital heart disease. Stroke. 2015;46(2).

  40. Fox CK, Kamel H. Congenital heart Disease, Atrial Fibrillation, and ischemic stroke risk. J Am Heart Assoc. 2024;13(17).

  41. Kalezi ZE, Simbila AN, Nkya DA, Kubhoja SD, Majani NG, Furia FF. Infective endocarditis in children with heart diseases at Jakaya Kikwete Cardiac Institute, Tanzania: a cross-sectional study. BMC Pediatr. 2024;24(1):612.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Odat M, Marsool Marsool R, Nguyen MD, Idrees D, Hussein M, Ghabally AM. M, Pre- and post-surgery: advancements in artificial intelligence and machine learning models for enhancing patient management in infective endocarditis. Int J Surg (London, England). 2024;110(11):7202–14. https://doiorg.publicaciones.saludcastillayleon.es/10.1097/JS9.0000000000002003.

  43. Sodhi-Berry, Nita et al. Incidence and predictors of stroke in Australian adults with congenital heart disease (2000–2017). J Am Heart Assoc. 2024;13(17):e034057. https://doiorg.publicaciones.saludcastillayleon.es/10.1161/JAHA.123.034057.

  44. Lanz J, Brophy JM, Therrien J, Kaouache M, Guo L, Marelli AJ. Stroke in adults with congenital heart disease incidence, cumulative risk, and predictors. Circulation. 2015;132:25.

    Article  Google Scholar 

  45. Attar H, Sachdeva A, Sundararajan S. Cardioembolic stroke in adults with a history of congenital heart disease. Stroke. 2016;47(5).

  46. Bonthrone AF, Stegeman R, Feldmann M, Claessens NHP, Nijman M, Jansen NJG et al. Risk factors for Perioperative Brain lesions in infants with congenital heart disease: a European collaboration. Stroke. 2022;53(12).

  47. Ottaviani G, Buja LM. Congenital heart disease: Pathology, natural history, and interventions. In: Cardiovascular Pathology. 2022.

  48. Giannakoulas G, Ntiloudi D. Acquired cardiovascular disease in adult patients with congenital heart disease. Vol. 104, Heart. 2018.

  49. Prokšelj K. Stroke and systemic embolism in adult congenital heart disease. Int J Cardiol Congenital Heart Disease. 2023;12.

  50. Udine ML, Evans F, Burns KM, Pearson GD, Kaltman JR. Geographical variation in infant mortality due to congenital heart disease in the USA: a population-based cohort study. Lancet Child Adolesc Health. 2021;5(7).

Download references

Acknowledgements

Not applicable.

Funding

None.

Author information

Authors and Affiliations

  1. Faculty of medicine, Jordan University of Science and Technology, Irbid, Jordan

    Ramez M. Odat, Husam Aldean H. Hussain, Abdel Rahman K. Bani Yaseen & Bassel Alrabadi

  2. Lahore General Hospital Lahore, Lahore, Punjab, Pakistan

    Muhammad Idrees

  3. Department of Internal Medicine, All India Institute of Medical Sciences (AIIMS), Jodhpur, India

    Hritvik Jain

  4. King Hussein Cancer Center, Amman, Jordan

    Sakhr Alshwayyat

  5. Internship, Princess Basma Teaching Hospital, Irbid, Jordan

    Sakhr Alshwayyat

  6. Applied Science Research Center, Applied Science Private University, Amman, Jordan

    Sakhr Alshwayyat

  7. Faculty of Medicine, Ain Shams University, Cairo, Egypt

    Basma Badrawy Khalefa

  8. Faculty of Medicine, Al Yarmouk University, Irbid, Jordan

    Ali O. Aldamen

  9. School of Medicine, University of Jordan, Amman, Jordan

    Mohammad-Amer A. Tamimi

  10. Faculty of Medicine, Al- Balqa’ Applied University, Salt, Jordan

    Ayham Mohammad Hussein

  11. Faculty of Medicine, University of Kalamoon, Al-Nabk, Syria

    Hamdah Hanifa

  12. Department of Pediatrics of Saint Louis University, School of Medicine, SSM Health Cardinal Glennon Children’s Hospital, Missouri, MO, USA

    Osama Aloudat

Authors
  1. Ramez M. Odat
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Muhammad Idrees
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Hritvik Jain
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Sakhr Alshwayyat
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Husam Aldean H. Hussain
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. Basma Badrawy Khalefa
    View author publications

    You can also search for this author inPubMed Google Scholar

  7. Ali O. Aldamen
    View author publications

    You can also search for this author inPubMed Google Scholar

  8. Abdel Rahman K. Bani Yaseen
    View author publications

    You can also search for this author inPubMed Google Scholar

  9. Bassel Alrabadi
    View author publications

    You can also search for this author inPubMed Google Scholar

  10. Mohammad-Amer A. Tamimi
    View author publications

    You can also search for this author inPubMed Google Scholar

  11. Ayham Mohammad Hussein
    View author publications

    You can also search for this author inPubMed Google Scholar

  12. Hamdah Hanifa
    View author publications

    You can also search for this author inPubMed Google Scholar

  13. Osama Aloudat
    View author publications

    You can also search for this author inPubMed Google Scholar

Contributions

R.M.O.: Study concept, Design, Data extraction, Analysis, Scientific writing and Drafting of the manuscript. M.I.: Analysis, Scientific writing and Drafting of the manuscript. H.J., S.A., H.H.H., B.B.K., A.O.A., A.K.B., B.A., M.A.T., A.M.H., H.H.: Scientific writing and Drafting of the manuscript. O.A.: Supervision, Validation, Editing.

Corresponding author

Correspondence to Hamdah Hanifa.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Material 1

Supplementary Material 2

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Odat, R.M., Idrees, M., Jain, H. et al. Risk of stroke in patients with congenital heart disease: a systematic review and meta-analysis. BMC Neurol 24, 465 (2024). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12883-024-03967-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12883-024-03967-8

Keywords

BMC Neurology

ISSN: 1471-2377

Contact us