1 Introduction

Total hip arthroplasty (THA) is the second most common joint arthroplasty surgery in the United States (US), with over 250,000 surgeries performed each year.¹ With the growing aging population, this number is expected to surpass one million surgeries per year by 2050.¹ As THAs become more common, it is imperative that risk factors associated with adverse perioperative outcomes are better understood. As with all surgical interventions, THA may have numerous risks including previous literature reported stroke, pulmonary embolism (PE), and deep vein thrombosis (DVT) as among the most morbid complications^2–6.

Patent foramen ovales (PFOs) and atrial septal defects (ASDs) are both congenital cardiac abnormalities that result in open access between the left and right atria.⁷ Individuals with PFOs and ASDs are at an increased risk for stroke, as the opening between the right and left atria creates a path by which emboli can migrate from the venous system to arterial system, potentially leading to paradoxical stroke.⁷ ASDs and PFOs are not uncommon and present in approximately 1.6 per 1000 live births and 25% of adults, respectively.^8,9 Compared to patients without ASDs, individuals with ASDs experience a greater lifetime risk of perioperative stroke and morbidity.¹⁰ This investigation categorizes ASDs and PFOs as inter-atrial wall abnormalities (IAWAs).

This study sought to investigate the relationship between IAWAs and same-admission postoperative adverse outcomes including procedure-related complications, and mortality following THA, with a focus on thromboembolic complications which included ischemic stroke, PE, and DVT. We hypothesize that patients with IAWAs have higher risks of complications following THA when compared to patients without.

2 Materials and methods

We performed a retrospective cohort study utilizing the Healthcare Cost and Utilization Project (HCUP) National Inpatient Sample (NIS) database from 2010-2021.¹¹ Cases were identified using the International Classification of Disease-9 (ICD-9) procedure code for THA (81.51) between January 2010 to August 2015 and the ICD-10 procedure code for THA (0SR9019, 0SR901A, 0SR901Z, 0SR9029, 0SR902A, 0SR902Z, 0SR9039, 0SR903A, 0SR903Z, 0SR9049, 0SR904A, 0SR904Z, 0SR9069, 0SR906A, 0SR906Z, 0SR90J9, 0SR90JA, 0SR90JZ, 0SRB019, 0SRB01A, 0SRB01Z, 0SRB029, 0SRB02A, 0SRB02Z, 0SRB039, 0SRB03A, 0SRB03Z, 0SRB049, 0SRB04A, 0SRB04Z, 0SRB069, 0SRB06A, 0SRB06Z, 0SRB0J9, 0SRB0JA, 0SRB0JZ) between September 2015 and December 2021.

Furthermore, patients with ICD-9-CM diagnosis code 7455 or ICD-10-CM diagnosis code Q211 were assigned to the cohort of patients with a prior history of IAWAs. The study excluded patients <18 years old or those with concurrent congenital heart defects (CHDs), trisomy 21, or hypercoagulability disorders. Cases with missing data were also excluded for complete case analysis.

Propensity score matching (PSM) was performed at a ratio of one patient with an IAWA to twenty patients without an IAWA. The propensity score algorithm matched patients based on age group, gender, insurance status, history of smoking, history of osteoporosis, history of inflammatory arthritis, history of atrial fibrillation, Charlson Comorbidity Index (CCI), hip fracture, hospital size, hospital location/teaching status, and hospital ownership.

Comorbidities were classified according to the Charlson coding schematic described by Quan et al.¹² Primary outcomes included same-admission procedure-related complications and same-admission mortality. Procedure-related complications included those specified by the Technical Expert Panel from the Centers for Medicare & Medicaid Services (CMS): acute myocardial infarction, pneumonia or other respiratory complication, sepsis/septicemia/shock, surgical site bleeding or other surgical site complication, thromboembolic complications, mechanical complication, and periprosthetic joint infection (PJI)/wound infection or other wound complication.¹³ Thromboembolic complications consisted of ischemic stroke, PE or DVT.

All analyses were performed using R Statistical Software (v4.4.2; R Core Team; 2024). Univariate cohort differences were identified using chi-square test or Fisher's exact tests. PSM adjusted logistic regression was utilized for the evaluation of associations between exposure and outcome variables. Measures of association were presented as odds ratio (OR) with 95% confidence interval (CI). Statistical significance was defined at an alpha level of p < 0.05. This study was Institutional Review Board (IRB) exempt as the data contains de-identified, publicly accessible information.

3 Results

Our study identified 816,624 cases involving THA that fulfilled study inclusion criteria, among which 780 (0.096%) and 815,844 (99.90%) involved patients with and without IAWA, respectively. Both cohorts had the higher proportions of patients who were women, had White race/ethnicity, no history of smoking, Medicare insurance, CCI of 0, had no history of inflammatory arthritis, had no history of osteoporosis, had no fracture, and had no history of atrial fibrillation. Also, both cohorts had the highest proportion of patients who underwent THA at large, urban teaching and private, not-for-profit hospitals [Table 1].

After a 1:20 propensity score matching, we identified 780 (4.76%) patients in the IAWA cohort and 15,600 (95.24%) patients in the non-IAWA cohort. Matching balanced all preoperative demographic characteristics between the IAWA and non-IAWA cohorts. Thus, the matched cohorts have no significant differences in age group, gender, race/ethnicity, history of smoking, insurance status, Charlson Comorbidity Index (CCI) score, history of inflammatory arthritis, history of osteoporosis, hip fracture, history of atrial fibrillation, nor hospital characteristics [Table 2].

4 Discussion

Our study investigated the relationship between IAWAs and same-admission outcomes following THA and found that patients with IAWAs had higher odds of procedure-related complications but not mortality. In the subgroup analysis of procedure-related complications, patients with IAWAs also had higher risks for thromboembolic complications -- which included ischemic stroke, PE, and DVT.

Understanding the risk factors for thromboembolic complications is critical as their physical, cognitive and social impacts may cause major deteriorations in patient quality of life. In 2019, stroke was the third leading cause of death and disability, globally, behind neonatal disorders and ischemic heart disease.¹⁴ Other thromboembolic complications such as PE also have deleterious long-term effects on quality of life.¹⁵ Thromboembolic complications are also a major contributor to health care costs. The national cost of direct stroke-related medical care is projected to reach $184.13 billion by 2030.¹⁶ Beyond the initial stroke treatment, patients also incur significant lifetime costs associated with rehab and long-term ambulatory care.¹⁷ DVT and PE also cause significant economic burden, with some studies estimating a median total cost of over $25,000.¹⁸ In the context of increasing emphasis on health care outcomes and simultaneous rising health care costs, understanding risk factors for thromboembolic events is a top priority for clinicians.

This study builds on previous literature on the association between IAWA and thromboembolic complications. Our findings were consistent with those by Perfetti et al. who used NIS data from 2007 to 2013 and found an increased risk of stroke in patients with IAWAs following THA.¹⁹ However, this study did not account for important confounding factors such insurance status, baseline hospital characteristics and history of atrial fibrillation -- a major risk factor for stroke. It also did not examine outcomes such as PE, DVT, and mortality. Our study found similar associations as a study by Chughtai et al., who reported an increased odds of stroke among patients with IAWAs following TJA.²⁰ However, their study did not account for smoking or atrial fibrillation as potential confounders. They also did not examine outcomes beyond stroke.

A study by Magruder et al. found increased risks for cerebrovascular accident (including stroke), DVT and PE in the IAWA versus the non-IAWA cohort.²¹ Our analysis found similar results and additionally matched patients based on potential confounders including baseline demographics and health status through the use of the CCI. In a similar study investigating TKA, patients with IAWAs were also found to be have an increased risk of perioperative stroke, PE, and DVT.⁶ Our results were inconsistent with a study by Bido et al. who reported zero embolic events within 90 days following TJA.²² Their cohort contained a small sample size of 160 patients with IAWAs and less than 100 THAs were included in the study. Taken together, the results of our study are largely consistent with the existing literature regarding IAWA's and postoperative outcomes after TJA. This study contributes to the existing literature by utilizing robust statistical analysis and over a decade of data to investigate the connection between IAWAs and multiple key outcomes including ischemic stroke, PE and DVT in the context of THA.

A major strength of our study is its generalizability, as it involved a large nationwide sample of patients. We also excluded patients with hypercoagulability disorders, CHDs and aneuploidy, as these conditions may have inherent susceptibility to poor surgical outcomes or are often associated with IAWAs.

This study has several limitations. As with all large database studies, the reported information is subject to clerical errors and coding inconsistencies. The NIS also does not have data on patient BMI nor anticoagulation use.

Despite these limitations, the NIS is a large national database that is intended to provide information on patient and hospital characteristics as well as short-term surgical outcomes. Therefore, the findings of this study are likely generalizable. Further studies examining the role of stroke and thrombotic prophylaxis may help improve surgical outcomes in patients with IAWAs who undergo THA.

5 Conclusion

Compared to patients without IAWAs, those with IAWAs who underwent THA had higher risks for same-admission procedure-related complication but not same-admission mortality. Within the procedure-related subgroup analysis, patients with IAWAs had higher risks of ischemic stroke, PE and DVT. Further research is needed to optimize perioperative THA management and decrease the risk of thromboembolic complications.

Ethical consent

This study was Institutional Review Board (IRB) exempt as the data contains de-identified, publicly accessible information.

Patient consent

Informed consent for patient information to be published in this article was not obtained because the data set used contains all de-identified, publicly available data.

Author contributions

Bruce B Zhang: Wrote the original draft of the manuscript, formal data analysis, investigation.

Abdullah A Uddin: Formal data analysis, validation.

David H Mai: Data curation, methodology, project administration, supervision.

Joshua Buksbaum: Significant review and editing.

Margaret Lee: Significant review and editing.

Qais Naziri: Conceptualization, data curation, project administration, resources, supervision.

All authors reviewed the manuscript.

Funding statement

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.