Nationwide Study Reveals Atrial Fibrillation Doubles Mortality Risk in Pulmonary Embolism Patients

By Ugo Aliogo

A multi-institutional research team has published compelling evidence that atrial fibrillation (AF) dramatically worsens outcomes for patients hospitalized with pulmonary embolism (PE), with in-hospital mortality rates more than doubling compared to PE patients without the arrhythmia. The nationwide analysis, published in American Heart Journal Plus: Cardiology Research and Practice, provides the most comprehensive examination to date of how AF affects the clinical trajectory of PE hospitalization in the United States.

The study, led by Dr. Mubarak Hassan Yusuf of St. Joseph University Medical Center’s Division of Pulmonary and Critical Care, analyzed data from 1,128,269 PE hospitalizations recorded in the National Inpatient Sample database between 2016 and 2021. The research team included collaborators from multiple institutions, with Dr. Olayiwola Akeem Bolaji of Memorial Sloan Kettering Cancer Center’s Division of Cardiology contributing data analysis expertise alongside colleagues from Lincoln Medical Center, University of Nigeria Teaching Hospital, and Federal Teaching Hospital in Katsina.

The findings reveal a stark reality: among over 1.1 million PE hospitalizations, the 12.4 percent with concurrent AF experienced mortality rates of 6.05 percent, compared to just 2.75 percent in patients without the arrhythmia. After adjusting for multiple confounding variables, including age, comorbidities, and socioeconomic factors, AF remained independently associated with a 67 percent increased odds of in-hospital death (adjusted odds ratio: 1.67; 95% CI 1.56–1.79; p<0.0001).

Beyond mortality, AF patients with PE experienced significantly higher rates of life-threatening complications. The odds of cardiac arrest were 59 percent higher (aOR: 1.59; 95% CI 1.45–1.74), cardiogenic shock was 20 percent more likely (aOR: 1.20; 95% CI 1.03–1.39), and acute respiratory failure was 12 percent more common (aOR: 1.12; 95% CI 1.09–1.16). Patients with AF were also 65 percent more likely to require invasive mechanical ventilation.

The pathophysiological relationship between AF and PE creates what the researchers describe as a dangerous synergy. Pulmonary embolism acutely elevates right atrial pressure, which can trigger or exacerbate atrial fibrillation. Conversely, AF compromises atrial contraction, promotes blood stasis, and may independently contribute to thrombus formation. When these conditions coexist, the hemodynamic consequences compound each other, overwhelming the cardiovascular system’s compensatory mechanisms.

The analysis revealed distinct demographic patterns among affected patients. Those with concurrent AF and PE were substantially older (mean age 73.6 years versus 61.6 years), more likely to be male (53.55% versus 47.57%), and carried higher comorbidity burdens. Over 45 percent of AF patients had a Charlson Comorbidity Index score of three or higher, compared to 28 percent of non-AF patients. Conditions including heart failure (41% versus 14.5%), chronic kidney disease (22% versus 12%), and chronic obstructive pulmonary disease (27% versus 16.5%) were markedly more prevalent.

The study documents substantial resource utilization differences between the two populations. Hospital length of stay averaged 5.66 days for PE patients with AF, compared to 4.18 days for those without—a difference of approximately 35 percent. Total hospital charges reflected this disparity, averaging $65,235 for AF patients versus $50,118 for non-AF patients, representing an adjusted mean difference of $9,391 per hospitalization.

These findings carry significant implications for healthcare systems facing an aging population with rising prevalence of both conditions. Atrial fibrillation affects approximately 1 to 2 percent of the adult population globally, with rates increasing substantially with age. Simultaneously, PE remains one of the leading causes of cardiovascular mortality, with over 100,000 deaths annually in the United States alone.

The research team emphasizes several actionable conclusions for clinical practice. First, the presence of AF should be recognized as a significant prognostic indicator in PE patients, warranting heightened vigilance and potentially more aggressive monitoring. Current PE severity scoring systems, including the Pulmonary Embolism Severity Index (PESI) and its simplified version (sPESI), do not incorporate AF status—a gap the authors suggest should be addressed through future risk stratification tool development and validation.
Second, the findings support routine screening for AF in patients presenting with PE. Many cases of AF remain undiagnosed until acute presentation, delaying critical interventions such as anticoagulation optimization and rhythm management. Early detection enables more comprehensive treatment planning and may improve outcomes.

Third, the study highlights the importance of multidisciplinary collaboration in managing these complex patients. The intersection of PE and AF demands expertise spanning pulmonary medicine, cardiology, and critical care. Structured protocols for early detection and coordinated management could improve outcomes while optimizing resource utilization.

The researchers employed a retrospective cohort design using the National Inpatient Sample, the largest all-payer inpatient database in the United States, representing approximately 20 percent of all discharges from participating hospitals. ICD-10 diagnostic codes identified patients with principal diagnoses of PE and secondary diagnoses of AF. Multivariable regression analyses adjusted for extensive potential confounders, including demographics, insurance status, hospital characteristics, and over 30 individual comorbidities.

The authors acknowledge limitations inherent to administrative database research, including inability to assess illness severity at admission, potential coding errors, and lack of data on AF subtype (paroxysmal, persistent, or permanent). The study also could not determine whether AF preceded PE or developed as a consequence of the acute event—a distinction that may have prognostic significance, as suggested by prior research from the RIETE registry.

The research team outlines an ambitious agenda for future investigation, including large-scale prospective studies to confirm these findings and establish temporal relationships, mechanistic investigations using advanced imaging to characterize hemodynamic changes, and development of modified risk stratification tools incorporating AF status. Additionally, comparative effectiveness research examining optimal anticoagulation strategies and the role of rhythm control in this population would inform evidence-based clinical decision-making.
Dr. Mubarak Hassan Yusuf (corresponding author) is affiliated with the Division of Pulmonary and Critical Care at St. Joseph University Medical Center in Paterson, New Jersey. Dr. Olayiwola Akeem Bolaji is a Cardio-Oncology Fellow in the Division of Cardiology at Memorial Sloan Kettering Cancer Center, where his research focuses on cardiovascular outcomes in complex patient populations and the application of data science to clinical medicine. Co-authors Dr. Akanimo Anita and Dr. Faridat Moyosore Abdulkarim are affiliated with Lincoln Medical Center in the Bronx; Dr. Chibuike Daniel Onyejesi with University of Nigeria Teaching Hospital; Dr. Maryam Yusuf with Federal Teaching Hospital, Katsina; and Drs. Utku Ekin, Arham Syed Hazari, and Mourad Ismail with St. Joseph University Medical Center.