Prognostic Value of 2026 AHA/ACC Clinical Categorization in Acute Pulmonary Embolism Patients Presenting to the Emergency Department (APEX-2026)

Prognostic Value of the 2026 American Heart Association/American College of Cardiology (AHA/ACC) Clinical Categorization System (Categories A-E) for Predicting 30-Day Major Adverse Pulmonary Embolism Events (MAPEE) in Patients Presenting to the Emergency Department With Acute Pulmonary Embolism: A Prospective Observational Cohort Study

Background: The 2026 American Heart Association/American College of Cardiology (AHA/ACC) Pulmonary Embolism Guideline (Creager et al., Circulation 2026) introduced a novel five-category (A-E) clinical classification system with subcategories and an R modifier, replacing prior risk stratification frameworks. Prospective validation of this classification system using composite clinical outcomes is lacking. Objective: To evaluate the prognostic value of the 2026 AHA/ACC clinical categorization (Categories A-E plus R modifier) for predicting 30-day Major Adverse Pulmonary Embolism Events (MAPEE) in emergency department (ED) patients with acute pulmonary embolism (PE). Methods: Prospective observational cohort study conducted at Marmara University Faculty of Medicine Emergency Department, enrolling 600 consecutive adult patients with confirmed acute PE by computed tomography (CT) pulmonary angiography between April 2026 and January 2027. Primary outcome: MAPEE composite (all-cause mortality OR hemodynamic deterioration OR treatment escalation OR cardiopulmonary resuscitation) within 30 days. Secondary outcomes include area under the receiver operating characteristic curve (AUC) comparison with the European Society of Cardiology (ESC) 2019 risk stratification (exploratory), negative predictive value (NPV) of low-risk categories (A+B) for safe discharge, MAPEE trend across C1/C2/C3, and R modifier odds ratio. Statistical analysis: Jamovi v2.x. Reporting follows the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) 2007 checklist.

Study Overview

• Status: Recruiting
• Conditions: Venous Thromboembolism; Pulmonary Embolism; Acute Pulmonary Embolism
• Intervention / Treatment: Other: 2026 AHA/ACC Clinical Risk Categorization

Detailed Description

STUDY DESIGN: Single-center prospective observational cohort. No intervention applied. Patients managed per standard of care. SETTING: Marmara University Pendik Training and Research Hospital Emergency Department, Istanbul, Turkey. Annual ED census approximately 200,000 visits. STUDY POPULATION: Adult patients (18 years or older) presenting to the ED with confirmed acute PE on computed tomography (CT) pulmonary angiography, enrolled consecutively from April 2026 to January 2027 (anticipated enrollment period 10 months). EXPOSURE: 2026 AHA/ACC PE clinical category assigned independently by two trained emergency physicians at presentation. Categories: A (subclinical/incidental), B (symptomatic, low severity; Pulmonary Embolism Severity Index (PESI) I-II / simplified PESI (sPESI)=0), C1/C2/C3 (elevated severity; stratified by right ventricular (RV) dysfunction and cardiac biomarkers), D1/D2 (incipient cardiopulmonary failure), E1/E2 (established cardiopulmonary failure). R modifier applied when hypoxemia/tachypnea/escalating oxygen requirement present without meeting higher category criteria. PRIMARY OUTCOME - MAPEE (Major Adverse Pulmonary Embolism Event): composite endpoint defined as occurrence of any of the following within 30 days: (1) All-cause mortality, (2) Hemodynamic deterioration (systolic blood pressure (SBP) less than 90 mmHg for at least 15 minutes or vasopressor requirement), (3) Treatment escalation (systemic thrombolysis, catheter-directed therapy, surgical embolectomy, or extracorporeal membrane oxygenation (ECMO)), (4) Cardiopulmonary resuscitation. Expected event rate: 12% (n approximately 59 events out of 492 analyzable patients after 18% attrition from 600 gross enrollment). SAMPLE SIZE RATIONALE: Based on the Hanley-McNeil variance formula (Hanley and McNeil, Radiology 1982;143:29-36). H0: AUC=0.65 (minimum clinically meaningful discrimination); H1: AUC=0.80 (supported by published composite-outcome AUC values for comparable systems: PESI 0.84, Bova score 0.82, Hestia criteria SROC 0.81); two-sided alpha=0.05. At the planned n_gross=600 enrollment (n_net=492 analyzable, 59 expected events, 433 non-events), the design provides approximately 97.6% power for H1=0.80 using the standard single-proportion Hanley-McNeil test (a conservative pooled-variance sensitivity approach yields approximately 79.2%; the sample size is considered adequate under either method). Minimum detectable AUC at 80% power is approximately 0.761. Events per variable (EPV) = 59/5 = 11.8, supporting multivariable models with up to 5 predictor variables (EPV of at least 10 recommended per Peduzzi et al. 1996). DeLong AUC comparison (AHA/ACC 2026 vs ESC 2019, secondary outcome S1) will require substantially larger samples for adequate power given the two correlated ROC curves; this comparison is designated exploratory/hypothesis-generating and will not be used for confirmatory inference. STROBE COMPLIANCE: This study follows the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) 2007 checklist for reporting of observational studies.

• Study Type: Observational
• Enrollment (Estimated): 600

Contacts and Locations

• Study Contact: Name: Emir Ünal, Assistant Professor; Phone Number: 7023 +90 216 657 06 06; Email: emirunal@gmail.com

Study Locations

• Turkey (Türkiye)
  • Istanbul, Turkey (Türkiye), 34899
    • Recruiting
    • Marmara University Pendik Training and Research Hospital
    • Contact: Emir Ünal; Phone Number: +90 216 657 06 06; Email: emirunal@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult patients (>=18 years) presenting to Marmara University Pendik Training and Research Hospital Emergency Department with confirmed acute pulmonary embolism on CTPA between April 2026 and January 2027.

Description

Inclusion Criteria:

1. Age >=18 years
2. Confirmed acute PE on CT pulmonary angiography (CTPA) within 24 hours of ED presentation
3. Informed consent obtained
4. Ability to complete 30-day follow-up

Exclusion Criteria:

1. Chronic thromboembolic pulmonary hypertension (CTEPH)
2. Age <18 years
3. Pregnancy
4. Incomplete CTPA or non-diagnostic imaging
5. Prior PE within 3 months
6. Refusal of informed consent
7. Inability to complete 30-day follow-up (no phone/address)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Acute PE Cohort - AHA/ACC 2026 Categories A-E + R modifier; All consecutive adult patients presenting to the emergency department with confirmed acute pulmonary embolism, assigned to 2026 AHA/ACC clinical categories (A-E) plus right ventricular strain (R) modifier at presentation. No study intervention is assigned; all patients are treated per standard of care per treating clinician judgment.

Other: 2026 AHA/ACC Clinical Risk Categorization; Not a therapeutic intervention. Refers to the 2026 AHA/ACC clinical categorization framework (Categories A-E plus R modifier for right ventricular strain) applied at presentation to prognostically classify patients with confirmed acute pulmonary embolism. All patients are managed per standard institutional practice; no protocol-driven treatment or diagnostic assignment is made based on this categorization.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Adverse Pulmonary Embolism Event (MAPEE) - 30-day composite	Composite of: (1) all-cause mortality, OR (2) hemodynamic deterioration (SBP <90 mmHg for >=15 minutes or vasopressor requirement), OR (3) treatment escalation (systemic thrombolysis, catheter-directed therapy, surgical embolectomy, or ECMO), OR (4) cardiopulmonary resuscitation - within 30 days of ED presentation.	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
S1: AHA/ACC vs ESC 2019 ROC-AUC comparison (exploratory)	Comparison of ROC-AUC: 2026 AHA/ACC A-E system vs ESC 2019 risk stratification for MAPEE prediction (DeLong test - EXPLORATORY/hypothesis-generating; n=600 enrollment marginally below the 621 required for 80% power at H1=0.80; no superiority claim will be made).	30 days
S2: NPV of AHA/ACC Category A+B for MAPEE	Negative Predictive Value (NPV) of AHA/ACC Category A+B for MAPEE, evaluating potential for safe emergency department discharge without hospital admission.	30 days
S3: MAPEE trend across AHA/ACC subcategories C1, C2, C3	Linear MAPEE event rate trend across AHA/ACC subcategories C1, C2, and C3, assessed via Cochran-Armitage trend test.	30 days
S4: Odds ratio for MAPEE by R modifier status	Odds ratio (OR) and likelihood ratio (LR+/LR-) for MAPEE in patients with vs without the R modifier (right ventricular strain) at presentation.	30 days
S5: Intensive care unit (ICU) admission rate by AHA/ACC category	ICU admission rate within 30 days of ED presentation, stratified by 2026 AHA/ACC clinical category at presentation.	Up to 30 days
S6: 30-day ED revisit rate for PE-related complaints	Rate of emergency department revisit for pulmonary embolism-related complaints within 30 days of index presentation.	30 days

Collaborators and Investigators

• Sponsor: Marmara University Pendik Training and Research Hospital
• Investigators: Principal Investigator: Arzu Gundogdu, Marmara University; Principal Investigator: Mustafa Altun, Emergency Medicine Specialist, Marmara University

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: August 13, 2026
• First Submitted That Met QC Criteria: September 1, 2026
• First Posted (Actual): September 4, 2026

Study Record Updates

• Last Update Posted (Actual): September 4, 2026
• Last Update Submitted That Met QC Criteria: September 1, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: risk stratification; AHA/ACC guidelines; MAPEE
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Respiratory Tract Diseases; Lung Diseases; Embolism and Thrombosis; Embolism; Thromboembolism; Pulmonary Embolism; Venous Thromboembolism
• Other Study ID Numbers: 09.2026.26-0432

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No plan to share individual participant data at this time; data sharing decisions will be reconsidered upon study completion and publication.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No