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

September 1, 2026 updated by: Emir Ünal, Marmara University Pendik Training and Research Hospital

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

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
600

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • 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:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Major Adverse Pulmonary Embolism Event (MAPEE) - 30-day composite
Time Frame: 30 days
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
S1: AHA/ACC vs ESC 2019 ROC-AUC comparison (exploratory)
Time Frame: 30 days
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
Time Frame: 30 days
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
Time Frame: 30 days
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
Time Frame: 30 days
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
Time Frame: Up to 30 days
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
Time Frame: 30 days
Rate of emergency department revisit for pulmonary embolism-related complaints within 30 days of index presentation.
30 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Marmara University Pendik Training and Research Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Arzu Gundogdu, Marmara University
  • Principal Investigator: Mustafa Altun, Emergency Medicine Specialist, Marmara University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 17, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 13, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 1, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 4, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 4, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 1, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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