📋 Primary Results Presented · ACC.26 · March 2026

A Prospective Multicenter U.S. Registry to Define Coronary Vasomotor Disorders in Ischemia With Nonobstructive Coronary Arteries

94%
Diagnostic Yield
89%
Diagnoses Reclassified
500
Patients Enrolled
9
U.S. Centers
🔬

Study Status: Enrollment Complete — Active Long-Term Follow-Up

500 participants enrolled September 2022 – November 2025. Annual follow-up ongoing through 2030. NCT05288361

View on ClinicalTrials.gov →

About the Registry

Understanding Chest Pain Without Blockages

Investigator-InitiatedProspective MulticenterAbbott Vascular Supported

The DISCOVER INOCA Registry was designed to address a critical gap in cardiovascular medicine: millions of patients undergo cardiac catheterization each year but are found to have nonobstructive coronary arteries — yet continue to experience chest pain, shortness of breath, and reduced quality of life.

By performing comprehensive invasive coronary function testing across nine U.S. centers, DISCOVER INOCA provides the first large U.S. dataset to define the mechanisms, diagnostic yield, safety, and clinical impact of standardized coronary function testing in patients with INOCA.

✅ Key Inclusion Criteria

  • Referred for clinically indicated coronary angiography
  • Suspected ischemic heart disease
  • No obstructive CAD (stenosis <50%, or FFR ≥0.81 / RFR ≥0.90)
  • Written informed consent obtained

❌ Key Exclusion Criteria

  • MI within 90 days (INOCA, not MINOCA)
  • Prior PCI or CABG
  • Cardiomyopathy (LVEF <50%, HCM, amyloid)
  • Severe valvular disease or pulmonary HTN
  • Renal insufficiency (eGFR <30)
Patient experiencing chest pain

The Disease

What Is INOCA?

Ischemia with nonobstructive coronary arteries (INOCA) affects an estimated 3–4 million patients per year in the U.S. — yet many remain undiagnosed or are incorrectly reassured. INOCA encompasses several distinct physiologic disorders of the coronary circulation.

🔬
Guideline-Recognized Endotype

Coronary Microvascular Dysfunction (CMD)

Impaired function of the small coronary vessels resulting in reduced coronary flow reserve (CFR <2.5) or elevated microvascular resistance (IMR ≥25). Present as a primary or mixed diagnosis in 44.6% of DISCOVER INOCA participants.

Vasospastic Angina

Epicardial & Microvascular Vasospasm

Sudden tightening of coronary vessels triggered by acetylcholine provocation testing. Epicardial vasospasm or microvascular spasm identified in 63.8% of DISCOVER INOCA participants — often overlooked without formal testing.

🫀
Other Disorders

Myocardial Bridging & Endothelial Dysfunction

Myocardial bridging detected in 33% by angiography and 44% by intravascular imaging. Endothelial dysfunction identified in 32% of participants — frequently unrecognized without formal provocation testing.

📋
Guideline Recommendations for Coronary Function Testing

Class 2A, Level A — 2021 ACC/AHA Chest Pain Guidelines  |  Class 1, Level B — 2024 ESC Guidelines for Chronic Coronary Syndromes

Study Protocol

Comprehensive Coronary Function Testing

Every DISCOVER INOCA participant underwent a standardized, protocol-driven evaluation including acetylcholine vasoreactivity testing, bolus thermodilution physiology, and intravascular imaging — performed consistently across all nine U.S. centers.

1
Baseline Assessment
  • Symptom history & medications
  • SAQ questionnaire
  • EQ-5D-5L, PHQ-8, GAD-7
  • Written informed consent
2
Coronary Angiography
  • Confirm nonobstructive CAD
  • Core lab angiographic analysis
  • Myocardial bridging assessment
  • LVEDP measurement
3
Coronary Function Testing
  • ACh vasoreactivity testing
  • CFR & IMR (bolus thermodilution)
  • FFR & RFR (PressureWire X)
  • Diagnosis per COVADIS criteria
4
Intravascular Imaging
  • IVUS (86.8%) or OCT (9.4%)
  • Atherosclerotic plaque burden
  • Plaque morphology
  • Core lab analysis
5
Follow-Up
  • 30 days, 6 months, 12 months
  • Annual follow-up to 5 years
  • Centralized call center
  • Independent event adjudication
Enrollment: Sept 2022 – Nov 2025
30 Days ✓
6 Months ✓
12 Months — Ongoing
Annual Follow-Up 2026–2030

Primary Short-Term Results · ACC.26 · March 2026

Key Findings From 500 Patients

Presented at the American College of Cardiology Scientific Sessions (ACC.26) and submitted for publication. Results from 500 enrolled participants with adjudicated 30-day follow-up.

94%
Received a confirmed coronary vasomotor diagnosis after coronary function testing
89%
Had a change in their pre-procedure "empiric" diagnosis following coronary function testing
78%
Were female — highlighting the underserved population most affected by INOCA
>99%
Completed comprehensive coronary function testing per protocol across all 9 U.S. centers

📊 Post-Procedure Diagnosis Distribution

  • Vasospastic Angina (VSA)36.0%
  • Mixed CMD / VSA27.8%
  • Coronary Microvascular Dysfunction (CMD)16.8%
  • Other Disorders13.8%
  • Normal Physiology5.6%

Cumulative endotypes: CMD (incl. mixed) 44.6% · VSA (incl. mixed) 63.8% · Endothelial dysfunction 32% · Symptomatic myocardial bridging 17%

🛡️ Safety Profile

  • 98.6% of procedures completed without a serious adverse event or major angiographic complication
  • 1.4% procedural SAE (n=7): guide catheter dissections, ischemic stroke, vascular complications, periprocedural MI
  • 1.8% 30-day MACE (n=8/433): 1 death, 3 myocardial infarctions, 5 CV hospitalizations
  • No major bleeding events through 30 days
  • Average procedure time: 61 min including ACh testing, thermodilution, and intravascular imaging
  • 72% of participants had their medication regimen changed after the index procedure

Participating Centers

9 U.S. Sites — 500 Participants Enrolled

InstitutionInvestigatorN (%)
Yale University
New Haven, CT
Shah176 (35%)
Northeast Georgia Medical Center
Gainesville, GA
Toleva, G. Henry86 (17%)
The Christ Hospital
Cincinnati, OH
T. Henry82 (16%)
Stanford University Medical Center
Palo Alto, CA
Tremmel70 (14%)
NYU Langone Health
New York, NY
Smilowitz30 (6%)
Columbia University Irving Medical Center
New York, NY
Sardar, Prasad25 (5%)
NY-Presbyterian Brooklyn Methodist
Brooklyn, NY
Kobayashi15 (3%)
UCLA Medical Center
Los Angeles, CA
Parikh14 (3%)
Thomas Jefferson University Hospital
Philadelphia, PA
Savage5 (1%)

Baseline Characteristics (N=500)

Mean Age57 ± 12 yrs
Female Sex78%
Post-menopausal (of females)67%
Hypertension61%
Dyslipidemia72%
Diabetes Mellitus19%
Stable Angina69%
Prior Stress Test65%
SAQ Summary Score53.7 ± 19

Protocol Completion Rate

ACh Vasoreactivity Testing99.4%
Bolus Thermodilution (CFR/IMR)99.4%
Intravascular Imaging96%
✓ High protocol compliance across all 9 centers demonstrates real-world feasibility of coronary function testing in U.S. clinical practice

Scientific Contributions

Publications & Presentations

📄 Peer-Reviewed Publications
🏆 Primary Results Manuscript — In Submission

Invasive Coronary Function Testing in Patients With Ischemia With Nonobstructive Coronary Arteries: Initial Findings from the DISCOVER INOCA Registry

Shah SM, Toleva O, Henry TD, Tremmel JA, Smilowitz NR, Kobayashi Y, Parikh RV, Henry G, Savage M, Samuels B, Lerman A, Moses JW, Sardar P, Quesada O, Prasad M, Pietras C, Moore MS, Parise H, Cristea E, Lansky AJ, on behalf of the DISCOVER INOCA Investigators
In Submission · 2026
View Registry on ClinicalTrials.gov →
📋 Registry Design & Rationale

Determining the Cause of Coronary Vasomotor Disorders in Patients With Ischemia and Nonobstructive Coronary Arteries: Design and Rationale of the DISCOVER INOCA Prospective, Multicenter Registry

Shah SM, Tremmel JA, Henry TD, et al.
JSCAI · June 2024; 3(6):102046
Read Full Text →
📊 Related Publication

Diagnostic Yield and Clinical Utility of Coronary Angiography Versus Coronary Function Testing in Women With Angina and Nonobstructive Coronary Arteries

Cigarroa N, Latif N, Maayah M, et al.
Journal of the American Heart Association · October 2024; 13(19):e035852
View Publication →
🏛️ ACC.26 — American College of Cardiology · March 2026, New Orleans, LA
Featured Clinical Research · JACC 2026

A Prospective Multicenter Registry to Define Coronary Vasomotor Disorders in Ischemia With Nonobstructive Coronary Arteries: Primary Short-Term Results of DISCOVER INOCA

Shah SM, on behalf of the DISCOVER INOCA Investigators
J Am Coll Cardiol. 2026. doi:10.1016/j.jacc.2026.02.1032
View Abstract →
Abstract · JCIN 2026

DISCOVER INOCA Multicenter Registry: Insights From Invasive Coronary Function Testing

DISCOVER INOCA Investigators
JACC Cardiovasc Interv. 2026. doi:10.1016/j.jcin.2026.01.172
View Abstract →
🏙️ TCT 2026 — Transcatheter Cardiovascular Therapeutics · October 31 – November 3, 2026, San Diego, CA
Abstract #86068 · TCT 2026

Impact of Vasoreactivity Testing Sequence on Physiologic Parameters in Patients With INOCA Undergoing Coronary Function Testing: Insights From DISCOVER INOCA

Francese DP, on behalf of the DISCOVER INOCA Investigators
Accepted · TCT 2026
Abstract #86082 · TCT 2026

Operator Versus Core Laboratory Assessment of Coronary Physiology and INOCA Phenotype Classification in the DISCOVER INOCA Registry

Francese DP, on behalf of the DISCOVER INOCA Investigators
Accepted · TCT 2026
Abstract #88831 · TCT 2026

Discriminatory Performance of Microvascular Resistance Reserve and Resistance Reserve Ratio Across INOCA Endotypes: Insights From DISCOVER INOCA

Francese DP, on behalf of the DISCOVER INOCA Investigators
Accepted · TCT 2026
🏙️ TCT 2025 — Transcatheter Cardiovascular Therapeutics · October 2025, San Francisco, CA
TCT 803 · JACC Supplement 2025

Diagnostic Yield and Safety of Acetylcholine Vasoreactivity Testing: Insights from the DISCOVER INOCA Multicenter Registry

Toleva O, on behalf of the DISCOVER INOCA Investigators
J Am Coll Cardiol. 2025. doi:10.1016/j.jacc.2025.09.970
View Abstract →
TCT 779 · JACC Supplement 2025

Intravascular Imaging Assessment of Patients with Ischemia with Nonobstructive Coronary Arteries: Insights from the DISCOVER INOCA Multicenter Registry

Chamie D, on behalf of the DISCOVER INOCA Investigators
J Am Coll Cardiol. 2025. doi:10.1016/j.jacc.2025.09.950
View Abstract →
TCT 796 · JACC Supplement 2025

Epicardial Vessel Physiology in Patients with Ischemia and Nonobstructive Coronary Arteries: Insights from the DISCOVER INOCA Multicenter Registry

Dawson L, on behalf of the DISCOVER INOCA Investigators
J Am Coll Cardiol. 2025. doi:10.1016/j.jacc.2025.09.978
View Abstract →
JACC Supplement 2025

Coronary Vasomotor Disorders in INOCA: Insights from the DISCOVER INOCA Multicenter Registry

DISCOVER INOCA Investigators
J Am Coll Cardiol. 2025. doi:10.1016/S0735-1097(25)02406-4
View Abstract →
🩺 SCAI 2025 — Society for Cardiovascular Angiography & Interventions · May 2025
OR3-30 · JSCAI Supplement 2025

Radial vs. Femoral Access in Patients Undergoing Invasive Coronary Function Testing: Insights from the DISCOVER INOCA Registry

Lapetina Arroyo RJ, Smilowitz NR, Toleva O, …Lansky AJ, Shah SM
JSCAI. 2025;4(5 Supp):102726
View Full Text →
🏛️ TCT 2024 — Transcatheter Cardiovascular Therapeutics · October 2024, Washington, DC
TCT 674 · JACC Supplement 2024

Diagnosis of Coronary Microvascular Dysfunction With Invasive Coronary Function Testing: Insights From the DISCOVER INOCA Multicenter Registry

Shah SM, on behalf of the DISCOVER INOCA Investigators
J Am Coll Cardiol. 2024. doi:10.1016/j.jacc.2024.09.799
View Abstract →
TCT 677 · JACC Supplement 2024

Evaluating Ischemia With Nonobstructive Coronary Arteries Using Invasive Coronary Function Testing: Insights From the DISCOVER INOCA Multicenter Registry

Shah SM, on behalf of the DISCOVER INOCA Investigators
J Am Coll Cardiol. 2024. doi:10.1016/j.jacc.2024.09.796
View Abstract →
JACC Supplement 2024

DISCOVER INOCA Multicenter Registry: Procedural Characteristics and Safety of Invasive Coronary Function Testing

DISCOVER INOCA Investigators
J Am Coll Cardiol. 2024. doi:10.1016/j.jacc.2024.09.802
View Abstract →
🌍 ESC 2024 — European Society of Cardiology Congress · August 2024, London, UK
Abstract · Eur Heart J Supplement 2024

Symptom Assessment and Angina Classification of Patients with Ischemia and Nonobstructive Coronary Arteries Undergoing Invasive Coronary Function Testing: From the DISCOVER INOCA Multicenter Registry

Shah S, Tremmel JA, Henry TD, Smilowitz NR, Prasad M, Kobayashi Y, Henry G, Samuels BA, Lerman A, et al.
Eur Heart J. 2024;45(Supp 1):ehae666.1617
View Full Text →
Dr. Amir Lerman

In memory of Dr. Amir Lerman, M.D. (Mayo Clinic, 1957–2026), whose pioneering work transformed our understanding of ischemic heart disease and endothelial function. The investigators of DISCOVER INOCA dedicate this study to his vision and enduring scientific legacy. Read his tribute →

Leadership

Study Team

National Co-Principal Investigators
National Co-PI
Dr. Alexandra Lansky
Yale University · New Haven, CT
National Co-PI
Dr. Samit Shah
Yale University / VA Connecticut Healthcare System · New Haven, CT
Site Investigators
Site Investigator · Yale University
Dr. Samit Shah
New Haven, CT
Site Investigator · The Christ Hospital
Dr. Timothy Henry
Cincinnati, OH
Site Investigator · Stanford University
Dr. Jennifer Tremmel
Palo Alto, CA
Site Investigator · NYU Langone Health
Dr. Nathaniel Smilowitz
New York, NY
Site Investigator · Northeast Georgia Medical Center
Dr. Olga Toleva
Gainesville, GA
Site Investigator · NY-Presbyterian Brooklyn Methodist
Dr. Yuhei Kobayashi
Brooklyn, NY
Site Investigator · UCLA Medical Center
Dr. Rushi Parikh
Los Angeles, CA
Site Investigator · Columbia University Irving Medical Center
Dr. Partha Sardar
New York, NY
Site Investigator · Thomas Jefferson University Hospital
Dr. Michael Savage
Philadelphia, PA

🏛️ Sponsor

Yale Cardiovascular Research Group
Yale University School of Medicine
New Haven, Connecticut

💊 Funding

Investigator-initiated research grant to Yale University from Abbott Vascular. The funding source was not involved in study design or implementation.

⚙️ Study Operations

Cody Pietras — Executive Director
Kyna Henrici — Project Manager
Dr. Nida Latif — Call Center Director
Miranda Moore — Statistician
Dr. Ecaterina Cristea — Core Lab Director

Get In Touch

Contact the Study Team

For questions about DISCOVER INOCA, patient participation, media inquiries, or research collaboration, please reach out to our study team at Yale University.

Find a Participating Site →

📧 Study Email

discoverinoca@yale.edu

General inquiries, patient questions, collaboration

🏥 For Patients

The registry is currently in the follow-up phase. Contact the nearest site investigator for questions about long-term follow-up participation.

📋 ClinicalTrials.gov

NCT05288361

Full protocol, site listings, and study status