NEW ORLEANS — Coronary function testing performed in patients with symptomatic ischemia but nonobstructive arteries has a high diagnostic yield, is safe, and often leads to treatment that improves quality of life, according to the initial analysis of a prospective multicenter registry. 

Although current guidelines, such as those issued in 2024 by the European Society of Cardiology, recommend diagnostic studies in this population, the “limited” uptake of such testing is probably driven by a low expectation of success, according to Samit Shah, MD, PhD, an assistant professor of cardiology at the Yale School of Medicine in New Haven, Connecticut. Shah presented early findings from the DISCOVER INOCA registry at the 2026 annual meeting of the American College of Cardiology (ACC).

Underlying Cause of Symptoms Usually Identified

In the new study, a diagnosis of the underlying cause of ischemia in patients with nonobstructive coronary arteries, called INOCA, was reached in 94% of the 500 patients enrolled, many of whom had undergone prior diagnostic testing. The safety of the comprehensive diagnostic steps taken was “favorable,” Shah said. Most important, the diagnostic studies led to a reduction in symptoms and an improvement in quality of life.

The protocol for the eight-center registry was described in a 2024 publication. In patients with suspected ischemic heart disease, eligibility for the registry required angiographically normal coronary arteries or stenosis that did not impede blood flow. The researchers excluded people with a history of cardiomyopathy and any prior percutaneous coronary intervention.

In addition to coronary angiography, the baseline diagnostic procedures included acetylcholine testing, bolus thermodilution to assess coronary flow reserve and microvascular resistance, and intracoronary imaging with ultrasound or optical coherence tomography. 

Of those enrolled, 68.8% presented with stable angina and 28.2% presented with unstable angina and/or chest pain. More than 60% of enrolled patients had previously undergone a stress test, of which nearly one third were abnormal. A small percentage (3%) entered the study with silent ischemia.

The primary endpoint in this analysis of the registry was the diagnosis. By frequency, the most common disorder was vasospastic angina, found in 36% of patients, followed by a mixed diagnosis of vasospastic angina and coronary microvascular dysfunction in 27.8%. The third most common, at 16.8%, was coronary microvascular dysfunction. 

Less common diagnoses, representing 13.8% of the population, included symptomatic myocardial bridging, endothelial dysfunction, and heightened nociception. Some of these disorders overlapped. Less than 6% of the population had normal physiology, according to the researchers. 

In addition to the fact that a diagnosis was reached in nearly 95% of patients of those enrolled in the registry, Shah noted that it was different from the preprocedural empiric diagnosis in 89%.

Symptoms Improved Significantly Following Diagnosis

Symptoms, as measured with the Seattle Angina Questionnaire, improved at 30 days from baseline in almost all cases regardless of therapy or even in the absence of therapy. With higher scores signifying symptom reduction, the median changes from baseline were often highly significant. 

The disorders associated with reduction in symptoms after diagnosis included vasospastic angina (59.7 vs 53.7; P < .001), the mixed diagnosis of vasospastic angina and coronary microvascular dysfunction (57.6 vs 52.5; P < .008), and, when grouped together, myocardial bridging, endothelial dysfunction, and heightened nociception (61.5 vs 51.4; P < .001).

Procedural adverse events occurred in seven patients (1.4%). These involved a myocardial infarction that resulted in death in one patient, a transient stroke in one patient, a vascular access complication in one patient, a major bleed in two patients, and catheter dissections in two patients. 

Over the past 5 years, a growing number of studies have suggested that the underlying cause of INOCA and its sister condition, angina with nonobstructive coronary arteries (ANOCA), can be identified with the right sequence of comprehensive testing. The new study provides a real-world context for those findings, according to Stacey E. Rosen, MD, executive director of the Katz Institute for Women’s Health at Northwell’s Long Island Jewish Medical Center in Queens, New York, and current president of the American Heart Association. 

On the basis of this registry and previous studies, the diagnosis of INOCA “is safe, feasible, and important to patients,” said Rosen, who was invited by the ACC to serve as a discussant on DISCOVER INOCA but did not participate in the study.

Given the findings from the registry, “which represents continued progress in our understanding of INOCA,” Rosen asked, “why have we been so slow in applying these findings?” 

One issue, according to Shah, is procedural barriers, such as the fact that acetylcholine testing is not regularly performed at many centers. Clinicians must be convinced that the diagnostic yield is high and that it results in clinical benefits in order to implement protocols like that described in the registry, he said. 

Nearly 80% of the patients enrolled in the DISCOVER INOCA registry were women, an enrollment feature that Rosen praised. It also included strong representation of Black (14.1%), Hispanic (10.2%), and Asian (9.2%) patients, indicating the cohort and the diagnostic yield are representative of what can be achieved in centers where this testing is implemented, according to Shah.

The take-home message for clinicians and patients is simple, he said: “If we actually provide them a diagnosis, we can make them feel better.” 

Shah reported financial relationships with Abbott Vascular, Edwards Lifesciences, Medtronic, Phillips, Shockwave, and VahatiCor. Rosen reported no potential conflicts of interest.