NEW ORLEANS — An evaluation of myocardial blood flow with stress perfusion cardiac magnetic resonance (CMR) imaging after a negative angiogram changed the presumed diagnosis and treatment in the majority of patients in a randomized double-blind trial.

“Endotyping-informed therapy in the MRI-guided intervention arm led to a reduction in angina burden and an improvement in health-related quality of life,” reported the principal investigator Colin Berry, MBChB, PhD, a professor of cardiology and imaging at the University of Glasgow, Glasgow, Scotland.

The results of the late-breaking CorCMR trial were presented at American Heart Association (AHA) 2025 Scientific Sessions 2025. The findings were simultaneously published in Nature Medicine.

CMR Reclassified Diagnosis in More Than Half of the Patients

For the study, Berry and colleagues enrolled 250 patients presenting with chest pain who did not have obstructed coronary arteries on angiogram at three centers in the UK. All underwent a stress perfusion CMR with myocardial blood flow mapping. The randomization took place after angiography ruled out obstructive disease.

In almost all patients (97.6%), the presumed diagnosis after the negative angiogram was noncardiac chest pain, but CMR led to a reclassification in 53% of them (95% CI, 46.6-59.3).

In the intervention group, the management team was provided with the CMR results to guide care. For the control group, the CMR results were withheld, and subsequent management was performed with usual care.

After CMR, the diagnosis of noncardiac chest pain was upheld in only 47% of them. Fifty-one percent of patients were diagnosed with microvascular angina and 0.4% had vasospastic angina. Cardiomyopathy and myocarditis were incidental findings in two patients in each group.

The change in the initial diagnosis was the primary outcome of this diagnostic study. The secondary outcomes included control of angina, measured by the Seattle Angina Questionnaire (SAQ), and change in quality of life, measured by the five-dimension EuroQoL-5 assessment, at 12 months relative to baseline and between study groups.

At 12 months, the SAQ score improved by a mean of 21.7 points in the intervention group but remained essentially unchanged, down 0.8 points, in the control group. Differences in medical therapy are the likely explanation, according to Berry.

For those in the intervention group relative to the control group, anti-anginal therapies (84% vs 64%; P = .001), aspirin (77% vs 56%; P < .001), and statins (82% vs 62%; P = .001) were all offered more frequently.

The high diagnostic yield of CMR for patients who otherwise would have been discharged with a diagnosis of noncardiac chest pain was consistent across patient groups, Berry said.

“These results apply equally by sex but are perhaps particularly relevant to women because microvascular angina associates more commonly with women presenting with chest pain,” he said.

Data Said to Have Immediate Clinical Relevance

The data from CorCMR have immediate clinical relevance, according to Robert A. Harrington, MD, a cardiologist currently serving as dean of Weill Cornell Medicine and provost for Medical Affairs at Cornell University in New York City. He noted the study employed a “clever study design” to address “a common and important clinical problem.”

“This is a strategy we can use routinely for those with INOCA [ischemia with nonobstructed coronary arteries],” Harrington said.

As the second most common reason for emergency department visits among adults, chest pain is an important target for better and more efficient diagnostic strategies, according to Berry. He cited data suggesting that only half of the patients with chest pain are diagnosed with a cardiac cause, but CorCMR data suggest many of these are likely sent home despite cardiovascular pathology.

Based on the CorCMR data, “coronary angiography should include a functional test either invasively or noninvasively” to capture these patients, he maintained.

Janet Wei, MD, co-director of the Stress Echocardiography Lab at Cedars-Sinai Medical Center in Los Angeles, suggested these data coupled with those from other studies are “changing the paradigm of how we manage patients who present with ischemia.”

The importance of separating patients with a negative angiogram who have cardiac disease from those who do not is that INOCA “is not a benign condition,” Wei said. “It is associated with increased major adverse cardiac events as well as increased healthcare costs related to repeat testing.”

Because there has been no systematic approach to identify causes of noncardiac chest pain, delays in identifying the true cause of INOCA can often be measured in years, Wei reported.

“INOCA is associated with significant impairments in quality of life, whether it is the physical health, mental health, or social health,” she said.

This study has not resolved which protocol is best for establishing INOCA and its cause in patients presenting with chest pain, according to Wei, but it does show that taking an extra step to look for INOCA results in improvements in angina symptoms and quality of life.

The CorCMR trial was an investigator-initiated study without industry funding. Berry reported financial relationships with Abbott Vascular, AskBio, AstraZeneca, Boehringer Ingelheim, CorFlow, Edwards Lifesciences, MAIA Pharmaceuticals, Merck, Novartis, Servier, Xylocor, and Zoll Medical. Harrington reported financial relationships with Atropos, Azuma, Basking Biosciences, Bitterroot Bio, Bristol-Myers Squibb, Bridge Bio, Chiesi, CSL Behring, Edwards Lifesciences, Element Science, Foresight, and Merck. Wei reported a financial relationship with Abbott Vascular.