SAN FRANCISCO — In patients with suspected myocardial infarction (MI) with nonobstructive coronary lesions, an intensive approach to diagnosis and subsequent tailored treatment based on the underlying cause improved angina, according to new data.

In the randomized PROMISE trial, researchers found that most initial presumed etiologies of myocardial infarction with nonobstructive coronary arteries (MINOCA) are incorrect, risking suboptimal management. Following a comprehensive diagnostic assessment, the initial suspected diagnosis was reclassified in 75.5% of cases, management was adjusted, and angina-related health status was improved at 12 months, reported Rocco A. Montone, MD, PhD, an interventional cardiologist in the Department of Cardiovascular Sciences at the Fondazione Policlinico, Rome.

MINOCA represents 6%-10% of all MIs that undergo angiography, and the heterogenous causes are a diagnostic challenge, according to Montone. The known underlying etiologies of the umbrella term MINOCA include unstable plaque, spontaneous coronary artery dissection, epicardial spasm, microvascular spasm, and embolism.

The lack of an evidence-based diagnostic algorithm to distinguish between and treat these underlying etiologies was the basis for PROMISE — the first randomized trial addressing this diagnostic challenge, according to Montone.

The results of PROMISE were presented in a late-breaking clinical science session at the Transcatheter Cardiovascular Therapeutics (TCT) 2025 meeting. The study was published simultaneously in the European Heart Journal. 

MINOCA Is Not Now Addressed Systematically

In this open-label study, 101 patients hospitalized with MINOCA — defined as a stenosis greater than 50% — were randomly assigned to a comprehensive diagnostic approach or standard of care. All were scheduled for angiography. The comprehensive approach included a variety of imaging, such as coronary magnetic resonance and optical coherence tomography, as appropriate to identify and stratify therapy based on the underlying cause. In the standard care group, the usual diagnostic protocol and therapy for MI was employed.

The primary endpoint was angina status at 12 months as assessed by the Seattle Angina Questionnaire Summary Score (SAQSS), for which higher scores signal less angina and better quality of life. The secondary endpoint was a composite of major adverse cardiovascular events (MACE), including all-cause death, MI, stroke, heart failure hospitalization, or repeated coronary angiography.

Of the 101 patients, 92 had confirmed MINOCA and were the focus of the randomized comparison. 

Among these, the SAQSS angina score was significantly higher among those who underwent a comprehensive workup at 12 months, with a mean between-group difference of 9.38 points favoring the intensive approach over standard of care (P < .001). From baseline, the SAQSS score increased an average of 12.3 points in the intervention group vs 2.9 points in the standard of care group.

An increase of at least 5 points in SAQSS is considered clinically meaningful, according to Montone.

The lower rate of MACE at 12 months (2.2% vs 8.5%; P = .18) did not reach statistical significance.

Cause of Disease Is Reclassified in 75%

The underlying etiology of MINOCA was identified in 80% of the patients who underwent the comprehensive evaluation. Relative to the initial suspected etiology, the cause was reclassified in 75.5% of patients.

Atherosclerotic plaque instability was suspected in 60.6% of patients but confirmed in just 22.2% (P < .001). Conversely, epicardial spasm was suspected in just 13.3% but confirmed in 35.6% (P = .006). Microvascular spasm was not a suspected etiology in any patient, but it was confirmed in 4.4%. Coronary spasm was suspected and confirmed in two patients, and the greater rate of confirmed compared with suspected spontaneous coronary artery dissection was nonsignificant (13.3% vs 8.9%; P = .5).

The lower rate of angina at 12 months was accompanied by significant reduction in all components of angina, including limitation on activities (P = .001), stability (P < .001), and frequency (P < .001). These were accompanied at 12 months by significantly higher rates of treatment satisfaction (P < .001) and improved quality of life (P = .003).

Unlike the individualized therapy in the group undergoing comprehensive assessment, the standard care group received usual post-MI care, such as antiplatelet therapy, statins, and beta blockers. Montone pointed out that these therapies might not be sufficient or even contraindicated for some MINOCA etiologies. As an example, he said beta blockers have the potential to exacerbate vasospastic angina.

The fact that no etiology could be detected in 20% of patients suggests the full scope of causes is still not understood, Montone reported.

The main message from this trial, according to Montone, is that a protocol to identify and treat the underlying etiology of MINOCA improves outcomes at 12 months. No protection against hard events was seen, but Montone said that the numerical difference in MACE makes a larger trial attractive.

Data regarding an approach to MINOCA are important, according to Sanjit Jolly, MD, a professor of medicine and an interventional cardiologist at McMaster University in Hamilton, Canada. He said the problem has become more common with more sensitive diagnostics, but “we have not had guidance or data on what to do.”

Yet, due to its size, Jolly characterized PROMISE “as a first step.” While reducing angina symptoms at 12 months is a clinical benefit, “I think what we want to know is whether [individualized therapy] can prevent recurrent events,” he said.

One problem is that the comprehensive diagnostic studies employed in this trial cannot generally be performed in the cath lab, so this will evolve an extra step, according to Evelyn Regar, MD, PhD, an interventionalist affiliated with Ludwig-Maximilians Hospital in Munich, Germany. Nonetheless, she considers this work “exciting.”

“It reflects a paradigm shift in interventional cardiology. We are going away from angiography to only look for narrowing. We are very much more looking for pathophysiology with way better tools and we are finding new targets, and I think this is very much a reflection of that.”

The PROMISE trial was investigator-initiated. Montone and Regar reported no potential conflicts of interest. Jolly reported financial relationships with Abiomed, Boston Scientific, Penumbra, Shockwave, and Teleflex.