Microvascular Dysfunction an Important Independent Contributor to Heart Disease

Coronary microvascular dysfunction (CMD) was an important independent component of ischemic heart disease, though it often accompanied epicardial coronary artery disease, a prospective study showed.

In a large, unselected population undergoing clinically indicated invasive coronary angiography (ICA) in routine practice for suspected ischemic heart disease, microvascular dysfunction was associated with higher 2-year estimated risk of the composite endpoint of all-cause death, myocardial infarction, clinically-driven repeat revascularization, or hospitalization for heart failure (18.8% vs 10.5% without CMD, HR 1.91, 95% CI 1.22-2.99).

While particularly common among patients with obstructive epicardial coronary artery disease (21.5% vs 9.3% without obstructive disease), CMD carried an even more elevated outcome risk in people without obstructive epicardial coronary disease (31.4% vs 9.0%, HR 3.45, 95% CI 1.69-7.06), reported Joo Myung Lee, MD, MPH, PhD, of Samsung Medical Center in Seoul, at the EuroPCR meeting in Paris.

Lee’s FLOW-CMD registry study, which included seven Korean sites and over 1,000 participants, was simultaneously published in The Lancet.

The report also noted that patients with CMD tended toward worse angina profiles after percutaneous coronary intervention (PCI) than their non-CMD peers, although without reaching statistical significance.

“This observation is consistent with previous studies suggesting coronary microvascular dysfunction as a potential mechanism underlying persistent angina after PCI. Therefore, evaluation of coronary microvascular function might help to identify mechanisms underlying patients’ symptoms beyond epicardial coronary artery disease, particularly in the context of clinical presentation and suspected ischaemic heart disease,” Lee’s group wrote.

CMD reflects functional or structural abnormalities of the coronary microcirculation. It is one of several pathologies that could lead to “INOCA,” an umbrella term for any ischemia with no obstructive coronary artery disease. Notably, current guidelines only give microvascular function testing a weak class IIa endorsement, and primarily when obstructive epicardial disease is not present.

Then there is the unanswered question of how to manage CMD. Generally, the focus has been on managing symptoms and reducing long-term cardiovascular risks.

During a press conference, Lee acknowledged that there is no therapy for CMD per se, but affected patients can take treatments “correcting the underlying cause,” such as high-intensity statins for coronary atherosclerotic disease.

Last year, however, the WARRIOR trial was unable to prove that a strategy of statins coupled with lisinopril or losartan was any good for preventing major adverse cardiovascular events in symptomatic women with suspected INOCA. Major caveats of that study include subpar patient adherence to assigned therapies and COVID-19-era issues such as a trial shutdown for 6 months.

“Further studies are needed to establish whether targeting CMD improves clinical outcomes,” Lee and colleagues urged.

Their prospective, observational study included consecutive individuals who had been referred for clinically indicated ICA from 2022 to 2024. Those who had intermediate epicardial coronary artery stenosis (40-90% by visual estimation) underwent comprehensive physiologic assessment. Patients with multivessel disease and at least one lesion with intermediate stenosis were included, whereas people with a single severe stenosis were excluded.

Thus, out of 5,764 individuals screened, 1,003 were enrolled in the study and followed over a median 1.9 years. This cohort had a median age of 65 years, and about 75% of participants were men. Initial presentations were chronic coronary syndrome in 66.2% and acute coronary syndrome in 33.8%. The initial symptom was most commonly typical chest pain on exertion (63.3%).

Before ICA, 47.7% of the group had undergone noninvasive tests, with abnormal results in 95.6% of those tested. On ICA, 43.4% ended up having multivessel disease, 40.5% single-vessel disease, and 16.2% insignificant stenosis.

The present study defined CMD as coronary flow reserve <2.0 and an index of microcirculatory resistance ≥25.

Patients with CMD more frequently had FFR ≤0.80 (60.7% vs 41.1% of those with preserved microvascular function) and underwent PCI (71.8% vs 44.6%), according to Lee’s group.

Study authors noted the limited generalizability of their findings to patients with normal coronary arteries or minimal disease and people outside South Korea. There was also a potential source of misclassification from coronary physiological assessments being mostly taken from a single vessel rather than across all major coronary territories, they acknowledged.