Microvascular and Endothelial Dysfunction Found in Nonculprit Artery In Over Ninety Percent of STEMI Patients, According to a Study

Findings of a study published in Circulation: Cardiovascular Interventions reflected that microvascular and endothelial dysfunction in the non-culprit artery territory in patients with STEMI were very common. Additionally, in 93% of the patients, functional abnormalities were found. Moreover, the investigators of the study also concluded that acetylcholine administration in the early phase post-STEMI in patients with multivessel disease was safe.

An article by Gibson et al. on TIMI frame count published in Circulation in 1996 had shown that flow in non-culprit arteries routinely used to grade TIMI flow could not be presumed to be normal, as demonstrated by the 21% reduction in flow in these arteries at 90 minutes after thrombolysis. Despite high rates of TIMI grade 3 flow reported in the literature, only a third of patients with an open artery actually achieved a flow that was truly within the normal range (CTFC ≤27). The study also supported the idea that the disordered microvasculature tone played a crucial role in flow delays immediately following thrombolysis. A subsequent publication by Dr. C. Michael Gibson and his colleagues published in the Journal of the American College of Cardiology in 1999 drew the conclusion that flow in non-culprit arteries was slowed by 45% at 90 min after thrombolytic administration, and slower non-culprit artery flow was linked to slower culprit artery flow. Moreover, relief of the residual stenosis in the culprit artery restored flow that was equal to that observed in the non-culprit artery, but the resulting culprit artery flow was still slower than normal. Acute MI reduced flow globally, and slower global flow was associated with adverse clinical outcomes. However, further elaborating on the role of the microvasculature, the article stated, “It may be speculated that delayed non-culprit artery flow may be the result of more extensive necrosis in shared microvasculature, or occur as a consequence of vasoconstriction, perhaps mediated by local neurohumoral reflexes.”

It is estimated that approximately half of the patients presenting with ST-segment–elevation myocardial infarction (STEMI) have multivessel disease. The physiology of the non-culprit artery has not been thoroughly studied to date. The identification of microvascular or endothelial dysfunction in patients with coronary artery disease has prognostic implications. Microvascular dysfunction in the infarct-related territory is common after revascularization. Safety concerns exist regarding acetylcholine administration in the early phase post–ST-segment–elevation myocardial infarction. Therefore, the investigators of the FISIOIAM Study sought to characterize the coronary physiology of the non-culprit artery in the early phase after STEMI and determine the real prevalence of microvascular and endothelial dysfunction. The study was designed as an observational single-center study where patients with STEMI and other coronary artery lesions in a different territory were prospectively included. The protocol took place following revascularization of the culprit artery and comprised of 3 phases: first, epicardial endothelial functional assessment using intracoronary acetylcholine; second, epicardial severity quantification based on fractional flow reserve, and nonendothelial microvascular function with coronary flow reserve and the index of microvascular resistance; third, endothelium-dependent microvascular function assessment based on the endothelial coronary flow reserve. A total of eighty-four patients were included. The mean age was 62±10 years, and 86.9% of the subjects were men. Felipe Díez-Delhoyo and his team reported that only 6 subjects had a nonpathological study: macrovascular endothelial dysfunction was present in 60% of the patients; fractional flow reserve ≤0.8, coronary flow reserve <2, and an index of microvascular resistance >25 were evident in 34%, 37%, and 28% of the subjects respectively; and microvascular endothelial dysfunction (endothelial coronary flow reserve <1.5) was observed in 44%. They also noted that in-hospital mortality was 0%, and no major complications occurred. Lastly, at the 6-month follow-up, there were no events related to the non-culprit artery.

The team of investigators concluded that microvascular and endothelial dysfunction in the non-culprit territory after myocardial infarction were very common. Globally, 93% of patients with myocardial infarction have functional abnormalities in the non-culprit territory. Moreover, acetylcholine administration in the acute phase post–ST-segment–elevation myocardial infarction was safe. Speaking of the importance of his study, primary investigator Dr. Felipe Díez-Delhoyo stated, “To the best of our knowledge, the FISIOIAM is the first study to date to perform a comprehensive analysis of the non-culprit artery physiology in the setting of a STEMI. We conducted the study to evaluate the endothelium-dependent and endothelium-independent response, both in the macro and microvascular compartments. This study has shown that it is feasible and safe to comprehensively investigate the physiology of the non-culprit artery shortly after a STEMI. The second important finding of the study is that most subjects presenting with STEMI and multivessel disease have an abnormal macrovascular or microvascular function.” Referring to certain peculiarities in the findings, he added, “We studied differences in physiological parameters in 2 specific subgroups: women versus men, and vessels with ischemic versus nonischemic FFR. Women showed no significant differences in microvascular and endothelial parameters compared with men. There was a nonsignificant trend towards a lower CFR, but IMR was equal between groups, which is consistent with previous findings in patients without obstructive coronary disease. This discrepancy between CFR and IMR underscores the importance of microvascular resistance to specifically diagnose microvascular function.”