Microvascular Obstruction in ST-Segment Elevation Myocardial Infarction: Looking Back to Move Forward. Focus on CMR

Abstract

After a myocardial infarction (MI), despite the resolution of the coronary occlusion, the deterioration of myocardial perfusion persists in a considerable number of patients. This phenomenon is known as microvascular obstruction (MVO). Initially, the focus was placed on re-establishing blood flow in the epicardial artery. Then, the observation that MVO has profound negative structural and prognostic repercussions revived interest in microcirculation. In the near future, the availability of co-adjuvant therapies (beyond timely coronary reperfusion) aimed at preventing, minimizing, and repairing MVOs and finding convincing answers to questions regarding what, when, how, and where to administer these therapies will be of utmost importance. The objective of this work is to review the state-of-the-art concepts on pathophysiology, diagnostic methods, and structural and clinical implications of MVOs in patients with ST-segment elevation MIs. Based on this knowledge we discuss previously-tested and future opportunities for the prevention and repair of MVO.

Keywords: microvascular obstruction; myocardial infarction; reperfusion injury.

Figure 1

Mechanisms implicated in the pathophysiology of microvascular obstruction (MVO) after myocardial infarction. MVO is a multifactorial phenomenon caused by the interaction of a variety of mechanisms that act predominantly (but not only) at: Pre-reperfusion: (1) Patient factors. (2) Endothelial abnormalities. Optic (left) and electronic (right) microscopic views show diffuse microvascular endothelial damage prior to reperfusion. (3) Decreased capillary density in areas with MVO soon after ischemia onset. Reperfusion: (4) Ischemia-reperfusion injury. After 90 min ischemia in a swine model, MVO (asterisk) was macroscopically undetectable if the artery remained occluded (left) but was clearly present 1 min after reperfusion (right). (5) Embolization. Distal migration of thrombotic material (arrow) after primary angioplasty. (6) Vasoconstriction. Severe vasospasm (arrows) immediately after reperfusion. Post-reperfusion. (7) Increase in endothelial permeability. Hematoxylin-eosin staining in experimental samples (left) and T2-weighted cardiovascular magnetic resonance in patients (right) display the consequences of increased endothelial permeability; namely, edema (asterisk) and hemorrhaging. (8) External compression. Severe hemorrhage (asterisk) at the microscopic (left) and macroscopic (right) levels contribute to microvascular compression and MVO. (9) Inflammation. Massive inflammatory reaction in the core of an area with severe MVO. (10) Dynamics and repair are crucial to understanding the pathophysiology of MVO. See Section 6 for further details on this topic.

Figure 2

Coronary reperfusion and microvascular obstruction (MVO). The absence of coronary reperfusion leads to transmural infarction (left panel). A complete and prompt reperfusion of the culprit artery, ideally by percutaneous coronary intervention, reduces infarct size but may imply a certain ischemia-reperfusion injury, including MVO (central panel). Hopefully, future co-adjuvant therapies beyond reperfusion will further diminish infarct size and MVO extent, and consequently, will improve patient outcomes (right panel). Arrows point at areas with infarction and asterisks at regions with MVO.

Figure 3

Diagnostic tools to detect the presence of microvascular obstruction (MVO) in patients with ST-segment elevation myocardial infarctions. The identification of MVOs can be accomplished using different tools, classified as: widely available tools (left); catheterization lab (central): traditional angiographic indices (TIMI and TIMI frame count indices, “TIMI myocardial perfusion grade”, or “myocardial blush grade”) and new invasive indices (reserve of coronary flow velocity, the diastolic deceleration time of coronary flow velocity, or the presence of systolic flow inversion); and cardiac imaging techniques (right). See text (Section on “diagnostic tools”) for further information on each specific item. Arrows point at areas with MVO. Innate immunity cells are considered neutrophils and monocytes, whereas adaptative immunity is comprised of lymphocytes and eosinophils. CMR = cardiovascular magnetic resonance; IC = intracoronary; IV = Intravenous; PCI = primary coronary intervention; TIMI = thrombolysis in myocardial infarction.

Figure 4

Clinical and structural consequences of microvascular obstruction (MVO) as derived from cardiovascular magnetic resonance (CMR) in ST-segment elevation myocardial infarction patients. (A) A CMR after 6 months, showing that more severe left ventricular remodeling and systolic deterioration occurs in patients with MVO (lower panel) compared with those without MVO (upper panel) at 1-week CMR (adapted from 7). (B) Patients with MVO at pre-discharge display a higher rate of major adverse cardiac events (MACE; death, re-infarction, or re-admission for heart failure) during follow-up than those without MVO (updated from [24]).

Figure 5

The proposed research steps in the development of novel therapeutic opportunities to prevent, minimize, or repair microvascular obstruction following myocardial infarction.

Figure 6

Dynamics of occurrence and repair of microvascular obstruction (MVO). Asterisks point to areas with MVO (adapted from [10]).

Figure 7

Co-adjuvant therapies beyond reperfusion. Proposed answers to the WH-questions. To optimize the potential effects of any novel co-adjuvant therapies on microvascular obstruction (MVO), the timing (when), the route of administration (where), the technique (how), and the mechanism addressed (what) are crucial. Ao = aorta; IC = intracoronary; IV = intravenous; LAD = left anterior descending; LV = left ventricle; RCA = right coronary artery.