Definition/Introduction

Acute myocardial infarction (MI) is the leading cause of death worldwide. It has been widely accepted that it is due to the insufficient blood supply to the cardiac tissue. In an attempt to intervene, physicians in the 1970s studied ligation of canine coronary arteries and documented prevention of necrosis with ligation release under appropriate time limits. Initial therapeutic reperfusion was established using intravenous and intracoronary thrombolytic agents, and several studies were conducted on them.[1][2][3][4]

Clinical Significance

In 1983, the TIMI (Thrombolysis in Myocardial Infarction) study group (Brigham and Women's Hospital, Boston, Massachusetts) chose to conduct a randomized, double-blind, multicenter study to assess the efficacy of intravenous (IV) streptokinase. Phase 1 studied IV streptokinase and IV tPA (tissue plasminogen activator) and assessed "recanalization of the totally occluded artery 90 minutes after the start of drug infusion." For this study, the TIMI Coronary Grade Flow was established to ensure a uniform and consistent method of recording epicardial perfusion on coronary arteriography. TIMI grade flow 0 represented total occlusion, and TIMI grade flow 3 represented normal epicardial perfusion. Images were evaluated at the clinical site and later at a central radiographic lab to further ensure consistency. In 1985, due to statistically significant differences in recanalization rates with tPA over streptokinase, phase 1 of the study was stopped.[5][6][7]

Definitions of Perfusion

• Grade 0 (no perfusion): There is no antegrade flow beyond the point of occlusion.
• Grade 1 (penetration without perfusion): The contrast material passes beyond the area of obstruction but “hangs up” and fails to opacify the entire coronary bed distal to the obstruction for the duration of the cine-angiographic filming sequence.
• Grade 2 (partial perfusion): The contrast material passes across the obstruction and opacifies the coronary bed distal to the obstruction. The rate of entry of the contrast material into the vessel distal to the obstruction or the rate of clearance from the distal bed is perceptibly slower than its entry into or clearance from comparable areas not perfused by the previously occluded vessel—e.g., the opposite coronary artery or the coronary bed proximal to the obstruction.
• Grade 3 (complete perfusion): Antegrade flow into the bed distal to the obstruction occurs as promptly as antegrade flow into the bed proximal to the obstruction, and clearance of contrast material from the involved bed is as rapid as clearance from an uninvolved bed in the same vessel or the opposite artery.

Limitations of the TIMI grade flow include observer variability, and it only provides categorical values instead of continuous ones. However, the TIMI study group also developed additional scoring systems. TIMI frame count (TFC) measures the number of cine-angiographic frames to reach standardized distal landmarks, thus providing a quantitative assessment of epicardial flow. It was established to enhance the reproducibility of the angiographic assessment.

As TIMI grade flow and TFC assess epicardial flow, TIMI myocardial perfusion (TMP) grade was developed to assess microvascular perfusion. Using myocardial contrast echocardiography, a visual assessment is made of contrast density in the infarcted myocardium after reperfusion therapy. It is scored 0 to 3, with “0 representing no apparent tissue-level perfusion and TMP 3 indicating normal perfusion.” It has been shown that despite having a TIMI grade flow of 3, some patients have no reflow in the myocardium (TMP 0). TMP has also been shown to be an independent predictor of mortality.[8][6]

Definitions of TMP Grades

• TMP Grade 0: Failure of dye to enter the microvasculature. Either minimal or no ground-glass appearance (“blush”) or opacification of the myocardium in the distribution of the culprit artery, indicating lack of tissue-level perfusion.
• TMP Grade 1: Dye slowly enters but fails to exit the microvasculature. There is the ground-glass appearance (“blush”) or opacification of the myocardium in the distribution of the culprit lesion that fails to clear from the microvasculature, and dye staining is present on the next injection (approximately 30 seconds between injections).
• TMP Grade 2: Delayed entry and exit of dye from the microvasculature. There is a ground-glass appearance or opacification of the myocardium in the distribution of the culprit lesion that is strongly persistent at the end of the washout phase (i.e., the dye is strongly persistent after three cardiac cycles of the washout phase and either does not or only minimally diminishes in intensity during washout).
• TMP Grade 3: Normal entry and exit of dye from the microvasculature. There is the ground-glass appearance (“blush”) or opacification of the myocardium in the distribution of the culprit lesion that clears normally and is either gone or only mildly/moderately persistent at the completion of the washout phase (i.e., dye is gone or is mildly/moderately persistent after 3 cardiac cycles of the washout phase and noticeably diminishes in intensity during the washout phase), similar to that in an uninvolved artery. The blush that is of only mild intensity throughout the washout phase but fades minimally is also classified as grade 3.

The TIMI Coronary Grade Flow is an effective and well-studied grading system of coronary reperfusion on an angiogram. Achieving earlier TIMI grade 3 flow has been correlated with improved survival in both reperfusions with thrombolysis or primary percutaneous coronary intervention (PCI). Additionally, combining TIMI grade flow and TMP can stratify patients at very low risk and high risk for mortality post-STEMI. Proven a useful tool in patients with acute MI, the TIMI grade flow is used routinely.[9][10]

Nursing, Allied Health, and Interprofessional Team Interventions

Since the initial TIMI 1 study, the TIMI flow grading system has been used globally to measure epicardial flow and is considered the “gold standard” model compared to other modalities. It has been studied to show the predictability of clinical outcomes. The global utilization of streptokinase and tissue plasminogen activator for occluded coronary arteries (GUSTO) studied TIMI grade flows and 30-day mortality. The original investigators analyzed data from the GUSTO trial and noted “a lack of patency at 90 minutes (TIMI grade 0 or 1) was associated with mortality of 8.9 percent, and patency (TIMI grade 2 or 3) with mortality of 5.7 percent (P = 0.04). The mortality rate among patients with TIMI grade 2 flow was 7.4 percent, and the rate among those with TIMI grade 3 flow was 4.4 percent (P = 0.08). The difference between the mortality rate associated with grade 3 and the rate associated with grade 0 or 1 was significant (P = 0.009).”

Additionally, patients with TIMI 3 before angioplasty are less likely to develop left ventricular complications and have improved survival. Other examples of clinical significance include a demonstration of increased mortality risk in a patient with low TIMI grade flow (0-2) post-PCI for STEMI among patients with cardiogenic shock, compared to normal post-PCI TIMI grade flow.