Infarct evolution in man studied in patients with first-time coronary occlusion in comparison to different species - implications for assessment of myocardial salvage

Abstract

Background: The time course of infarct evolution, i.e. how fast myocardial infarction (MI) develops during coronary artery occlusion, is well known for several species, whereas no direct evidence exists on the evolution of MI size normalized to myocardium at risk (MaR) in man. Despite the lack of direct evidence, current literature often refers to the "golden hour" as the time during which myocardial salvage can be accomplished by reperfusion therapy. Therefore, the aim of the present study was to investigate how duration of myocardial ischemia affects infarct evolution in man in relation to previous animal data. Consecutive patients with clinical signs of acute myocardial ischemia were screened and considered for enrollment. Particular care was taken to assure uniformity of the patients enrolled with regard to old MI, success of revascularization, collateral flow, release of biochemical markers prior to intervention etc. Sixteen patients were ultimately included in the study. Myocardium at risk was assessed acutely by acute myocardial perfusion single photon emission computed tomography (MPS) and by T2 imaging (T2-STIR) cardiovascular magnetic resonance (CMR) after one week in 10 of the 16 patients. Infarct size was measured by late gadolinium enhancement (LGE) at one week.

Results: The time to reach 50% MI of the MaR (T50) was significantly shorter in pigs (37 min), rats (41 min) and dogs (181 min) compared to humans (288 min). There was no significant difference in T50 when using MPS compared to T2-STIR (p = 0.53) for assessment of MaR (288 +/- 23 min vs 310 +/- 22 min, T50 +/- standard error). The transmural extent of MI increased progressively as the duration of ischemia increased (R2 = 0.56, p < 0.001).

Conclusion: This is the first study to provide direct evidence of the time course of acute myocardial infarct evolution in relation to MaR in man with first-time MI. Infarct evolution in man is significantly slower than in pigs, rats and dogs. Furthermore, infarct evolution assessments in man are similar when using MPS acutely and T2-STIR one week later for determination of MaR, which significantly facilitates future clinical trials of cardioprotective therapies in acute coronary syndrome by the use of CMR.

Figure 1

Myocardial infarct size in relation to myocardium at risk with respect to duration of ischemia in different species. A linear and logarithmic time scale is presented in the left and right panel, respectively. A: Data from previous studies in pigs (black circle = Fujiwara et al [9], white circle = Näslund et al [6]. B: Data from previous studies in rats (black circle = Hale et al [8], white circle Arheden et al [11]). C: Data from previous studies in dogs (white triangle = Reimer et al [3], black circle = Kloner et al [7], upward black triangle = Fujiwara et al [9], downward black triangle = Reimer et al [10]). D: Human data from the present study. The dashed lines represent the 95% confidence intervals. MaR = myocardium at risk; MI = myocardial infarction.

Figure 2

Infarct progression for different species. Comparison of the infarct progression slope (A) and the time to reach 50% MI of the MaR (B) for the different species. There was a significantly slower infarct evolution in man compared to pigs, rats and dogs. Consequently, the time to reach 50% MI of the MaR was longer for humans compared to pigs, rats and dogs. *** = p < 0.001; ** = p < 0.01; MaR = myocardium at risk; MI = myocardial infarction.

Figure 3

Infarct evolution in man: MPS vs T2-STIR for myocardium at risk. Infarct evolution when using (A) MPS and (B) T2-STIR for assessment of MaR. The dashed lines represent the 95% confidence intervals in A and B. There was no significant difference between MPS and T2-STIR for assessing infarct evolution (C). MaR = myocardium at risk; MI = myocardial infarction; MPS = myocardial perfusion SPECT; T2-STIR = T2-weighted double inversion blood suppressed turbo spin echo CMR sequence.

Figure 4

Infarct transmurality in relation to duration of ischemia in man. As duration of ischemia increased the transmural extent of MI increased progressively. MI = myocardial infarction.

Figure 5

Representative cases. Fusion of polar plots from MPS acquired acutely and LGE images acquired one week after the acute MI in two patients subjected to ischemia for 110 and 190 minutes, respectively. The MPS polar plots indicate MaR (black) in the otherwise well perfused myocardium (yellow). The center of the polar plot represents the left ventricular apex and the periphery represents the basal parts of the left ventricle. Final MI size by LGE is shown in white, where brightness indicates MI transmurality from 0% (black) to 100% (white). LGE = late gadolinium enhancement; LV = left ventricle; MaR = myocardium at risk.