Myocardial Perfusion Grade (MPG) After Late Infarct Artery Recanalization is Associated With Global and Regional LV Function at One Year; Analysis From the Total Occlusion Study of Canada-2

Abstract

Background

Whether myocardial perfusion grade (MPG) following late recanalization of infarct-related arteries (IRA) predicts left ventricular (LV) function recovery beyond the acute phase of myocardial infarction (MI) is unknown.

Methods and Results

The Total Occlusion Study of Canada-2 (TOSCA-2) enrolled stable patients with persistently occluded IRA beyond 24 h and up to 28 days post-MI. We studied the relationship between the initial MPG and changes in LV function and volume, and the change in MPG from immediate post-PCI to one year in 139 PCI patients with TIMI 3 epicardial flow post PCI and with paired values, grouped into impaired or good MPG groups (MPG 0/1 or MPG 2/3). MPG 0/1 patients were more likely to have received thrombolytic therapy and to have a LAD IRA. They had lower blood pressure and LV ejection fraction (LVEF), and a higher heart rate and systolic sphericity index at baseline. Changes in the MPG 0/1 and MPG 2/3 groups from baseline to 1 year were: LVEF 3.3±9.0 and 4.8±8.9 percent (p=0.42), LV end-systolic volume index (LVESVI) -1.1±9.2 and -4.7±12.3 ml/m² (p=0.25), LV end-diastolic volume index (LVEDVI) 0.08±19.1 and -2.4±22.2 ml/m² (p=0.67), and standard deviations /chord for infarct zone wall motion index (WMI)) 0.38±0.70 and 0.84±1.11 (p=0.01). By covariate-adjusted analysis, post-PCI MPG 0/1 predicted lower WMI (p<0.001), lower LVEF (p<0.001) and higher LVESVI (p<0.01), but not LVEDVI at one year. Of the MPG 0/1 patients, 60% were MPG 2 or 3 at one year.

Conclusions

Preserved MPG is present in a high proportion of patients following late PCI of occluded IRAs post-MI. Poor MPG post-PCI frequently improves MPG over 1 year. MPG graded after IRA recanalization undertaken days to weeks post MI is associated with LV recovery indicating that MPG determined in the subacute post-MI period remains a marker of viability.

Timely recanalization and sustained patency of the infarct related artery (IRA) are major determinants of left ventricular (LV) function and survival after acute myocardial infarction (MI). Patients with normal epicardial flow in the IRA (Thrombolysis in Myocardial Infarction [TIMI] grade 3) but reduced tissue level perfusion as quantified by TIMI Myocardial Perfusion Grade (MPG) immediately following acute reperfusion with fibrinolysis, primary or rescue PCI¹ have longer ischemic times, larger infarcts, worse global and regional LV systolic function, and increased mortality^{2, 3}. These observations suggest that MPG marks microvascular integrity and is thereby a surrogate for myocardial viability in the acute phase of MI^4-7.

In contrast to the extensively documented benefit of early recanalization, routine late recanalization (beyond 24 hours) after symptom onset is not well supported by evidence^{8, 9}, and is not guideline-recommended. Until recently late PCI for persistent occlusion has generally been performed on the basis of the late open artery hypothesis¹⁰. The extent to which effective microvascular reperfusion can be achieved by PCI performed after the acute phase, and whether it is followed by regional or global functional recovery of the left ventricle is unknown. The Occluded Artery Trial (OAT)⁹ was a multi-center randomized controlled trial that evaluated the benefit of PCI in addition to optimal medical therapy compared to optimal medical therapy alone in patients beyond the first 24 hours and up to 28 days after MI onset. The Total Occlusion Study of Canada (TOSCA)-2 was a NHLBI-funded angiographic ancillary study of OAT with co-primary end-points of infarct-related artery patency at 1 year and change in LVEF from baseline to 1 year.⁸ Paired coronary and LV angiograms were obtained at baseline and 1 year post-PCI (n=332), providing a unique opportunity to evaluate the association between myocardial perfusion grade (MPG) at baseline (following successful PCI) and global and regional functional recovery at one year follow-up, and to examine the stability of perfusion grade over time.

Methods

Study population

The primary results of TOSCA-2⁸ as well as the study design¹¹ and results⁹ of the parent OAT have been published. Inclusion criteria for TOSCA-2 and OAT included a documented index MI and an occluded infarct-related artery (TIMI Flow Grade 0 or 1) in addition to one of two high-risk criteria – proximal occlusion or LVEF less than 50%. Important exclusion criteria included a clinical indication for revascularization (significant angina, severe inducible ischemia, left main or triple vessel disease), serum creatinine >2.5 mg/dl, severe valvular disease, New York Heart Association Class III or IV heart failure or cardiogenic shock at the time of screening. Inclusion criteria for the MPG analysis included OAT treatment assignment to the PCI group with subsequent successful PCI of IRA with post-PCI antegrade TIMI 3 flow. Finally, baseline, post-PCI and 1-year follow-up coronary angiograms suitable for MPG analysis and analyzable LV angiograms were also required.

Data collection

Baseline characteristics were recorded from the time of index MI to the time of randomization. Qualifying coronary and LV angiograms performed after the first 24 hours and up to 28 days post-MI, as well as post-PCI and follow-up angiograms performed after 1 year were submitted for quantitative analysis performed in a dedicated core angiographic laboratory. LV volumes, LVEF, regional wall motion and sphericity index were calculated as described previously^12-14.

PCI

Protocol PCI of the IRA with routine stenting was performed within 24 hours of randomization. All patients received aspirin and either ticlopidine or clopidogrel beginning the day of the procedure or earlier. Anticoagulation with heparin during PCI to a target Activated Clotting Time of ≥250 seconds was recommended. Use of glycoprotein IIb/IIIa inhibitors was encouraged.

Myocardial Perfusion Grading

The MPG substudy was prospectively planned and participating centers were instructed with respect to technique for obtaining immediate post-PCI and one year follow-up angiograms optimized for MPG analysis, generally requiring a longer cine-angiographic recording focusing on the myocardial segment likely to demonstrate blush. MPG was graded semi-quantitatively by two independent core lab readers (VJ, TS) trained to use standard TIMI MPG criteria¹ and blinded to clinical data and timing, and sequence of angiography. In case of discrepancies, angiograms were re-read independently by both readers and any remaining discrepancies were resolved by a third reader (GBJM). Post-PCI and follow-up angiograms were also evaluated for residual thrombus and evidence of distal embolization. The present analysis was limited to patients with post-PCI TIMI Flow Grade 3 since it is technically difficult to grade myocardial blush when the epicardial vessel is poorly opacified and, moreover, abnormalities of MPG might no longer reflect microvascular function if flow were restricted proximally. We have recently published a reproducibility study including the TIMI MPG method in an angiographic core laboratory where we found a high degree of inter-observer reproducibility when MPG was dichotomized to 0 or 1 vs. 2 or 3¹⁵. Due to the relatively small number of patients in this study and the inherent difficulties in MPG grading we therefore prospectively defined grouping of MPG to 0 or 1 (MPG 0/1) versus 2 or 3 (MPG 2/3).

Statistical analysis

Categorical variables are expressed as frequencies and percentages and continuous variables as means and standard deviations. Categorical variables were compared using Chi -square test or alternatively, Fisher’s exact test if expected frequency for any cell in a 2×2 table was <5. Wilcoxon Two-Sample test was used to compare time intervals from index MI to baseline angiography, randomization and PCI. Independent sample t-test was used to compare other continuous variables that were normally distributed. Within group changes over time were compared using a paired t-test of the difference and between group differences were compared with two sample t-tests. The pre-specified level of significance for all secondary analyses of OAT was p<0.01, while p≥0.01 and <0.05 was considered to indicate a trend toward statistical significance.

Effects of impaired post PCI MPG (MPG 0/1) on one year ejection fraction, wall motion, LV end-systolic volume index (LVESVI) and LV end-diastolic volume index (LVEDVI) were examined in an unadjusted as well as covariate adjusted linear regression model. All baseline covariates that were tested for are listed in Table 1 in the main OAT publication⁹. Adjustments were made for other baseline covariates with p < 0.05 on multiple linear regression using backward elimination. WMI was adjusted for baseline WMI, days to randomization, BMI and new Q waves. LVEF was adjusted for baseline LVEF, heart rate, BMI and new Q waves. LVESVI was adjusted for baseline LVESVI, no family history, NYHA > 1 at presentation and LAD as the IRA.

Table 1.

Baseline clinical characteristics by post-PCI MPG

Characteristic	Post-PCI MPG 0/1 N= 33	Post-PCI MPG 2/3 N= 124	p value
Male, %	78.8	85.5	0.350
Age yrs, mean (SD)	54.6 (9.2)	57.4 (10.5)	0.174
Body mass index	28.6±4.5	27.6±4.1	0.21
Diabetes, %	24.2	16.9	0.336
Hypertension, %	48.5	50.8	0.813
Hyperlipidemia, %	48.5	58.9	0.285
Family history of CAD, %	42.4	48.4	0.542
Current smoker, %	42.4	31.5	0.236
Prior angina, %	12.1	21.8	0.216
Prior MI, %	6.1	13.7	0.368
Interval from MI to baseline angiogram (days), median (IQR)	5 (4, 8)	5 (3, 9)	0.566
Interval from MI to randomization (days), median (IQR)	9 (5, 17)	10 (6, 20)	0.512
Interval from MI to PCI (days), median (IQR)	10 (5, 18)	10 (7, 20)	0.507
Interval from baseline angiogram to PCI (days), median (IQR)	3 (0, 9)	2 (0, 12)	0.939
Heart rate beats/min, mean (SD)	74.9 (12.1)	67.4 (10.9)	0.001
Systolic blood pressure mmHg, mean (SD)	108.4 (16.5)	119.3 (15.1)	0.0004
Diastolic blood pressure mmHg, mean (SD)	66.9 (9.7)	72.1 (10.8)	0.014
Fibrinolytic therapy during first 24 hr of index MI (%)	45.4	16.9	<0.001
ST elevation >0.1mV, %	72.7	59.8	0.175
ST depression > 0.1 mV, %	36.4	30.3	0.508
New Q waves, %	63.4	65.3	0.860
Maximum pre-PCI Total CK divided by ULN, mean (SD)	10.1 (6.2) (n=27)	7.1 (7.3) (n=104)	0.048
Maximum pre-PCI CK MB divided by ULN, mean (SD)	23.4 (26.6)	11.8 (14.3)	0.123
Maximum pre-PCI TNI divided by ULN, mean (SD)	172.4 (152.0)	271.4 (713.6)	0.253
Maximum pre-PCI TNT divided by ULN, mean (SD)	229.5 (215.9)	50.6 (50.3)	0.138
Killip Class > 1 during index MI,%	9.1	10.5	0.999
NYHA Class > 1 at randomization,%	9.1	6.4	0.700

Abbreviations PCI: percutaneous coronary intervention, MPG: Myocardial Perfusion Grade, SD: standard deviation, CAD: coronary artery disease, MI: myocardial infarction, IQR (interquartile range), ULN: upper limit of the local laboratory normal, CK: creatine kinase, TNI: troponin I, TNT: troponin T

Results

Distribution of MPG

Of the 381 patients enrolled in TOSCA-2, 195 were assigned to PCI, and of these 186 had angiograms potentially suitable for baseline MPG analysis. The nine angiograms that were excluded had too short cine-angiographic recordings for analysis. The distribution of post-PCI TIMI Flow Grade in these 186 patients was: Grade 0 in 12 (6.5%), Grade 1 in 6 (3.2%), Grade 2 in 11 (5.9%) and Grade 3 in 157 (84.4%) patients. MPG, evaluated in all 157 patients with TIMI Flow Grade 3, was distributed as follows: MPG 0 in 25 (15.9%), MPG 1 in 8 (5.1%), MPG 2 in 77 (49.0%) and MPG 3 in 47 (29.9%). Baseline clinical characteristics of the MPG 0/1 and MPG 2/3 groups are provided in Table 1, angiographic and procedural characteristics in Table 2. Of these 157 evaluable patients, 142 also had MPG and global and regional left ventricular functional parameters suitable for analysis at 1-year follow up. Paired analyses were available for 139 patients (post-PCI and 1 year).

Table 2.

Angiographic and procedural characteristics by post-PCI MPG

	Post-PCI MPG 0/1 N = 33	Post-PCI MPG 2/3 N = 124	p value
Pre-PCI coronary angiography
IRA – LAD, %	54.6	21.8	<0.001
IRA – Circumflex, %	21.2	9.7
IRA – RCA, %	24.2	68.5
IRA TIMI Flow Grade 0 to 1, %	100.0	98.4	1.000
Collaterals present, %	72.3	95.1	<0.001
Single vessel disease, %	87.9	81.4	0.385
Pre-PCI left ventricular angiography
Infarct Segment Regional WMI SD/Chord, mean (SD)	-3.2 (0.7)	-2.9 (1.0)	0.177
LVEF, mean (SD)	42.6 (11.6)	50.6 (8.7)	<0.001
LVESVI, mean (SD)	39.8 (20.1)	31.3 (14.3)	0.08
LVEDVI, mean (SD)	69.7 (27.3)	63.6 (24.7)	0.34
Diastolic Sphericity Index, mean (SD)	31.0 (5.3)	30.8 (6.4)	0.862
Systolic Sphericity Index, mean (SD)	25.3 (6.1)	22.9 (5.5)	0.035
Mitral Regurgitation present, %	28.1	35.8	0.414
Procedural characteristics and post-PCI angiography
Residual thrombus (%)	9.1	2.4	0.108
Distal embolization n (%)	3.0	8.9	0.462
Post-PCI residual % diameter stenosis, mean, (SD)	29.8 (17.6)	27.8 (14.3)	0.507
Post-PCI Minimal Luminal Diameter mm, mean, (SD)	2.2 (0.6)	2.3 (0.5)	0.097
Glycoprotein IIb/IIIa inhibitors used (%)	90.9	83.1	0.27
Stent implanted, %	100.0	99.2	1.000

Abbreviations IRA: infarct-related artery, LAD: left anterior descending coronary artery, RCA: right coronary artery, TIMI: Thrombolysis in Myocardial Infarction, WMI: wall motion index, LVEF: left ventricular ejection fraction, LVESVI: left ventricular end-systolic volume index, LVEDVI: left ventricular end-diastolic volume index, other abbreviations as in Table 1.

Univariate correlates of impaired MPG post PCI

At baseline, patients with MPG 0/1 had evidence of larger infarcts, lower systolic blood pressure and LVEF, and a trend to a larger LVESVI and higher peak CK, compared to patients with MPG 2/3. They were also more likely to have an occluded LAD and to have been treated with fibrinolytic therapy for the index MI, and were less likely to have angiographically visible collaterals. Glycoprotein IIb/IIIa inhibitors were used in a majority of cases with no difference between groups. (Tables 1 and 2). These baseline findings are similar to those reported for the larger cohort of 261 OAT ancillary study patients in whom baseline MPG was measured¹⁶.

Optimal Medical Treatment

Both MPG groups had high rates of optimal medical therapy during hospital stay, at discharge and at one year follow-up, with no differences observed between the groups. (Table 3)

Table 3.

Utilization of Medical Therapies at discharge and at 1 year (by MPG)

	Discharge
	MPG 0/1 (N=30)		MPG 2/3 (N=109)		p-value
	N	%	N	%
Aspirin	29	96.7	108	99.1	0.39
Thienopyridines (clopidogrel or ticlopidine)	30	100.0	108	99.1	1.00
Aspirin or thienopyridine	30	100.0	109	100.0	NA
Aspirin plus thienopyridine	29	96.7	107	98.2	0.52
Warfarin	5	16.7	4	3.7	0.02
One or more of ASA, warfarin, thienopyridine	30	100.0	109	100.0	NA
Two or more of ASA, warfarin, thienopyridine	30	100.0	107	98.2	1.00
B-blocker	28	93.3	97	89.0	0.73
ACE inhibitor or ARB	29	96.7	94	86.2	0.19
Spironolactone	4	13.3	2	1.8	0.02
Lipid lowering agent	28	93.3	92	84.4	0.37
	1 year
	1 Year MPG 0 or 1 (N=29)		1 Year MPG 2 or 3 (N=106)		p-value
	N	%	N	%
Aspirin	28	96.6	100	94.3	1.00
Thienopyridine (clopidogrel)*	9	31.0	29	27.4	0.70
Aspirin or thienopyridine	28	96.6	103	97.2	1.00
Aspirin plus thienopyridine	9	31.0	26	24.5	0.48
B-blocker	28	96.6	89	84.0	0.12
ACE inhibitor or ARB	28	96.6	92	86.8	0.19
Spironolactone	4	13.8	6	5.7	0.22
Lipid lowering agent	28	96.6	93	87.7	0.30

Changes in LV size and function over one year

As a group, patients with MPG 2/3 showed significant improvement at follow-up in measures of global contractility, including LVEF and LVESVI. In contrast, those with MPG 0/1 showed no improvement. The more demanding between-group comparison testing for differential effects of post-PCI MPG upon these LV parameters was not, however, significant (Figure 1A, 1B). Regional contractility of the infarct zone as expressed by the wall motion score improved in both MPG groups at follow-up, but the degree of wall motion improvement observed in the MPG 2/3 group was significantly greater than that observed in the MPG 0/1 group (Figure 1D). No significant change or difference was noted within or between MPG groups for LVEDVI (Figure 1C). We also observed significantly lower Systolic Sphericity Index at one year in the MPG 2/3 versus 0/1 groups (0.206 vs. 0.240, p=0.008).

Figure 1.

Comparison of baseline (post PCI) and follow-up at 1 year of (A) LVEF. (B) LVESVI (End Systolic index), (C) LVEDVI and (D) Target region wall motion (SD / chord) between groups (MPG 0/1 vs. MPG 2/3). Paired data. Values are given for change within group and p-values for within group and between groups comparison.

Changes in MPG over one year

Of the 109 MPG 2/3 group patients, 18 (17%) had MPG 0 or 1 at one year (Table 4). Binary restenosis in the IRA was observed in 16 of these patients (88.9%) and in 27 of 91 patients (29.7%) in whom MPG remained 2 or 3 (p<0.0001). Mean diameter stenosis was 82.5±22.8 vs. 43.9±20.4% (p<0.0001) in these two groups. Of the post-PCI MPG 0/1 group, 60% had MPG 2 or 3 at one year. Amongst the 30 MPG 0/1 patients with angiographic follow-up, restenosis was observed in 9 of the 18 (50%) with MPG 2 or 3 at one year, and 3 of 12 (25%) with persistent MPG 0 or 1 (p=0.17).

Table 4.

Changes in MPG over one year

One-Year MPG
Post-PCI MPG	MPG 0 or 1	MPG 2 or 3	Total
MPG 0/1	12 (40%)	18 (60%)	30 (22%)
MPG 2/3	18 (17%)	91 (83%)	109 (78%)
Total	30 (22%)	109 (78%)	139 (100%)

P value for changes is 0.006

Independent correlates of LV size and function at one year (by post PCI MPG)

On multivariable analysis (Table 5) post PCI MPG 0/1 predicted lower WMI (p=0.0002) and LVEF (p=0.0008), and a higher LVESVI (p=0.0056) at 1 year.

Table 5.

Effects of post-PCI MPG 0/1 vs. post-PCI MPG 2/3 on LV outcome measures at 1 year

Variable	Unadjusted
	Parameter estimate	SEM	T value	P value
Infarct Segment Regional WMI (n=118)	-0.67	0.23	-2.90	0.0045
LVEF (n=126)	-8.86	1.92	-4.60	<0.0001
LVESVI (n=76)	7.23	3.14	2.30	0.023
LVEDVI (n=76)	4.66	5.34	0.87	0.39
	Covariate adjusted
Infarct Segment Regional WMI	-0.71	0.18	-3.89	0.0002
LVEF	-5.75	1.67	-3.43	0.0008
LVESVI	7.16	2.50	2.86	0.0056
LVEDVI	4.49	4.81	0.93	0.35

WMI adjusted for baseline WMI, days to randomization, BMI and new Q waves.

LVEF adjusted for baseline EF%, heart rate, BMI and new Q waves.

LVESVI adjusted for baseline LVESVI, no family history, NYHA >I, and LAD culprit.

LVEDVI adjusted for baseline LVEDVI, baseline LVEF, and LAD culprit

Discussion

This study addresses the ability of MPG to discriminate amongst patients with successful PCI of occluded infarct arteries, those who will have favorable changes in LV function from those who will not. To our knowledge this is the first study addressing the association between MPG and global and regional recovery of LV function following late recanalization of the IRA after MI, and also the first study to describe MPG at 1-year follow-up.

The study population was uniformly selected, and uniquely suited to test MPG as a predictor of LV recovery post-MI. OAT enrolled stable patients with occluded IRAs who underwent recanalization with PCI/stent. We selected only patients with normal epicardial flow immediately post PCI, after a median occlusion time of 10 days. Notably 79% of our cohort demonstrated MPG 2/3. Extending the results of studies examining acute reperfusion cohorts, preserved MPG was significantly associated with better indices of LV systolic function at 1 year (Figure 1). We also observed that MPG improved significantly from post PCI to follow-up at one year.

Distribution of MPG

Our results are consistent with a large study of early recanalization by primary PCI with good epicardial and microvascular flow in 1190 of 1548 patients (76.9%)¹⁷. In a recent publication on thrombus aspiration in the setting of acute MI, 75 to 82% of patients had myocardial blush grade 2 or 3¹⁸. These two studies both used myocardial blush grade¹⁷ which, while employing somewhat different criteria, is angiographically and conceptually similar to the MPG system we used. The results are comparable to the 79% prevalence following successful late recanalization after the first 24 hours and up to 28 days post MI in the present study.

Several factors may be responsible for the high rates of preserved MPG following late PCI in the present study. We selected only patients with TIMI 3 flow post-PCI, as explained in the methods section. Stents were implanted in nearly all patients (99.4%) and angiographic evidence of residual thrombus and distal embolization was seen only in a very small number of patients. Finally, the myocardial edema and microvascular plugging by aggregates of leukocytes and platelets, typical of AMI may have begun to resolve in many of our patients. Rochitte and colleagues¹⁹ showed that the extent of microvascular obstruction increases over the first 48 hours after experimental acute myocardial infarction and reperfusion in canines. The same group reported that the peak extent of microvascular obstruction occurs two days after reperfusion and is unchanged at nine days²⁰. Hozumi and co-workers²¹, using coronary Doppler ultrasound, reported short deceleration time of diastolic flow velocity (DDT), a measure of microvascular resistance, one day after IRA recanalization, indicating poor runoff in the microcirculation. Interestingly they found significantly longer DDT, indicating lower microvascular resistance, one and two weeks after acute IRA recanalization, both in a group with viable and a group with non-viable myocardium in the region of interest. In both groups the DDT normalized by two weeks after recanalization. The authors postulated that after the first two days following reperfusion there is a gradual recanalization of the occluded microvessels, causing a progressive decrease in coronary resistance, even in areas without viable myocardium. In support of this we observed an increase in the number of patients showing MPG 2 or 3 at 1 year compared to post-PCI. In light of these data it seems clear that poor blush can improve, indicating it does not always imply irreversible necrosis of the microvasculature even if the subtended myocardium is substantially infarcted. The change in MPG from good to worse is associated with severe restenosis in the IRA, suggesting that parts of the microcirculation in areas with scar tissue may occlude spontaneously over time in the presence of severe restenosis, even if the epicardial artery remains patent with TIMI 3 flow. Alternatively, assessment of MPG in the presence of a severe upstream stenosis, particularly in a previously infarcted region, may be unreliable.

Functional recovery in the context of TOSCA-2 results

In TOSCA-2, significant improvement in LVEF was observed at 1 year in both medically-treated, as well as PCI patients of about the same magnitude as in the MPG 2/3 group in our substudy (4.8±8.9%)⁸. The MPG 0/1 subgroup likely had more densely infarcted myocardium, and microvascular derangement as evidenced by the significantly lower LVEF and larger volumes just a few days post MI. As already stated, however, it does not appear that, if poor myocardial perfusion represents a larger infarct and microvascular derangement, that this derangement is entirely irreversible. In addition, improvement in LVEF appeared to be attenuated in the MPG 0/1 subgroup but was not significantly different from the MPG 2/3 subgroup. Also, the target regional wall motion score significantly increased in the MPG 0/1 group, which means there is some viability retained even with poor blush immediately post-PCI.

Rather, early poor perfusion may represent a larger extent of injury causing microvascular dysfunction and early ventricular dilation that has potential for recovery over time. This is further supported by the OAT nuclear ancillary study²² in which improvement in LVEF over 1 year was predicted by baseline infarct zone viability.

Infarct size and MPG

Patients with baseline clinical and angiographic features of larger infarct size subsequently exhibited impaired MPG following PCI in agreement with previous studies suggesting that infarct size is closely related to microvascular obstruction, despite restoration of epicardial patency^23,24. Infarct size was shown to be a major determinant of reflow following release of coronary occlusion in an experimental model of coronary occlusion and recanalization²⁴. We found fewer collaterals, significantly more LAD occlusions and a greater likelihood of unsuccessful fibrinolytic therapy in the MPG 0/1 group. These findings are similar to those reported for the larger cohort of 261 OAT ancillary study patients in whom baseline MPG was measured¹⁶ and in correspondence with data published by Kandzari et al.²⁵ from a study of primary percutaneous revascularization in acute myocardial infarction, showing that anterior infarction is associated with greater impairment of LVEF, less frequent collateral flow and diminished reperfusion success as measured by MPG.

We reported in our previous publication¹⁶, that failed fibrinolytic therapy was significantly associated with impaired MPG following late recanalization of occluded IRAs by PCI. The association was no longer significant when adjusted for multiple variables that correlate with infarct size. This suggests that impaired post-PCI MPG in patients with failed fibrinolytic therapy is mainly related to larger infarct size and we may speculate that fibrinolytic therapy is preferentially administered to the more critically ill patients. Thus, the higher frequency of impaired MPG in patients suffering from LAD occlusion may be related to larger infarcts in these patients. Absence of collaterals, noted more often with LAD occlusion, may have further contributed to higher frequency of impaired MPG in this subset.

Limitations

Myocardial perfusion as assessed by contrast angiography is semi quantitative and might be considered a difficult parameter to adjudicate. We have, however, recently published a reproducibility study including the TIMI MPG method in an angiographic core laboratory¹⁵. We found a high degree of inter-observer reproducibility when MPG was dichotomized to 0 or 1 vs. 2 or 3. This is the main reason why we prospectively defined grouping of MPG to 0 or 1 versus 2 or 3. The study population in TOSCA 2 was relevant to examining the benefit of routine late PCI compared to medical therapy alone in patients with occluded infarct-related arteries post-MI and the results cannot be extrapolated to all patients undergoing late PCI after MI. We analyzed MPG only in the subset of this population with antegrade TIMI 3 flow post late IRA recanalization. Follow up coronary angiography may reflect ascertainment bias, with sicker patients not returning. Therefore it is unknown whether the reported findings in a subset of patients extend to the entire cohort.

Conclusion

Preserved MPG is present in the majority of MI survivors with normal epicardial flow following late PCI recanalization of their occluded infarct-related artery. Impaired baseline MPG is associated with unfavorable LV indices while preserved baseline MPG in our cohort is associated with segmental and global LV recovery. This observation extends prior analyses undertaken in acute MI settings and is consistent with favorable MPG marking retained viability within the infarct zone. Finally, those with poor baseline MPG frequently show MPG improvement and significantly, but modestly improved wall motion over 1 year, thus a relative lack of LV functional improvement. These data suggest that microvascular integrity and myocardial viability can be disengaged from one another in the chronic post-MI phase, and warrants further study.

The extent to which effective microvascular perfusion can be achieved by percutaneous coronary intervention (PCI) performed after the acute phase of a myocardial infarction (MI), and whether the magnitude of microvascular perfusion affects left ventriclar recovery (LV) is unknown. The Total Occlusion Study of Canada-2 (TOSCA-2), an ancillary study of the 2166-patient Occluded Artery Trial, enrolled 381 stable patients with persistently occluded infarct-related artery (IRA) days to weeks post-MI to PCI or medical therapy alone. Change in myocardial perfusion grade (MPG) was determined from immediate post-PCI to one year (157 patients) and the relationship between initial MPG and LV function and volume were assessed in 139 patients. Preserved MPG was present in the majority of patients with normal epicardial flow following late PCI recanalization of the IRA. Impaired baseline MPG was associated with unfavourable LV indices while preserved baseline MPG was associated with segmental and global LV recovery. Those with poor baseline MPG frequently showed MPG improvement and significantly, but only modestly improved wall motion over 1 year. Thus, microvascular integrity and myocardial viability can be disengaged from one another in the chronic post-MI phase, but subgroups of stable patients with areas of viable myocardium might benefit from late recanalization. Preserved MPG immediately post-PCI may be associated with LV recovery.