Quantitative Assessment of Myocardial Perfusion Using Time-Density Curve Analysis After Elective Percutaneous Coronary Intervention

Abstract: The aim of this study was to assess myocardial blush (MB) using a novel software algorithm that quantifies time-density curves (TDC) after percutaneous coronary intervention (PCI). Methods. Thirty-two patients referred for elective PCI were enrolled. TDC curves were generated and mean maximal myocardial contrast density (Dmax) was calculated from 5 regions of interest in the PCI territory. Dmax was normalized to contrast injected in the proximal coronary artery (DI). Results. Mean DI significantly increased after PCI in all subjects. Dmax correlated directly with subjective grading of Thrombolysis in Myocardial Infarction (TIMI) myocardial blush (R=0.47; P<.01). In 7 subjects referred for PCI of a chronic total occlusion (CTO), mean DI remained increased after PCI. Mean DI was lower in CTO versus non-CTO subjects; however, fold-improvement was higher after PCI of CTO lesions. Conclusion. Quantifying MB using TDC analysis is feasible and correlates with subjective MB grading. The clinical utility of MB quantitation after PCI requires further study. 

J INVASIVE CARDIOL 2014;26(2):60-63

Key words: chronic total occlusion, myocardial blush, PCI, TIMI flow

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Impaired myocardial perfusion (MP) following percutaneous coronary intervention (PCI) correlates with poor clinical outcomes.^1-3 The traditional Thrombolysis in Myocardial Infarction (TIMI) parameters for assessment of MP include TIMI perfusion grade, TIMI frame count, and TIMI myocardial blush grade; however, these techniques are at best semi-quantitative and do not provide a comprehensive assessment of both epicardial and tissue-level perfusion. A novel software system has recently been designed to quantitatively assess regional cardiac perfusion in the cardiac catheterization laboratory. This program digitally subtracts background structures within the chest to better visualize contrast in the coronary artery and myocardial bed. The program then generates a time-density curve (TDC) of epicardial coronary artery and myocardial contrast density to allow the accurate quantification of global cardiac perfusion. The aim of this study was to assess MP using TDC analysis after elective PCI.

Methods

Patient selection and angiography. Thirty-two consecutive patients without acute coronary syndrome or heart failure referred for elective PCI were enrolled. A control group consisting of 25 consecutive patients who underwent coronary angiography for clinical indications but who did not require PCI was also enrolled. This study was approved by the Institutional Review Board.  

For each patient, pre- and post-PCI cineangiography of the culprit artery with breath-hold was performed at 30 frames/s using the GE Healthcare Innova 2100 Cardiovascular Imaging system. All angiograms were obtained using a 6 Fr catheter. The angiographic sequence was recorded until there was visual confirmation of washout phase from the myocardium.Standardized projections were right anterior oblique 30°/cranial 30° for the left anterior descending (LAD) artery, right anterior oblique 40°/caudal 30° for the left circumflex (LCX) artery, and left anterior oblique 30°/cranial 15° for the right coronary artery (RCA).

TDC analysis. Next, the digital angiographic sequences were analyzed offline and TDC curves were generated for quantitative assessment of MP using proprietary software (GE Healthcare). The detailed process of TDC curve generation has been previously described.⁴ Once the digitally subtracted angiography images were obtained showing only those heart regions where there was blood flow (ie, coronary arteries, arterioles, myocardial capillaries, and veins), five regions of interest were proscribed in each of the coronary artery territories. The density of contrast in each myocardial region was calculated, and from these raw data, the TDC was generated.  The average of the 5 regions in each coronary artery territory was used for the analysis in each patient and at each time point (ie, before and after PCI). 

Figure 1 demonstrates a simulated TDC curve with the parameters measured. Dmax (myocardium) normalized to maximal contrast density in the proximal coronary artery at the time of injection (DI) served as a quantitative measure of myocardial blush. Expressed as a percentage, the DI x 100 gave the density differential (DD), which took into account the volume and rate of contrast injection. In addition to DI, the time required for contrast to transit the vasculature was calculated. The difference in Tmax (the time at which Dmax occurs) between the proximal artery and the myocardial bed was described as transit time (TT). Finally, the ratio of DD to TT, or DTR, was calculated as a single numerical figure to describe myocardial perfusion, accounting for injection rate and volume as well as the TT of contrast through the vessel into the myocardium.

Statistical analysis. Data are presented as means ± standard error of the mean (SEM) unless otherwise stated. Interventions were classified into 2 groups: chronic total occlusion (CTO; n = 7) or non-CTO (n = 25). Comparisons of TDC parameters between each time point (ie, before and after PCI) were performed using the Student’s t-test. Non-parametric testing using the Spearman correlation coefficient was used for comparing non-CTO versus CTO PCI data as well. TIMI parameters of myocardial perfusion for all cases (myocardial perfusion grade and myocardial blush grade) were graded by three blinded reviewers. All TDC-derived parameters were correlated with TIMI parameters using Spearman’s correlation coefficient. A P-value <.05 was considered significant for all analyses.

Results

Patients. The baseline patient characteristics for the non-CTO, CTO, and control groups are listed in Table 1. There were no significant differences between the non-CTO and CTO patients in terms of demographics, comorbidities, and clinical parameters. There were also no differences between either the non-CTO or CTO groups and the control group in any category of comparison. 

Myocardial blush. The baseline mean DI was significantly lower in the total PCI cohort compared to controls (0.28 vs 0.52, respectively, P<.01, Figure 2). The baseline DI was significantly higher in the non-CTO versus CTO PCI groups (0.43 vs 0.13, respectively; P<.01). The mean DI for all 32 subjects in the PCI group significantly increased following PCI (0.28 before PCI vs 0.43 after PCI; P<.01). A significant rise in pre- to post-PCI DI was also noted for both the non-CTO group (0.43 vs 0.56, respectively; P<.01) and the CTO group (0.13 vs 0.30, respectively; P<.01). While the mean DI at baseline was lower in the CTO vs non-CTO subjects (0.13 vs 0.43, respectively; P<.01), the degree of improvement in mean DI was higher after revascularization of CTO compared to non-CTO lesions (2.3-fold vs 1.3-fold, respectively; P<.01) (Figure 3). Dmax measured both before and after non-CTO PCI correlated directly with before and after CTO PCI (R=0.35, P<.001). Dmax correlated directly with subjective grading of TIMI myocardial blush (R=0.47, P<.001).

Discussion

In this study, we utilized a novel software algorithm to quantitatively assess myocardial perfusion before and after elective PCI. We found that DI increased significantly after PCI, as well as in both the CTO and non-CTO subgroups. The CTO sub-group also received the most benefit after revascularization, with a significantly larger rise in DI compared to the non-CTO subgroup after PCI. TIMI myocardial blush grade correlated well with the program’s measurement of maximal density, making Dmax a sensitive indicator of MB.  

MB, a graded assessment of myocardial performance, has traditionally been visually inspected during angiography as contrast density travels through the coronary vessels and perfuses the microvasculature and myocardium. It has been subjectively measured with TIMI perfusion grade, TIMI myocardial blush grade, and TIMI frame count. Not only have these TIMI parameters been used to estimate short-term 30-day outcomes after MI, but some studies have shown them to be predictors of long-term outcomes as well, making MB an important prognostic indicator of survival.⁵ Several studies have used quantitative techniques to grade MB after STEMI, concluding that there was an association between their respective quantitative indicators and myocardial reperfusion and recovery.^6,7 One study using the same novel software on a porcine model of MI showed good correlation between TDC-derived parameters of MB and traditional TIMI myocardial perfusion grade.⁴

In this study, the CTO subgroup had a 2.3-fold increase in DI after intervention. However, the clinical utility of PCI in patients with CTOs has been controversial. These patients have a highly vascularized collateral network distal to the occlusion, which may be a risk factor for procedural failure.⁸ Collateral flow may decrease after CTO revascularization; however, this does not necessarily correlate with improved myocardial perfusion, most likely because of microvascular injury or time-dependent changes in the area of ischemic myocardium.⁹ The Occluded Artery Trial (OAT), which enrolled patients with a total occlusion after a recent MI and randomized them to treatment groups of PCI with medical therapy or medical therapy alone, showed no difference in outcomes between the two cohorts.¹⁰ However, there have been several other studies showing a survival benefit from revascularization of CTOs.^11-13 One study examining the 10-year survival between CTO vs non-CTO patient populations undergoing PCI described a similar survival rate between the two groups, showing that patients with occlusive coronary disease can benefit from successful revascularization.¹⁴ In the present study, we identified a significant increase in myocardial perfusion after CTO revascularization using this novel software algorithm. Future studies validating the clinical utility of calculating DI after both CTO and non-CTO intervention are required.

Study limitations. Limitations to the present proof-of-concept study include a small sample size and lack of direct measurements of myocardial perfusion using invasive methods or non-invasive imaging. The small number of CTO patients remains a limitation and should be investigated in future studies to corroborate the validity of our conclusions.

Conclusion

In conclusion, we report that TDC analysis is a feasible method to quantify myocardial perfusion after elective PCI as opposed to subjective grading using the TIMI blush score alone. Future studies are warranted to examine the prognostic value of quantitatively assessing MB in the catheterization lab. 

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