Methods

We retrospectively analyzed 152 lesions in 132 patients with stable angina pectoris who underwent both coronary angiography and FFR for the assessment of myocardial ischemia from January 2011 to March 2016 at Ehime University Graduate School of Medicine. Patients who had angiographically diffuse coronary artery stenosis, significant left main coronary artery disease, in-stent restenosis disease, graft disease, severe systolic dysfunction (left ventricular ejection fraction, ≤40%), or an infarct-related artery were excluded from the present study. The institutional review boards of our hospital approved the retrospective use of patient data.

Diagnostic coronary angiography was performed using 4Fr to 6Fr coronary catheters. Intracoronary isosorbide dinitrate (1.25 mg) was administered before the angiogram and a pressure-monitoring guidewire (Verrata or Prime Wire Prestige PLUS or Prime Wire; Volcano, San Diego, California) was advanced into the distal coronary vessel past and through the lesion. Hyperemia was induced by intravenous administration of adenosine triphosphate (0.16 mg/kg/min), as previously reported. Functional myocardial ischemia was determined as an FFR 0.8 or less, according to previous reports.

QCA analysis was performed by an experienced QCA analyst who was blinded to the FFR results. QCA was performed offline using automated software (CAAS II; Pie Medical Imaging BV). Angiographic views with the least foreshortening and yielding the best depiction of the stenoses were used. Measurements were performed on image sequences adequately filled with contrast and on the lesion of interest. Proximal and distal reference locations were determined manually to cover the entire lesion and to measure the diameter of the normal segment of the vessel ( Figure 1 ). When there were tandem lesions, both lesions were covered manually. The absolute reference diameter, minimum lumen diameter, diameter stenosis, and lesion length were calculated using the contrast-filled angiographic catheter as a scaling device ( Figure 1 ).

Representative demonstration showing TP calculation. (A) QCA was performed offline using automated software. Proximal (P) and distal reference (D) locations were performed manually, to cover the entire lesion. (B) Coronary lumen area and percent diameter stenosis were calculated using both densitometry and lumen edges (% diameter stenosis: 69%, % Area stenosis: 76%). (C) Pressure loss was calculated from the equation: ΔP = FV + SV ² . F and S were calculated from QCA data. F is the coefficient of pressure loss due to viscous friction (Poiseuille resistance), and S is the coefficient of local pressure loss due to abrupt enhancement (flow separation). V is coronary flow velocity. Distal coronary perfusion pressure (QCA-TP) is on the vertical axis and coronary flow velocity (V) as a ratio to normal flow at rest is on the horizontal axis. In this case, F was calculated as 0.38 (mm Hg s/cm), and S was calculated as 0.07 (mm Hg s ² /cm ² ) by coronary artery morphology, and coronary flow reserve (SFR) was calculated as 1.39 (intersection point). Normal coronary flow is determined to be 20 cm/s. In this case, ΔP = FV + SV ² = 0.38 × (20 × 1.39) + 0.07 × (20 × 1.39) ² = 64.66 mm Hg, QCA − TP = 100 − Δp = 100 − 64.66 = 35.34 mm Hg.

TPs were determined by software integrated in the CAAS II ( Figure 1 ). Gould et al have shown that the calculated pressure gradient (ΔP) across a stenosis can be described by the following simplified equation: ΔP = FV + SV ² . The coefficients F and S are determined by the morphology of the coronary stenosis. F is the coefficient of pressure loss due to viscous friction (Poiseuille resistance), and S is the coefficient of pressure loss due to exit separation (flow separation). Assuming that the normal coronary flow is defined as 20 cm/s, QCA-TP was defined as the following equation: QCA − TP = 100 − ΔP. Assuming that a patient has a mean arterial pressure of 100 mm Hg and a coronary flow that can increase to 5 times its value at rest without stenosis, one can then graphically determine the stenosis flow reserve (SFR) by plotting coronary pressure (distal to the stenosis) against relative coronary flow. Distal coronary pressure decreases nonlinearly as relative coronary flow increases until hyperemia. The intersection of the curve (100 − ΔP), with the line representing coronary perfusion pressure under hyperemia is the SFR of that region for the flow in the distal coronary vascular bed under conditions of hyperemia. QCA-TP was shown at the point (pressure) of SFR, which is the intersection point between the 2 lines ( Figure 1 ). A representative case is shown in Figure 1 . The time necessary to measure QCA-TP was only several seconds in addition to the QCA analysis.

Statistical analysis was performed using IBM SPSS Statistics, version 18.0 (IBM, Armonk, New York). Categorical variables were summarized using counts and percentages. Continuous variables were presented as mean ± SD. Receiver-operating characteristics curve analysis was used to identify the cut-off value predictive of functional myocardial ischemia. Difference between the 2 groups with and without FFR ≤0.8 was assessed with the chi-square test for categorical variables and with unpaired Student t -test for continuous variables. Multiple regression analysis was performed to identify the independent predictors of FFR. A value of p <0.05 was considered significance.

Results

QCA and FFR assessments included 98 left anterior descending arteries (LADs), 28 left circumflex arteries (LCs), and 26 right from 132 patients with stable angina pectoris. Baseline clinical characteristics are presented in Table 1 . The mean patient age was 70.0 ± 10.2 years and male gender was 70%. Lesion characteristics are presented in Table 2 . The mean values of percent diameter stenosis, FFR, and QCA-TP were 48.9% ± 14.9, 0.76 ± 0.14, and 65.3 ± 20.1 mm Hg, respectively. Intraobserver and interobserver error was −0.5 ± 8.6 mm Hg ( r = 0.96) and −4.5 ± 9.9 mm Hg ( r = 0.91), respectively.

Correlations between FFR and QCA-TP are shown in Figure 2 . FFR and QCA-TP had a significant positive correlation with coronary arteries overall ( r = 0.76, p <0.001, Figure 2 ). Even in each coronary artery, a good correlation was observed between FFR and QCA-TP ( Figure 3 ). Receiver-operating characteristics analysis showed each QCA-TP cut-off value that predicted functional myocardial ischemia (FFR ≤0.8): 72.8 mm Hg for the LADs (area under the curve [AUC] = 0.93), 60.5 mm Hg for the LCs (AUC = 0.88), and 64.4 mm Hg for the right (AUC = 0.94; Figure 4 ). These QCA-TP cut-off values predicted FFR-based myocardial ischemia with a high diagnostic accuracy ( Table 3 ).

Correlation between FFR and QCA-TP. A good correlation ( r = 0.705) was observed between translesion pressure and FFR.

Correlation between FFR and TP in each coronary artery. Each coronary artery showed correlations between TP and FFR (A , B , and C) . Especially in the LADs (r = 0.74) and right (r = 0.80), there were good correlations (A and C) .

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