Methods
Study Population
Sixty-six patients with a coronaryde novo lesion and concomitant PCI and stent implantation due to stable angina and/or documented ischemia on stress test were enrolled in the present analysis between August 2011 and September 2013.
All lesions were investigated by OCT and FFR before and immediately after stent implantation. Clinical history, laboratory tests, and QCA analysis were performed in all patients. Inclusion criteria were the presence of a coronary stenosis, eligible for OCT and FFR examination, written informed consent to the study protocol, and conformation to institutional guidelines. Exclusion criteria were left main, bifurcation, serial and bypass graft lesions, acute coronary syndromes, left ventricular ejection fraction (LVEF) <30%, contraindications to adenosine administration, hemodynamic, or rhythmic instability, renal insufficiency (serum creatinine level >1.5 mg/dL), and pregnancy.
The study was approved by the local Ethics Committee and was in accordance with the Declaration of Helsinki on ethical principles for medical research involving human subjects.
Quantitative Coronary Angiography
We performed standardized QCA after intracoronary administration of nitrates (200 μg) and recorded two orthogonal views of every major coronary vessel. QCA data analysis included reference lumen diameter, minimal lumen diameter (MLD), percent diameter stenosis, and lesion length. These data were determined by an experienced reader. Offline imaging analysis was performed with a validated QCA software (Philips Inturis Cardio View, QCA V3.3; Pie Medical Imaging).
Follow-up
Clinical follow-up was obtained by telephone contact or during outpatient visits. A major adverse cardiac event (MACE) was classified as any death, myocardial infarction (MI)/non-ST elevation myocardial infarction (NSTEMI), or target lesion revascularization (TLR) within the follow-up period. In case of more than one clinical event in a single patient, the first event was taken for analysis. The decision for recatheterization and TLR was based on the interventionalist's discretion.
FFR Measurements
FFR measurements were performed using a 0.014" coronary pressure sensor-tipped Certus wire (St. Jude Medical Systems, AB) and were in accordance with the recently published recommendations for standardization, recording, and reporting of FFR measurements. Maximal hyperemia was induced by intracoronary administration of 200 μg adenosine. FFR was calculated as the ratio between intracoronary and aortic pressure. Preinterventional stenoses were considered to be hemodynamically relevant if FFR was ≤0.8. The FFR guidewire was hereafter used for stent implantation. Accuracy of postinterventional FFR measurements was assured by assessing the pressure curves as previously described. In case of a suspected drift between aortic and pressure-wire pressures, the FFR sensor was pulled back to the guiding catheter and equalization of pressures was performed again. Postinterventional FFR was determined distal to the stent as described above if coronary angiography documented an optimal interventional result, defined as ≤10% residual diameter stenosis by visual estimation. If FFR did not normalize after PCI, FFR was measured proximally to the stent to exclude a relevant lesion of the native proximal vessel segment. In the case of a persistent trans-stent gradient ≤0.8, an FFR delta <0.1 compared to the baseline FFR value, or stent malapposition documented by OCT, additional balloon inflation with a non-compliant balloon was performed. Final FFR measurement for analysis was taken when FFR was >0.8, FFR delta was ≥0.1, and adequate stent apposition and/or maximum balloon burst pressure was achieved.
OCT Image Acquisition and Analysis
OCT image acquisition was performed using the frequency-domain OCT C7XR system and the DragonFly catheter (St. Jude Medical Systems; Lightlab Imaging, Inc). The removal of blood was achieved with the non-occlusion OCT technique by injection of iodixanol iso-osmolar contrast (GE Healthcare) through the guiding catheter, followed by an automated pull-back at a rate of 20 mm/s. The required amount of contrast was 10–15 mL/pullback at a flow rate of 4 mL/s, and the cumulative examination time was approximately 3 minutes for each single OCT image acquisition.
Subsequent offline and pull-back analyses were performed by two independent observers as previously described and in accordance with the recently published consensus for quantitative and qualitative assessment. The analysts were blinded to the clinical and interventional results; in cases of divergent results, they reached a consensus measurement.
The following quantitative and qualitative assessments were taken before intervention:
Minimal lumen area (MLA) and MLD at the frame with the smallest intraluminal area.
Reference lumen area at the reference cross-section with the largest lumen within 10 mm proximal or distal to the MLA and before any side branch. Percent area stenosis (%AS) was calculated as ([reference lumen area – MLA]/reference lumen area) x 100.
Stenosis length, measured as the segment around the MLA with a cross-sectional area of at least 50% compared to the predefined reference segment lumen area.
The OCT examination was performed after the initial stent deployment and was repeated in the case of a documented stent malapposition after every consecutive additional balloon dilatation. Definite postinterventional OCT acquisition for data analysis was performed after final balloon inflation and after final FFR measurement, and encompassed the frame with the smallest intraluminal area within the stented segment (defined as the minimal stent area [MSA]). The intraluminal contour area and stent contour area were documented in this cross-sectional image (Figure 1). The maximal stent area (SA) was defined as the frame with the largest stent contour area within the entire stent. Intrastent %AS was calculated as ([maximal SA – minimal intraluminal contour area]/maximal SA) x 100. Tissue prolapse was defined as a convex-shaped protrusion of tissue between adjacent stent struts toward the lumen without disruption of the continuity of the luminal vessel surface.Thrombus was defined as an irregular mass with dorsal shadowing, protruding into the lumen without connection to the vessel wall. Moreover, stent edge dissections were recorded within 5 mm adjacent to the stent at the proximal and distal segment of the native vessel.
(Enlarge Image)
Figure 1.
(A) Optical coherence tomography (OCT)–derived cross-section with visible tissue prolapse between adjacent stent struts in the frame with the smallest intraluminal area within the stent. (B) The amplified image displays the intrastent minimal lumen area (inner blue contour) and the stent contour area (outer white contour).
Statistical Analysis
Statistical analyses were performed with SPSS (IBM Corporation). Categorical variables were summarized as count (percentage), continuous variables as mean ± standard deviation. Continuous variables were compared with Wilcoxon-Mann-Whitney, Student's or Welch's t-test, contingent on distributional characteristics. Pearson's χ test was used to test for the association of nominal variables.
Linear regression analysis was performed to determine the association between post-stenting OCT-derived parameters and FFR. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and optimal cut-off values were calculated from the receiver operating characteristic (ROC) curve to predict MACE rate at 20 months. This follow-up time of 20 months was predetermined in this study as a suitable clinical intermediate follow-up time for MACE. Given that the mean follow-up of our patient cohort was 15.11 ± 7.70 months (Table 1), cases with a shorter follow-up time and without events were included in the analysis as censored cases.
Assuming a MACE rate of 10% over 20 months of follow-up and a true area under ROC curve of 0.8, a total of 58 patients (ie, 6 events) are required to test the null hypothesis H0 (area under curve [AUC] = 0.5) vs the alternative hypothesis HA (AUC >0.5) with a power of 80%. A similar sample size was used in other studies investigating the effect of FFR and clinical outcome.
Values with the highest Youden index (sensitivity + specificity – 1) were identified as optimal cut-off values. A classification of the diagnostic efficiency of FFR and intrastent %AS according to the values of the AUC was used, as described elsewhere. MACE rates were estimated using the Kaplan-Meier method and differences in time-to-event distributions between groups were compared using the log-rank test. A P-value <.05 was considered statistically significant.