Patients with stable or unstable angina pectoris, scheduled to undergo elective percutaneous coronary intervention for de novo lesions, were considered eligible. Documented ischemia had to be present. Lesions with a reference vessel diameter between 2.5mm and 3.5mm and lesion length of ≤ 24mm were eligible for participation in this study. Exclusion criteria consisted of heart failure (left ventricular ejection fraction<30%), acute myocardial infarction that was diagnosed as troponin-T elevation, left main artery disease, ostial lesion (impossible to assess with OCT), heavily calcified or thrombotic lesions, life expectancy<1 year, and known renal failure (creatinine>2mg/dL).

All patients were treated with aspirin 200mg and clopidogrel 300 to 600mg loading dose before the procedure, and 100 U/Kg of unfractionated heparin was injected intravenously to maintain an activated clotting time ≥ 250 s during the procedure. For the lesion preparation, the patient underwent predilation with an optimal sized balloon based on angiography (balloon-to-vessel ratio of 1.0), shorter than the intended length of PCB with nominal pressure inflation. Application of the PCB was decided by the interventional cardiologist performing the procedure based on the FFR measured after plain old balloon angioplasty (POBA).7 Under angiographic guidance, PCB (SeQuent Please, B. Braun; Melsungen, Germany) sized at 1.0 of balloon-to-vessel ratio was delivered as quickly as possible and inflated for 60seconds with nominal pressure. The use of glycoprotein IIb/IIIa inhibitors during the procedure was at the discretion of the operator.

Coronary angiographies were analyzed using the Cardiovascular Angiography Analysis System (CAAS 5.10, Pie Medical Imaging B.V.; Maastricht, The Netherlands) by an independent investigator who was blinded to clinical data before POBA, after PCB application, and at 9-month follow-up.

Optical coherence tomography was performed based at the operator's discretion, before the procedure, after POBA (just before PCB application) and at 9-months’ follow-up. Fourier-domain OCT (C7XR, LightLab Imaging, Inc.; Westford, Massachusetts, United States) was used with the nonocclusive technique. The catheter was advanced distal to the lesion over a conventional 0.014-inch guidewire, and images were obtained by motorized pullback at 20mm/s during continuous flushing of 20mL of contrast media. Offline OCT analysis was performed by a totally independent investigator (J.N. No) using proprietary software (LLI). After calibration for z-offset, 1 frame per 5 frames was analyzed, discarding images with an intervening side branch.

Fractional flow reserve was measured before, after POBA (before PCB application), and at 9-month follow-up but was not performed for subtotal (99% stenosis) lesions without a clinical indication. After intracoronary nitroglycerine injection of 200μg, FFR was measured using a 0.014-inch coronary pressure wire (PressureWire Certus, St. Jude Medical Systems; Uppsala, Sweden) far distal from the lesion under hyperemic conditions induced by intravenous adenosine infusion (140-180μg/kg/min).

All patients were scheduled to undergo clinical and angiographic follow-up at 9 months. Serial angiographic data, OCT images and FFR measurements were analyzed. Clinical outcomes were defined according to the Academic Research Consortium criteria.8 Binary restenosis was defined as a diameter stenosis ≥ 50% at angiographic follow-up. Late-luminal loss was defined as the difference in minimal luminal diameter between postprocedure and follow-up images in the same segment (in-segment). All outcomes were adjudicated by a clinical events committee.

Analyses were performed using SPSS 18.0 (SPSS Inc.; Chicago, Illinois, United States). Continuous variables are presented as the mean±standard deviation or median [interquartile range]. Continuous variables were compared between 2 groups using the paired Student t test or Wilcoxon signed rank test, as appropriate. Categorical variables are presented as counts and percentages and were compared using the chi-square or Fischer exact test, as appropriate. A 2-tailed P value of<.05 was considered statistically significant.

Between June 2012 and June 2013, 20 patients (21 lesions) with OCT images after POBA and at 9 months’ follow-up were included in this study (Figure 1). Baseline clinical and procedural characteristics are shown in Table 1.

Figure 1.

Flow chart of PCB application. Operators decided PCB or stent implantation based on FFR measurement after POBA. Of 45 PCB treated lesions, 21 were included in this OCT sub-study. FFR, fractional flow reserve; OCT, optical computed tomography; PCB, paclitaxel-coated balloon; PCI, percutaneous coronary intervention; POBA, plain old balloon angioplasty; TIMI, Thrombolysis In Myocardial Infarction.

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The angiographic quantitative coronary analysis data, FFR and clinical outcomes are presented in Table 2. All patients underwent angiographic follow-up. The reference vessel diameter was 2.68±0.34mm. Late luminal loss and net gain of the lesions were 0.01±0.21mm and 0.95±0.51mm, respectively. Minimal lumen diameter showed no difference between the post-PCB application and a 9 months’ follow-up (2.16±0.27mm vs 2.14±0.35mm; P=.761). There were no angiographic binary restenosis or adverse clinical events except for 1 case of nontarget lesion revascularization.

Four vessels had subtotal occlusion (99% stenosis), and FFR was not measured in these vessels. After balloon angioplasty, restored coronary flow was measured as an FFR value of 0.87±0.04 in all enrolled lesions. At 9 months’ follow-up, restored coronary flow was sustained without a significant decrease in FFR measurement (0.83±0.08). Serial FFR results are listed in Table 2 and Figure 2.

Figure 2.

Cumulative distribution curves. Serial FFR and MLAs are presented. The post-POBA FFR was not significantly different compared with that at 9 months’ follow-up. There was a significant increment in the MLA from post-POBA to 9 months’ follow-up. FFR, fractional flow reserve; MLA, minimal lumen area; POBA, plain old balloon angioplasty.

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Pre-POBA OCT images were not available in 12 lesions due to the inability to cross the lesions with the OCT catheter or poor contrast filling in total occlusions with the OCT catheter. However, 21 OCT post-POBA and follow-up data were available. Serial OCT findings and the percent changes are presented in Tables 3 and 4. Optical coherence tomography-based mean lumen area and lumen volume increased significantly from post-POBA to follow-up (4.52 vs 5.18mm2, P<.001 and 72.8 vs 93.8mm3, P=.001, respectively). Minimal lumen diameter and minimal lumen area increased significantly after POBA (1.5 vs 1.96mm, P=.001 and 1.77 vs 3.12mm, P=.001, respectively), with a further increase at 9 months (1.96 vs 2.22mm, P=.011 and 3.12 vs 3.90mm, P=.011, respectively). Mean and minimal lumen symmetry did not change between post-POBA and 9-month follow-up, possibly because of the healed dissections of the plaque. The median percent changes of the minimal lumen areas between pre- and post-POBA, and post-POBA and follow-up showed an increase of 75.2% [interquartile range, 37.2% to 164.7%], and 50.0% [interquartile range, 1.1% to 64.5%], respectively. Post-POBA dissections were sealed in 14 lesions (66.7%) at the 9-month follow-up with a decrease in the size of the dissected flaps (Table 3). The maximal thickness and length of residual dissected flaps at the cross-sectional images decreased significantly (0.67±0.29 mm vs 0.44±0.21mm, P<.001 and 1.34±0.71 mm vs 0.68±0.33mm, P<.001, respectively), as shown in Figure 3. The length of dissected flaps on longitudinal images also decreased significantly (11.9±8.7 mm vs 1.8±1.5mm, P<.001). There were no complications related to these procedures.

Figure 3.

A representative case treated with PCB. A 67-year-old woman had unstable angina, with near total occlusion of the left anterior descending coronary artery (A). She underwent PCB treatment with a 3.0/20mm SeQuent Please (B. Braun; Melsungen, Germany). After treatment, the artery showed minimal residual stenosis and a nonflow limiting type A dissection. Coronary angiography was performed immediately after balloon angioplasty (B) and at 2 months due to atypical chest discomfort (C) and at the 9-month follow-up (D). After balloon angioplasty, OCT revealed that the lumen was relatively well expanded, although the disrupted plaque was created (E). At 2 months, OCT demonstrated an enlarged lumen; the dissected flap was no longer visible (F). At 9 months, the lumen was well preserved and the area of disrupted plaque was completely healed (G). OCT, optical coherence tomography; PCB, paclitaxel-coated balloon. *Small septal branch. Bar = 1 mm.

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Firstly, selection bias may have occurred in individual cases. Additionally, patients with an ongoing acute coronary syndrome were not considered eligible for inclusion due to the complex nature of the study (ie, pre- and postprocedural FFR and OCT). Hence, only elective patients were included in the study. Secondly, although clinical and angiographic outcomes are promising, the nature of this registry that selectively applied PCB based on the FFR measured after POBA does not allow for comparison with a reference technique. Nonetheless, this registry study might strengthen the results of previous PCB studies. Thirdly, the number of patients included was relatively low. The serial changes in the OCT images including predilated lesion data were available only for 9 lesions. Fourthly, OCT acquisition was conducted after POBA (just before PCB application) and the size of inflated PCB was significantly larger than that of the inflated balloon. Therefore, PCB might have additionally modified the predilated lesion compared with the acquired OCT images. However, in this study, very sensitive techniques were used that allow for accurate assessment of the short- and mid-term mechanisms involved in restoring and maintaining coronary blood flow. In addition, this study did not target all lesions of coronary artery disease, and therefore, the results cannot be applied to patients beyond the inclusion criteria and study protocol.