Study Design and Population
This was a retrospective cohort study, adhering to the Strengthening the Reporting of Observational Studies in Epidemiology statement. The study protocol complied with the Declaration of Helsinki and was approved by Xinqiao hospital ethics committee, Army Medical University (Chongqing, China).
We evaluated 413 patients with true bifurcation lesion undergoing PCI who admitted to cardiology department between September 2016 and March 2019 in our hospital. The inclusion criteria were as follows: (1) de novo bifurcation disease, lumen stenosis ≥50%; (2) age ≥18 years old; (3) true coronary bifurcation lesions (Medina classification 1.1.1, 1.0.1, 0.1.1); (4) second-generation drug-eluting stent (DES) into the main vessel (MV) and balloon angioplasty in side branch (SB); (5) residual stenosis <50% after pre-dilation. The exclusive criteria were as follows: (1) previous PCI; (2) previous coronary artery bypass grafting (CABG); (3) acute myocardial infarction; (4) stenting in SB; (5) contraindications for dual antiplatelet therapy; (6) malignant disease; (7) arterial dissection; (8) severe calcified lesions that cannot be successfully dilated; (9) primary kidney diseases (including primary nephritis syndrome, primary nephrotic syndrome, interstitial nephropathy and hereditary nephropathy), severe hepatic dysfunction, bleeding and coagulation diseases. In our hospital, CABG was the only way of revascularization for unprotected left main disease (UPLM), so UPLM and its bifurcation were included in CABG. Finally, a cohort of 219 patients was enrolled in this study. According to balloon angioplasty strategy in SB, the subjects were divided into conventional balloon (CB) group (117 cases) and paclitaxel-coated balloon (PCB) group (102 cases).
PCI Procedure
Everolimus-coated DES (Promus Premier, Boston Scientific, Marlborough, USA) was implanted in MV. CB (Quantum Maverick, Boston Scientific, Marlborough, USA) or PCB (SeQuent Please, Braun Melsungen, Berlin, Germany) was used for SB angioplasty. Hydrophilic coating and lipophilic paclitaxel were evenly distributed on the balloon surface that made paclitaxel easier to penetrate from balloon surface to vascular intima [10]. After pre-dilation for MV and SB, if no dissection or type A/B dissection existed in SB and residual stenosis of SB was less than 30% with TIMI grade 3 blood flow; DES was firstly implanted into MV with guide wire or balloon for SB protection; guide wire passed the stent mesh to exchange; then balloon was utilized to dilate the ostial lesion and SB, respectively; the standard balloon to artery ratio (0.8-1: 1) was mandated in procedure. If pre-dilation was not successfully (C-F type dissection or TIMI grade 0 or 1 blood flow in SB), double-stent interventional strategy was directly performed (Culotte or Crush could be considered by means of the characteristics of bifurcation lesion).
Definition
Coronary bifurcation disease was the lesion with severe stenosis in the MV and SB, respectively or together [11]. True bifurcation lesions referred to the ones in which both the MV and SB were affected and corresponded to Medina classification 1.1.1, 1.0.1, and 0.1.1 [12]. Medina classification was based on the order of the proximal/distal MV and SB, and was displayed as with (1) or without (0) lesion [13]. Unprotected left main was defined as the absence of protective vessels that no collateral circulation was established or no CABG grafts [14]. Restenosis was defined as diameter stenosis ≥50% at follow-up. Late lumen loss (LLL) referred to the difference in MLD between stenting and follow-up [15]. Acute myocardial infarction refer to the fourth universal definition, when troponin value exceeds the 99th percentile upper reference limit and combines at least one of following characteristics: (1) symptoms of myocardial ischemia; (2) new changes in ischemic electrocardiogram or emerging pathological Q waves; (3) imaging evidence of new loss of viable myocardium or new regional wall motion abnormality [16]. Angina pectoris was defined as ischemic chest pain that drived readmission, based on symptom, electrocardiogram characteristics and troponin.
Data Collection and Follow-up
Clinical data were collected from medical records by trained physicians including demographic data, medical history, laboratory indicators and essential drug therapy. Coronary angiography data were independently assessed by two interventional cardiologists including bifurcation site, Medina classification, diameters, minimum lumen diameter (MLD) and lumen stenosis, and the two interventional cardiologists were blind as to treatment. All angiography was performed under the same standard conditions, and quantitative coronary analysis (QCA) was performed using the QAngio XA system version 7.3.74.0 (Medis Medical Imaging Systems, Leiden, Nertherlands) [17].
Primary outcomes and bifurcation lesions were included in the follow-up process. Primary outcomes were major adverse cardiovascular events (MACE) defined as the composite of cardiac death, nonfatal myocardial infarction and angina pectoris. Reassessment of bifurcation lesions involved MLD, LLL and restenosis for MV and SB, respectively. All patients had a 12-month follow-up for angiography and cardiovascular events after PCI, and related data were obtained from hospital records and by interviewing patients and their families.
Statistical Analysis
PASS software version 11.0 was used to calculate power and determined the sample size based on previous studies and our estimates [18, 19]. Calculation formula for sample size as follow: see formula 1 in the supplementary files.
Finally, each group needed 98 cases at least.
SPSS software version 24.0 (SPSS, Inc, Chicago, Illinois) was utilized for statistical analyses. Continuous variables were expressed as mean ± SD and categorical variables were expressed as frequencies with percentages. The t test was used to compare continuous data and differences in categorical data were assessed by the Chi-squared test or Fisher exact test (two-sided). Cox regression analyses were performed to evaluate the association of PCB angioplasty with SB restenosis and MACE. Multivariate Cox models were adjusted for established cardiovascular risk factors (age, male, hypertension, diabetes, smoking, hyperlipidemia, bifurcation site and Medina classification). P values of less than 0.05 were considered statistically significant.