A retrospective analysis was conducted from the all patients with CABD that underwent PCI utilizing culotte two-stent strategy in Taichung Veterans General Hospital from July 2008 to November 2015. The classification of CABD was sorted by Medina classification system and the true bifurcation disease was defined as Medina classification 1,1,1, 1,0,1, or 0,1,1. Exclusion criteria included a history of PCI for acute myocardial infarction (AMI) with cardiogenic shock, in-stent restenosis at coronary bifurcation, and bifurcations lesions treated with bare metal stent (BMS).

The standard technique of culotte stenting for CABD was employed and presented briefly as followings. After placement of the guiding catheter, 2 wires were inserted in the distal bed of the main and side branches. Balloon angioplasty was conducted by sequential inflation of a semi-compliant balloon in each branch using an equal size or down quarter size of reference vessel. After balloon angioplasty, the first stent was introduced in the branch which was a smaller branch, a more difficult branch to deliver originally or a difficult passing via stent strut after the first stent deployment, and deployed using regular pressure. Stent length was chosen in order to cover the proximal part before the bifurcation, and the distal part of the lesion in the branch. A third wire was used to recross the strut of the first stent and went into the main branch using the first side branch wire as a marker. Afterward, the first wire in the main was removed and a small balloon was used to open the struts and prepare the way for the second stent. In some cases, the operator would perform kissing balloon technique of main and side branches at this stage to reduce the retraction effect of stent opposite site when the stent strut was opened up. This was called first kissing balloon technique of culotte stenting. Afterward, a second stent of the same type as the first (but of different length if lesion length differed) was inserted crossing the strut of the first stent and placed in order to cover the proximal and distal parts of the main branch with overlapping of the first stent in the proximal part of the bifurcation. After deployment of this stent, a wire was rewired into the side branch via the second stent strut and the stent strut was opened up as previously described. At the end of culotte stenting, a simultaneous kissing balloon inflation was performed and usually indicated the second kissing balloon technique in the case that the first kissing balloon technique was done or final kissing balloon technique in the case which there was no first kissing balloon technique done. Drug-eluting stent (DES) for culotte stenting was conducted in all cases. DES used in this study included sirolimus-eluting stents [(Cypher family, Cordis Corporation, Johnson & Johnson, Warren, NJ,), (Ultimaster, Terumo Corporation, Tokyo, Japan), and (Orsiro, Biotronik AG, Buelach, Switzerland)], paclitaxel-eluting stents (Taxus family, Boston Scientific, Natick, MA), zotarolimus-eluting stent (Endeavor, Endeavor Resolute, and Endeavor Integrity, Medtronic, Santa Rosa, CA), everolimus-eluting stents [(Xience family, Abbott Vascular, Santa Clara, CA), and Promus family (Boston Scientific)], biolimus A9-eluting stents [(Nobori, Terumo Corporation, Tokyo, Japan), and (Biomatrix Flex, and Biomatrix Neoflex, Biosensors Interventional Technologies Pte Ltd., Singapore)]. Nobori, Ultimaster, Biomatrix Flex, Biomatrix Neoflex, and Orsiro were grouped together as biodegradable polymer DES in this study. The DAPT was prescribed before and after the index procedure with lifelong low-dose aspirin (100 mg) in addition to a thienopyridine (75 mg of clopidogrel daily or 90 mg of ticagrelor twice daily) for ideally 12 months but a minimum of 6 months following DES implantation.

The baseline demographic data, clinical outcomes included in-hospital mortality, and long-term mortality, myocardial infarction (MI), target lesion failure (TLF), target lesion revascularization (TLR), target vessel revascularization (TVR) and any revascularization were retrospectively reviewed in detail and collected from medical records in the hospital database. These patients had their regular clinical follow-up every 1 to 3 months according to their conditions at our hospital or returned to the clinics or CV outpatient department of other hospitals where they usually visited before and had regular follow-up. In-hospital outcomes were carefully retrieved by reviewing the medical records and charts, and the clinical outcomes in the post-hospitalized periods were inquired from the notes of outpatient department saved in the hospital database or phone call by the assistant researcher/nurse at study period in case the patients had clinical follow-ups at other hospital. MI is diagnosed by the criteria of universal definition [9] during the follow-up period. TLR is defined as any repeat percutaneous intervention of the target lesion or bypass surgery of the target vessel performed for restenosis or other complication of the target lesion. TVR is defined as any repeat percutaneous intervention or surgical bypass of any segment of the target vessel. TLF is defined as the combination of cardiac death, target vessel MI, or clinically driven TLR. Any revascularization is defined as any repeat percutaneous intervention or bypass surgery for restenosis of the target lesion, or de novo lesion(s) of the target vessel or non-target vessel. Repeated coronary angiography was clinically-driven performed if the patients presented typical angina and suspected a recurrent ischemia event within 1 year or ischemically-driven performed with evidence of coronary ischemia by non-invasive test more than 1 year after the last coronary intervention. (Reviewer #1, Comment #2 and Comment #5) The study protocol was reviewed and approved by the Institutional Review Board/Ethics Committee of Taichung Veterans General Hospital, Taichung, Taiwan.

From July 2008 to November 2015, there were 238 CABD patients undergone culotte two-stent technique in our institute. Of these patients, all DES were implanted for culotte two-stent technique. The baseline characteristics of culotte two-stent patients are shown in Table 1. Most of these patients were elderly, male gender, acute coronary syndrome (ACS) on admission and multiple vessel disease. The characteristics of bifurcation lesions were mostly located at left coronary artery (51.3%), categorized as true bifurcation lesion (92%) and calculated less than 70 degree of bifurcation angle (74.4%).

The observed in-hospital and after-discharge clinical outcomes are shown in Table 2.

Two hundred twenty-six of two hundred thirty-eight patients (94.9%) completed a medium 3.27 years (mean 3.55 ± 1.94 yr) follow up. The rates of in-hospital mortality and total mortality were 4.2 and 17.6%. Of them, 6 of 10 and 10 of 42 mortalities were caused by cardiac origin causes during the in-hospital and follow-up periods. At post-discharge follow-up, there were 14 (5.9%) cases myocardial infarction, 28 (11.8%) cases TLF, 27 (11.3%) cased TLR, and 40 (16.8%) cases TVR. 56 (23.5%) patients received any revascularization.

Among these CABD patients undergone culotte two-stents technique, patients with the LM bifurcation lesion had higher in-hospital and total mortalities than those with the non-LM bifurcation lesion (Table 3). In addition, patients with the LM bifurcation lesion had higher TLF compared to those with the non-LM bifurcation lesion. Prevalence of MI, TLR, TVR or any revascularization was not significantly different between them. “Reviewer #1, Comment #6”.

We further analyzed the factors to predict TLF, TVR and total mortality in our cohort study (Tables 4, 5 and 6). For TLF, we found that the angle of bifurcation ≥70° and body mass index (BMI) were positively independent predictors for TLF. For TVR, we found that diabetes mellitus (DM) was an independent predictor to predict TVR in our culotte two-stent patients. For total mortality, we found that statin therapy for hyperlipidemia, hemoglobin and ejection fraction (EF) were negatively independent factors associated to total mortality in our cohort study.

The present study has several limitations. First, this was an observational, retrospective, and cohort study, and there was no other group of two-stent strategy for comparison. As previously mentioned, culotte stenting technique was the majority for coronary bifurcation lesions at our institution and there would be limited patients with other two-stent strategy and thus the heterogeneity of patient groups would be significantly different in comparison. Secondly, the patient number was relatively too small to have powerful impact for clinical and safety endpoints. In addition, no regular angio follow-up but clinical driven angio follow up may underestimate the real prevalence of TLF/TLR/TVR even though we completed a high percentage (94.9%) of clinical follow-up during an intermediate-term period (medium 3.27 yr. follow-up).