The relationship between stent expansion conditions and clinical outcomes is not
completely understood. This prospective cohort study included patients who were
successfully implanted with second-generation drug-eluting stent in 2012 and
received follow-up angiography in 9-12 months. Stent over-expansion was defined
Percutaneous coronary intervention (PCI) is an effective treatment for coronary
artery stenosis. despite that the use of drug-eluting stents (DESs) markedly
reduce in-stent restenosis (ISR) and target lesion revascularization (TLR)
compared with the use of plane balloon angioplasty and bare-metal stents (Byrne et al., 2017; Nabel and Braunwald, 2012), isr remains an unsolved issue
clinically. stenting coronary artery injures the stented segment and triggers a
series of repair and/or inflammatory mechanisms, leading to proliferation of
vascular smooth muscle cells, neointimal hyperplasia, and resultant isr (Carter et al., 1994; Schwartz et al., 1992). previous studies showed that with the
introduction of the second-generation dess, isr was markedly reduced to
Based on the abovementioned hypothesis, in this cohort study, we aimed to examine the impact of stent expansion conditions on the long-term clinical outcomes in patients who received DES implantation.
This is a prospective cohort study. Patients and lesions with the following
criteria were considered eligible: 1) stable angina, unstable angina, or
non-ST-segmental elevation myocardial infarction (NSTEMI); 2) de novo significant
coronary stenosis treated with the 2nd generation DESs; 3) angiographic success
after stenting; and 4) completion of follow-up angiography 12
Patients and lesions with following criteria were excluded: 1) ST-segmental
elevation myocardial infarction (STEMI) within 4 weeks; 2) post-procedural stent
under-expansion; 3) serious renal insufficiency (eGFR
Stent over-expansion was defined as
A case for stent over-expansion. (A) Severe stenosis
with calcification in the anterior descending branch; (B) stent implantation; (C)
coronary angiography after post-dilation; (D) on magnification, the distal of the
stent is over-expanded (the dotted line is the diameter of the stent segment,
which was measured by QCA of 2.98mm, and the solid line is the diameter of the
reference vessel, which was measured by QCA of 2.52mm, and its ratio was 1.15
Flow chart. The subjects for comparison of angiography follow-up were lesions and subjects for comparison of clinical end points were patients. Abbreviation: PCI, percutaneous coronary intervention.
This study is approved by the Ethics Committee of Fujian Medical University Union Hospital (Research project approval ethics number is 2019KY053), and all patients provided written informed consent before enrollment.
All patients received a pretreatment of aspirin and clopidogrel at the loading dose. Intra-procedural heparin (70-100 U/kg) was administered intravenously at the beginning of PCI. Additional heparin boluses (1000 U) were given per hour to maintain an activated clotting time of 250-300 s. Post-procedurally, aspirin was maintained indefinitely, and clopidogrel was maintained for 12 months unless contraindicated. Low molecular weight heparin and platelet glycoprotein receptor antagonists were used at the discretion of the operators.
All stents were the 2nd generation DESs, including Resolute (Medtronic, Minneapolis, Minnesota), Xience V (Abbott Vascular, Santa Clara, California), Firebird2 (Microport, Shanghai, China), Excel (JW, Shandong, China), and Partner (Lepu, Beijing, China).
Stent size was chosen based on 1.0-1.1 folds of the distal reference vessel diameter. Overlapping stent to cover the whole lesion was allowed.
Coronary angiography was obtained pre- and post-procedurally, and at 1-year
follow-up after intracoronary injection of 200 ug nitroglycerin. Quantitative
coronary analysis (QCA) was performed in the stented segment (in-stent) and 5 mm
proximal or distal to the stented segment (in-segment) to measure the reference
vessel diameter (RVD) and minimal lumen diameter (MLD) in two
orthogonal angiographic views using an automated contour detection algorithm
(AW Workstation 4.3: GE Medical Systems, Milwaukee, WI). Acute
lumen gain (ALG) was calculated by post-procedural MLD minus pre-procedural MLD,
late lumen loss (LLL) by post-procedural MLD minus follow-up MLD, net lumen gain
(NLG) by follow-up MLD minus pre-procedure MLD and diameter stenosis percent
(DSP) by (RVD-MLD)/RVD
Clinical data were collected during hospital stay and by hospital visit or
telephone contact at 1, 3, 6, 9, and 12 months after discharge and annually
thereafter. Coronary angiographic follow-up was planned at 12
Technical primary endpoint was DSP, BRS, and LLL at 12-month follow-up angiography. The clinical primary endpoint was the major cardiac adverse event (MACE), including cardiac death, myocardial infarction (MI), target vessel/lesion revascularization (TLR/TVR), or stent thrombosis (ST). The secondary endpoint was the individual component of MACE.
MI was defined according to the fourth universal definition of MI (Thygesen et al., 2019). TLR/TVR was target vessel/lesion re-therapy either by PCI or CABG. ST was diagnosed according to the Academic Research Consortium definition (Cutlip et al., 2007).
All analyses were performed with SPSS (version 20.0, Chicago, IL, USA).
Data were expressed as mean
A total of 161 lesions of 123 eligible patients among 1024 patients who
underwent PCI using DESs at our center from January 2012 to September 2012 were
enrolled in this cohort. 75 (46.58%) stented lesions were over-expanded, whereas
86 were norm-expanded. 63 patients with
Clinical and procedural data: The baseline clinical characteristics were comparable between the two groups (Table 1). No significant differences were observed in the lesion’s features (location, morphology, length, and diameter stenosis), procedural parameters (pre-dilated, post-dilated, and implanted stent number and length) between the groups (Table 2). Stent maximum inflation pressure (OR = 1.22, 95% CI: 1.02 to 1.45, P = 0.032) was an independent predictor of stent over-expansion.
|Yes (N = 75)||No (N = 86)|
|Female, n (%)||8(10.67%)||15(17.44%)||0.22|
|Hypertension, n (%)||47(62.67%)||54(62.79%)||0.987|
|Diabetes, n (%)||17(22.67%)||23(26.74%)||0.55|
|Hyperlipidemia, n (%)||26(34.67%)||35(40.70%)||0.431|
|Smoker, n (%)||35(46.67%)||35(40.70%)||0.446|
|Family history, n (%)||1(1.33%)||4(4.65%)||0.226|
|Prior MI, n (%)||22(29.33%)||17(19.77%)||0.158|
|Prior PCI, n (%)||19(25.33%)||22(25.58%)||0.971|
|Stable angina, n (%)||20(26.67%)||25(29.10%)||0.735|
|Unstable angina, n (%)||34(45.33%)||39(45.35%)||0.998|
|NSTEMI, n (%)||21(28.00%)||22(25.58%)||0.729|
|Aspirin, n (%)||73(97.33%)||83(96.51%)||0.763|
|Clopidogrel, n (%)||75(100%)||86(100%)||-|
|Statins, n (%)||75(100%)||84(97.67%)||0.499|
|Abbreviations: BMI, body mass index; LVEF, left ventricular ejection fraction;
MI, myocardial infarction; PCI, percutaneous coronary intervention; NSTEMI, non
ST segment elevation myocardial infarction.Data were expressed as mean |
|Yes (N = 75)||No (N = 86)|
|Lesion location, n (%)||0.382|
|Lesion morphology, n (%)|
|Angulation ≥ 45°||5(6.67%)||5(5.81%)||0.823|
|Chronic total occlusion||9(12.00%)||8(9.30%)||0.584|
|Pre-dilation, n (%)||52(69.33%)||60(69.77%)||0.956|
|Stent number, n (%)||0.308|
|Stent length (mm)||37.24
|Maximal stenting pressure (atm)||14.68
|Post-dilation, n (%)||34(45.33%)||42(48.84%)||0.663|
|Maximal pressure (atm)||17.58
|The ratio of stented segment over reference artery diameter (S:A)||1.126
|Abbreviations: LAD, left anterior descending branch; RCA, right coronary artery; LCX, left circumflex; LM, left main; TIMI flow, thrombolysis in myocardial infarction flow.|
Angiographic results: Quantitative computer analysis
(QCA) measurements showed the lack of significant differences in the
pre-procedural RVD, MLD, and DSP between the groups. The post-procedural DSP was
significantly reduced with similar RVD and MLD in the over-expansion group.
However, follow-up DSP at 1-year was markedly increased with reduced MLD in the
over-expansion group. QCA also showed higher LLL (0.54
|Over-expansion||P value||Over-expansion||P value|
|Yes (N = 75)||No (N = 86)||Yes (N = 75)||No (N = 86)|
|Follow-up at 1-year|
|Binary restenosis at 1-year||6(8.0%)||3(3.5%)||0.306||7(9.3%)||5(5.5%)||0.55|
|Abbreviations: QCA, quantitative computer analysis; ALG, acute lumen gain; BRS,
binary restenosis; DSP, diameter stenosis percentage; LLL, late lumen loss; MLD,
minimal lumen diameter; NLG, net lumen gain; RVD, reference vessel diameter;
Clinical outcomes: In the long-term follow-up, cardiac death, MI, and ST were similar between the groups, Cumulative MACE (17.5% vs. 8.3%, P = 0.133) tended to be higher in the over-expansion group. TLR/TVR during the 7-year follow-up period (11.1% vs. 3.3%, P = 0.098) increased in the over-expansion group (Table 4). The Kaplan-Meier cumulative MACE-free survival had a better trend in terms of statistical differences in the norm-expansion group than in the over-expansion group (log-rank test; P = 0.083). The MACE-free rate during the 7-year follow-up period was 82.5% and 91.7% in the over-expansion and norm-expansion groups, respectively (Fig. 3).
Kaplan-Meier curves of time to freedom from MACE showed a worse tendency for statistical differences in the stent over-expansion group, which should be avoid. Abbreviation: MACE: major cardiac adverse event.
|Over-expansion group||Norm-expansion group||P value|
|MACE at 1-year||2(3.2%)||0||0.496|
|MACE at 3.5-year (42months)||4(6.3%)||0||0.119|
|MACE at 7-year||11(17.5%)||5 (8.3%)||0.133|
|Abbreviations: MACE, major adverse cardiac events; ST, stent thrombosis; TVR,
target vessel revascularization; *P |
To our knowledge, this work was the first monographic study to explore the
relationship between stent over-expansion (S:A
Stent norm-expansion is undoubtedly expected to have favorable outcomes, whereas
under-expansion leads to unfavorable outcomes whether bare metal stents or DESs
were used (Fujii et al., 2005; Nakamura et al., 2016). Numerous previous
studies showed that immediate residual stenosis of
In the BMS era, Peter et al. (Sick et al., 2003) conducted a prospective
cohort showing that optimal results regarding ST and ISR were achieved with mild
residual stenosis between 0% and 15% after stent implantation, but the
restenosis rates reached up to 30% at that time. For DESs, Marco et al. (Costa et al., 2008) cited the concept of geographical miss (GM) to first-generation
drug eluting stent era. Longitudinal GM indicates balloon injury or uncover
plaque. Axial GM indicates under- or over-expansion (S:A
In the present study, we found higher LLL and DSP at 1-year angiographic follow-up in the over-expansion group than in the norm-expansion group. This phenomenon did not support the results of previous studies that the bigger MLD led to less ISR. The three following mechanisms might contribute to this phenomenon. First, stent over-expansion causes vessel injury, and the degrees of both are positively correlated (Russo et al., 2007). Inflammation and repair/reaction to injury play a central role in ISR driven by fibroblast growth and smooth muscle cell hyperplasia (Byrne et al., 2015). Second, flow in overdilated vascular segment slows down and decreases the shear stress. Low shear stress causes intimal hyperplasia by upregulating adhesion molecules and chemoattractant chemokines and cytokines, enhancing injury-induced inflammation and shifting the smooth muscle cell to a synthetic phenotype (Koskinas et al., 2012). Third, stent over-expansion occasionally results in vessel dissection, hematoma, and stent fracture (Kan et al., 2016), thereby resulting in a poor consequence. These features could be invisible even if we included angiographically successful cases.
Another major concern is whether stent over-expansion and associated incremental LLL affect the long-term clinical outcomes. This study showed the higher cumulative occurrence of MACE during 7-year clinical follow-up in the over-expansion group than in the norm-expansion group. The increase in MACE was driven by TLR/TVR, which occurred frequently in the stent edges.
A high rate of stent over-expansion was observed in this study, which can be related to the inclusion of difficult lesions (38.51% type C lesions). Such high rate is also a reminder that stent over-expansion is common in clinical practice. The baseline in this study showed no difference, but the tendency of calcification, stent length, and stent maximum inflation pressure were highly evident in the over-expansion group. Regression analysis also confirmed that stent maximum inflation pressure is an independent predictor of stent over-expansion. High resistance lesion, such as calcium or high plaque burden lesion, can cause a “dogbone” effect. Long lesion occurs along with long taper vessel, and the balloon that is selected based on the middle part of the vessel is oversized for the distal part of the vessel. In such cases, stent over-expansion can be made by inducing high pressure with a semi-compliant balloon, which deserves further attention.
This study had several limitations. First, the nonrandomized single center study nature with a relatively small sample size could limit the confirmatory conclusions. Second, this study included only the patients with 1-year angiographic follow-up data instead of all comers. The potential confounders or selection bias that might affect the outcomes could not be completely ruled out despite that the baseline clinical and procedural characteristics were comparable between the groups. Third, we did not explore the impact of repairing and inflammation responses on the long-term outcomes and we failed to explain the underlying mechanisms. Therefore, future large-scale randomized trials are warranted to validate these results.
Stent over-expansion is associated with the significant increase in LLL and DSP at 1-year angiographic follow-up and with the increasing trend of cumulative MACE during 7-year clinical follow-up period compared to stent norm-expansion and should be avoided.
Yi Tao: data collection and analysis, data interpretation, drafting manuscript, final critical revision of the manuscript and final approval.
Zi-wen Zhao: data collection and analysis, data interpretation, drafting manuscript, final critical revision of the manuscript and final approval.
Liang-long Chen: designer of the study, data analysis, data interpretation, drafting manuscript, final critical revision of the manuscript and final approval.
This study was supported by the National Natural Science Foundation of China (mainly by Grant No. 81370311, partially by Grant No. 81670332) Scientic and Technological Innovation Project of Fujian Province (No. 2016Y9030). We thank them for support, also all the peer reviewers and editors for their opinions and suggestions.
The author declares no conflicts of interests.