Abstract
Aim
Stents reduce angiographic restenosis in comparison with balloon angioplasty. The rate of in-stent restenosis (ISR), although less frequent than post-angioplasty restenosis, is becoming increasingly prevalent due to the recent exponential increase in the use of intracoronary stents. The aim of this study is to evaluate angiographic and clinical outcomes of PTCA in combination with the use of excimer laser coronary angioplasty (ELCA) and drug-eluting balloon (DEB) in treatment of in-stent restenosis (ISR).
Methods and results
This multi-centric case-control study evaluated angiographic and clinical outcomes of PTCA with excimer laser coronary angioplasty (ELCA) and drug-eluting balloon (DEB) in 80 patients with in-stent restenosis (ISR). All patients underwent nine months of clinical and a coronary angiography follow-up. This study showed clinical and angiographic long-term success in the 91% of the patients. The incidence of myocardial infarctions and deaths was lower than the rate after plain balloon angioplasty within the stent.
Conclusions
This study showed that excimer laser coronary angioplasty (ELCA) and drug-eluting balloon (DEB) may be an alternative treatment for in-stent restenosis (ISR).
Highlights
- •
The DERIST study is a multicenter study conducted in 6 centers in Italy;
- •
The study evaluate the results of treatment of in-stent restenosis (ISR) performed by the combined use of excimer laser (ELA) and drug-eluting balloon (DEB);
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The study evaluates the presence of new angiographic restenosis and the incidence of MACE in the study population.
1
Introduction
Stents reduce angiographic restenosis in comparison with balloon angioplasty . The rate of in-stent restenosis (ISR), although less frequent than post-angioplasty restenosis, is becoming increasingly prevalent due to the recent exponential increase in the use of intracoronary stents. Prior studies have shown that tubular slotted stents do not recoil and do not allow geometric arterial constriction, which may account for up to 55% of lumen loss in the restenotic process after angioplasty or atherectomy . Therefore, ISR is due to intimal hyperplasia . The introduction of drug-eluting stents (DES) has substantially reduced angiographic restenosis and target lesion revascularization (TLR) in comparison to bare-metal stents (BMS) . However, the higher complexity of the treated lesions and the increased off-label use of DES make the real world restenosis rate higher than the results reported from the clinical randomized trial . Numerous mechanisms can underlie the DES ISR pathophysiology such as:
- 1)
Biological factors: resistance to anti-proliferative drugs and hypersensitivity reactions;
- 2)
Technical factors: incomplete stent expansion, geographical miss, and barotraumas to un-stented segments;
- 3)
Mechanical factors: stent fractures, polymer peeling and non-uniform stent strut distribution or drug deposition.
Although ISR is often considered a benign process, recent data have shown that the clinical presentation can vary from stable angina to an acute coronary syndrome (ACS) . Treatment of in-stent restenosis (ISR) with conventional percutaneous transluminal coronary angioplasty (PTCA) causes significant recurrent neointimal tissue growth from 30–85% of cases. Therefore, the use of drug-eluting balloon (DEB) followed by laser ablation of intrastent neointimal hyperplasia can be an attractive alternative approach. However, the long-term outcomes of such treatments have not been studied thoroughly. This prospective and multi-centric study evaluated angiographic and clinical outcomes of PTCA in combination with the use of excimer laser coronary angioplasty (ELCA) and DEB.
2
Methods
This multi-centric case-control study evaluated angiographic and clinical outcomes of PTCA with excimer laser coronary angioplasty (ELCA) and DEB in 80 patients with ISR. Eighty patients with focal ISR were enrolled from January 2010 to January 2013. All patients underwent nine months of clinical and a coronary angiography follow-up. Excimer laser angioplasty and drug-eluting balloon were used to treat in stent restenosis lesions with high success rate. To assess immediate and long-term results of patients treated, we analyzed demographic information and the immediate results of 80 patients who underwent ELCA and DEB. The patients were followed up and assessed for clinical restenosis.
2.1
Patient characteristics
In this study, 80 consecutive patients were prospectively included. Written informed consent was obtained from all patients under a protocol approved by the ethics committee of the Avellino Medical Board. Patients were included if they presented with an in-stent restenosis or a wire able total occlusion within a stent that had been implanted for one month into a native vessel or a coronary artery vein graft. Patients with an evolving myocardial infarction, angiographic evidence of fresh thrombus or lesions in segments with major bifurcations on visual assessment were excluded. The mean age of the 80 patients was 65 ± 10 years (range: 39–76 years); 59 patients were men. Major coronary risk factors were: diabetes mellitus (33 patients/38%) (non-insulin dependent: n 21 [31%], insulin dependent: n 12 [15%]), hyperlipoproteinemia (59 patients/73%), arterial hypertension (65 patients/75%), current or recently stopped smoking (51 patients/63%) and a family history of coronary artery disease (53 patients/62%). The patient group had a high prevalence of known risk factors for recurrent restenosis ( Table 1 ). A previous or current total occlusion was present in 23 patients (24%). The stents had been implanted for recurrent restenosis in 21 patients (26%). All stents implanted were drug-eluting stents (DES). In 14 patients stents were located in venous bypass grafts (17%). Multiple stents (>2 stents/vessel) had been implanted in 52 patients (65%). Stents were located in small vessels (<3.00 mm in diameter) in 52 patients (65%). Excimer laser angioplasty was performed within 112 coronary stents. The stents had been implanted for 6 ± 3 months (range: 2–16 months) before the time of intervention ( Table 2 ). There was no intracoronary imaging or FFR used, for the difficulty to cross coronary complex lesion of this study with FFR or intracoronary imaging devices.
| Patient characteristics |
|---|
| □ The mean age of the 80 patients was 65 ± 10 years (range: 39–76 years); 59 patients were men. |
| □ Major coronary risk factors were: |
| • Diabetes mellitus (33 patients/38%) |
| Non-insulin dependent: n 21 (31%) |
| Insulin dependent: n 12 (15%) |
| • Hyperlipoproteinemia (59 patients/73%) |
| • Hypertension (65 patients/75%) |
| • Current or recently stopped smoking (51 patients/63%) |
| • Family history of coronary artery disease (53 patients/62%) |
| Patient characteristics |
|---|
| □ The patient group had a high prevalence of known risk factors for recurrent restenosis. |
| □ A previous or current total occlusion was present in 23 patients (24%). |
| □ The stents had been implanted for recurrent restenosis in 21 patients (26%). All stents implanted were drug-eluting stents (DES). |
| □ In 14 patients, stents were located in venous bypass grafts (17%). |
| □ Multiple stents (>2 stents/vessel) had been implanted in 52 patients (65%). |
| □ Stents were located in small vessels (<3.00 mm in diameter) in 52 patients (65%). |
| □ Excimer laser angioplasty was performed within 112 coronary stents. |
| □ The stents had been implanted for 6 ± 3 months (range: 2–16 months) before the time of intervention. |
2.2
Procedural features
- A)
Excimer laser system and adjunctive balloon angioplasty. A xenon chloride excimer laser unit operating at a wavelength of 308 nm (Spectranetics CVX-300, Colorado Springs, Colorado) was used in all patients. The laser unit delivered laser pulses of 135 ns pulse duration at a frequency (repetition rate) of 25–45 Hz and an energy density (fluence) of 30–60 mJ/mm 2 . The laser energy was delivered through concentric multifiber laser catheters (Turboelite RX; Spectranetics Corp., Colorado Springs, Colorado) with tips ranging from 0.9, 1.4, and 1.7 mm in diameter. Intracoronary saline infusion was initiated 3 s before delivery of laser energy and was continued during excimer laser treatment. Multiple passes were performed at the operator’s discretion to achieve maximum debulking. Adjunctive balloon angioplasty was performed in all patients using standard techniques.
- B)
Use of drug-eluting balloon. After performed, ELCA has used 93 drug-eluting balloons (Amphirion inpact Medtronic) (DEB). DEB was used as the last step for the lesion treatment with no further ballooning done after DEB to ensure maximum availability of the drug delivered to the vessel wall. The DEB was inflated at the site of ISR for 60 s at its nominal pressure. If the lesion length was large and such a size was not available, then two short-length DEBs were used sequentially to completely cover the lesion. Angioplasty was considered adequate at <20% residual stenosis.
- C)
Medical treatment before, during and after ELCA. Pretreatment medication consisted of oral aspirin 100 mg/day (or 300 mg aspirin, if the patient was not on aspirin therapy before). A standard angioplasty regimen of heparin (10.000 IU intravenous bolus injection) and intracoronary nitroglycerin (100–200 mg) was given before angiography was performed. The permanent medical treatment after the intervention consisted of oral aspirin 100 mg/day.
2.3
Inhospital results
No acute post procedural complications were observed, including no-reflow and dissection. During the hospital stay, four patients still had angina symptoms and were managed medically.
2.4
Clinical follow-up
Clinical evaluation at six-month follow-up included the record of cardiac adverse events and clinical symptoms defined as: death (death for cardiac or any other cause), myocardial infarction (ST segment elevation 0.10 mV in two electrocardiographic leads plus creatine kinase elevation two times above normal value associated with 6% creatine kinase MB fraction or the development of new pathologic Q waves in the electrocardiogram according to the Minnesota Code) . At this time, the occurrence of angina pectoris, graded according to the classification of the Canadian Cardiovascular Society (CCS) , was registered.
2
Methods
This multi-centric case-control study evaluated angiographic and clinical outcomes of PTCA with excimer laser coronary angioplasty (ELCA) and DEB in 80 patients with ISR. Eighty patients with focal ISR were enrolled from January 2010 to January 2013. All patients underwent nine months of clinical and a coronary angiography follow-up. Excimer laser angioplasty and drug-eluting balloon were used to treat in stent restenosis lesions with high success rate. To assess immediate and long-term results of patients treated, we analyzed demographic information and the immediate results of 80 patients who underwent ELCA and DEB. The patients were followed up and assessed for clinical restenosis.
2.1
Patient characteristics
In this study, 80 consecutive patients were prospectively included. Written informed consent was obtained from all patients under a protocol approved by the ethics committee of the Avellino Medical Board. Patients were included if they presented with an in-stent restenosis or a wire able total occlusion within a stent that had been implanted for one month into a native vessel or a coronary artery vein graft. Patients with an evolving myocardial infarction, angiographic evidence of fresh thrombus or lesions in segments with major bifurcations on visual assessment were excluded. The mean age of the 80 patients was 65 ± 10 years (range: 39–76 years); 59 patients were men. Major coronary risk factors were: diabetes mellitus (33 patients/38%) (non-insulin dependent: n 21 [31%], insulin dependent: n 12 [15%]), hyperlipoproteinemia (59 patients/73%), arterial hypertension (65 patients/75%), current or recently stopped smoking (51 patients/63%) and a family history of coronary artery disease (53 patients/62%). The patient group had a high prevalence of known risk factors for recurrent restenosis ( Table 1 ). A previous or current total occlusion was present in 23 patients (24%). The stents had been implanted for recurrent restenosis in 21 patients (26%). All stents implanted were drug-eluting stents (DES). In 14 patients stents were located in venous bypass grafts (17%). Multiple stents (>2 stents/vessel) had been implanted in 52 patients (65%). Stents were located in small vessels (<3.00 mm in diameter) in 52 patients (65%). Excimer laser angioplasty was performed within 112 coronary stents. The stents had been implanted for 6 ± 3 months (range: 2–16 months) before the time of intervention ( Table 2 ). There was no intracoronary imaging or FFR used, for the difficulty to cross coronary complex lesion of this study with FFR or intracoronary imaging devices.
