Abstract
Aim
To assess feasibility and 1-year outcomes of ultrathin biodegradable polymer double stenting using a very minimal crushing (nano-crush technique) in a series of patients with large (≥2.5 mm) complex coronary bifurcation.
Methods
From January 2015 to June 2016, patients referred for large (≥2.5 mm) complex coronary bifurcation percutaneous coronary interventions (PCI) were enrolled to receive Orsiro (Biotronik Inc., Bulack, Switzerland) double stenting using a very minimal crush technique (nano-crush). Per our institutional protocol, follow-up was conducted by physical examination at 1, 6, 12 month and yearly whereas angiographic control was eventually scheduled at 6–8 months on the basis of symptoms recurrence or/and positive induced ischemia tests.
Results
Fifty-two patients (15 females mean age 77.2 ± 6.2 years) were enrolled. Mean angles between main branch and side branch were 63.6 ± 21.3°. The mean diameter and length of implanted stents were 3.8 ± 0.4 mm and 27.1 ± 8.7 mm in main branch and 2.8 ± 0.3 mm and 22.1 ± .7.1 mm in side branch. Immediate success was 100%. Clinical follow-up was available for 100% of patients: at a mean follow-up of 12.0 ± 2.6 months, no patient death, or acute myocardial infarction or target vessel revascularization were observed. Angiographic follow-up was available in 25/52 patients (48%) at a mean time from the procedure of 7.2 ± 0.5 months and showed no significant angiographic restenosis.
Conclusions
The revascularization of complex large (≥2.5 mm) coronary bifurcation disease using the nano-crush technique and the ultrathin polymer biodegradable stent appeared feasible in our small study with promising 1 year outcomes.
1
Introduction
Randomized trials of coronary bifurcation stenting have shown better outcomes from a simple (provisional) strategy rather than a complex (planned two-stent) strategy in terms of short-term efficacy and safety . Nevertheless, large complex bifurcations have been suggested to be better approached by a planned double stent technique . Critical issues for long-term outcomes after double stenting appear to be the amount of metal layer at the carena and bifurcation angle which both possibly are the major drawbacks of either Culottes’ and DK crush.
Last generation of DES, and in particular the ultrathin cobalt–chromium biodegradable polymer Orsiro stent (Biotronik Inc., Bulack, Switzerland) , thanks to the very thin struts (60 μm up to 3.0 mm diameter stent and 80 μm up to 4.0 mm stent), might have the potential to improve the overall results . Techniques aimed to decrease as much as possible the amount of metal inside the bifurcation and possibly applicable to both any diameter ratio between main vessel/side branch and to any bifurcation angle, seem another critical issue impacting in adverse events and stent thrombosis rate .
Therefore we assessed the feasibility of Orsiro ultrathin biodegradable polymer double stenting in large (≥2.5 mm) coronary bifurcation using a very minimal crush (nano-crush) technique in a preliminary series of patients.
2
Methods
From 1° January 2015 to 1° June 2016, large (≥2.5 mm) complex coronary bifurcation percutaneous coronary interventions (PCI) were enrolled to receive Orsiro double stenting using a very minimal crush technique (nano-crush). Complex bifurcations have been defined following DEFINITION (Definitions and impact of complEx biFurcation lesIons on clinical outcomes after percutaNeous coronary IntervenTIOn using drug-eluting steNts) study .
Patients were analyzed on the basis of clinical (cardiovascular risk factors, Canadian Cardiovascular Score class, EUROSCORE ) and angiographic characteristics (lesion/s location and severity according to the SYNTAX score and MEDINA classification ).
Any Medina 1,1,1 and 0,1,1 coronary bifurcation lesions with an SB diameter ≥ 2.5 mm by visual estimation, including unprotected left main, independently from clinical presentation, were enrolled in the study. Exclusion criteria were considered: 1) SB diameter < 2.5 mm; 2) contraindications for dual antiplatelet therapy; 3) life-expectance less than 24 months.
Written informed consent was obtained from all patients, and the hospital department board approved the study.
2.1
Percutaneous coronary intervention protocol
A 6F right radial approach has been selected whenever possible. During PCI, patients were anticoagulated with unfractionated heparin (a bolus of 40 U/kg and additional heparin to achieve an activated clotting time of 250–300 s).
Additional significant lesions in other vessels were treated with staged procedures and a routine third generation DES of the operator’s choice (Promus Premier, Boston Scientific, Galway, Ireland; Orsiro, Biotronik, Bulack, Switzerland; Resolute Integrity, Medtronic Inc., Galway, Ireland). Twelve-month Ticagrelor or Prasugrel treatment and life-long aspirin were recommended to all patients.
2.2
IVUS protocol
Intravascular Ultrasound examination was performed routinely following current guidelines using the 3 F Opticross coronary IVUS catheter (Boston Scientific, Fremont, CA, USA) and automatic pull-back system (0.5 mm/s). On-line ultrasound assessment was performed in diastole. IVUS images were recorded after administration of 100–200 mg of nitroglycerin. The ultrasound catheter was advanced .5 mm beyond the lesion/stent and was pulled back to a point .5 mm proximal to the lesion/stent using motorized transducer pullback at 0.5 mm/s. IVUS was performed and interpreted by the treating physician and at least one experienced IVUS technician.
The lumen cross sectional area (CSA) at the stent level was assessed by planimetry at the interface of the blood and the stent, at multiple levels (at least three), and the smallest area was chosen. The proximal and distal reference lumen areas and diameters were also measured by manual planimetry. The reference segments were selected as the most normal-looking cross section within 10 mm proximal and distal to the stent. To reduce the variability, all IVUS measurements were repeated, and the average of the two values was used in the analysis. Routine measurements were recorded pre- and post-stent implantation . On follow-up IVUS control particular attention was carried out in determining stent thrombosis or restenosis.
IVUS parameters at baseline, post stent, and on eventual follow-up, were correlated to FFR to verifying the lesion significance and the achieved results using the AVIO criteria .
2.3
Nano-crush technique
The very minimal or so-called “Nano-crush” stenting technique is a modification of the classical T-stent or Crush where the aim is to crush just one single cell of the stent protruding into the main vessel (around 0.5–1 mm at maximum) using an ultrathin stent in order to minimize as much as possible the amount of metal crushed preserving coverage of the side branch ostium. The technique includes two variants: the standard nano-crush as resumed in Fig. 1 and the reverse nano-crush as resumed in Fig. 2 have been used depending on side branch accessibility and size of the distal main branch and side branch. If the side branch is particularly difficult to wire or if the diameter of the distal main branch equalizes the proximal side branch a reverse nano-crush rather than standard nano-crush has been used. Both variants included high pressure (>20 at) proximal optimization technique (POT) after main branch stent implantation, high pressure snuggle kissing, and Re-POT as the final step.
2.4
Definitions
Quantitative coronary angiographic (QCA) analysis at baseline, post-stenting and at follow-up was performed using edge detection techniques (CAAS II 5.0 version; Pie Medical, Maastricht, Netherlands). Angiographic success was defined as residual stenosis 30% by visual analysis in the presence of thrombolysis in myocardial infarction (TIMI) 3 flow grade. Binary restenosis was defined as stenosis ≥50% of the luminal diameter in target lesions. Angiographic measurements included the stented segment as well as the margins 5-mm proximal and distal to the stent.
Major adverse cardiac events were defined as (1) death, (2) nonfatal myocardial infarction (MI), or (3) target vessel revascularization (TVR). All deaths were considered to be of cardiac origin unless a noncardiac origin was established clinically or at autopsy. AMI was diagnosed by a rise following Thygesen K et al. . TVR was defined as a repeated intervention (surgical or percutaneous) to treat a luminal stenosis within the stent or in the 5-mm distal or proximal segments adjacent to the stent, including the ostium of the left anterior descending artery (LAD) and/or circumflex artery. Stent thrombosis was classified according to the Academic Research Consortium (ARC) definitions as definite, probable or possible, as early (0–30 days), late (31–360 days) or very late (>360 days).
In-stent restenosis (ISR) was classified as focal (<10 mm long), diffuse (>10 mm long), proliferative (>10 mm long and extending outside the stent edges), or totally occluded . Information about in-hospital outcomes was obtained from an electronic clinical database for patients maintained at our institution and by review of hospital records for those discharged to referring hospitals. Post-discharge survival status was obtained from the Municipal Civil Registries. Information on occurrence of AMI or repeated interventions at follow-up was collected by consulting our institutional electronic database and by contacting referring physicians and institutions and all living patients.
2.5
Clinical follow-up
Per our institutional protocol, follow-up was conducted by physical examination at 1, 6, and 12 months and then yearly. Induced ischemia test by means of Ergometric test, nuclear stress test or stress echocardiography was scheduled at 6/8 months. Transthoracic echocardiography was scheduled at 6 months. Angiographic and intravascular ultrasound control was scheduled at 6/8 months, at the time of additional vessel treatment or driven by clinical symptoms or instrumental evidence of myocardial ischemia. Information about in-hospital outcome was obtained from an electronic clinical database for patients maintained at our institution and by review of hospital records for those discharged to referring hospitals. Post-discharge survival status was obtained from the Municipal Civil Registries. Information on the occurrence of AMI or repeated interventions at follow-up was collected by consulting our institutional electronic database and by contacting referring physicians and institutions and all living patients.
2.6
Statistical analysis
Continuous variables are described as mean ± standard deviation, and categorical variables are described as proportions. Statistical analysis was performed using a statistical software package (SAS for Windows, version 8.2; SAS Institute; Cary, NC). A probability value of <0.05 was considered to be statistically significant.
2
Methods
From 1° January 2015 to 1° June 2016, large (≥2.5 mm) complex coronary bifurcation percutaneous coronary interventions (PCI) were enrolled to receive Orsiro double stenting using a very minimal crush technique (nano-crush). Complex bifurcations have been defined following DEFINITION (Definitions and impact of complEx biFurcation lesIons on clinical outcomes after percutaNeous coronary IntervenTIOn using drug-eluting steNts) study .
Patients were analyzed on the basis of clinical (cardiovascular risk factors, Canadian Cardiovascular Score class, EUROSCORE ) and angiographic characteristics (lesion/s location and severity according to the SYNTAX score and MEDINA classification ).
Any Medina 1,1,1 and 0,1,1 coronary bifurcation lesions with an SB diameter ≥ 2.5 mm by visual estimation, including unprotected left main, independently from clinical presentation, were enrolled in the study. Exclusion criteria were considered: 1) SB diameter < 2.5 mm; 2) contraindications for dual antiplatelet therapy; 3) life-expectance less than 24 months.
Written informed consent was obtained from all patients, and the hospital department board approved the study.
2.1
Percutaneous coronary intervention protocol
A 6F right radial approach has been selected whenever possible. During PCI, patients were anticoagulated with unfractionated heparin (a bolus of 40 U/kg and additional heparin to achieve an activated clotting time of 250–300 s).
Additional significant lesions in other vessels were treated with staged procedures and a routine third generation DES of the operator’s choice (Promus Premier, Boston Scientific, Galway, Ireland; Orsiro, Biotronik, Bulack, Switzerland; Resolute Integrity, Medtronic Inc., Galway, Ireland). Twelve-month Ticagrelor or Prasugrel treatment and life-long aspirin were recommended to all patients.
2.2
IVUS protocol
Intravascular Ultrasound examination was performed routinely following current guidelines using the 3 F Opticross coronary IVUS catheter (Boston Scientific, Fremont, CA, USA) and automatic pull-back system (0.5 mm/s). On-line ultrasound assessment was performed in diastole. IVUS images were recorded after administration of 100–200 mg of nitroglycerin. The ultrasound catheter was advanced .5 mm beyond the lesion/stent and was pulled back to a point .5 mm proximal to the lesion/stent using motorized transducer pullback at 0.5 mm/s. IVUS was performed and interpreted by the treating physician and at least one experienced IVUS technician.
The lumen cross sectional area (CSA) at the stent level was assessed by planimetry at the interface of the blood and the stent, at multiple levels (at least three), and the smallest area was chosen. The proximal and distal reference lumen areas and diameters were also measured by manual planimetry. The reference segments were selected as the most normal-looking cross section within 10 mm proximal and distal to the stent. To reduce the variability, all IVUS measurements were repeated, and the average of the two values was used in the analysis. Routine measurements were recorded pre- and post-stent implantation . On follow-up IVUS control particular attention was carried out in determining stent thrombosis or restenosis.
IVUS parameters at baseline, post stent, and on eventual follow-up, were correlated to FFR to verifying the lesion significance and the achieved results using the AVIO criteria .
2.3
Nano-crush technique
The very minimal or so-called “Nano-crush” stenting technique is a modification of the classical T-stent or Crush where the aim is to crush just one single cell of the stent protruding into the main vessel (around 0.5–1 mm at maximum) using an ultrathin stent in order to minimize as much as possible the amount of metal crushed preserving coverage of the side branch ostium. The technique includes two variants: the standard nano-crush as resumed in Fig. 1 and the reverse nano-crush as resumed in Fig. 2 have been used depending on side branch accessibility and size of the distal main branch and side branch. If the side branch is particularly difficult to wire or if the diameter of the distal main branch equalizes the proximal side branch a reverse nano-crush rather than standard nano-crush has been used. Both variants included high pressure (>20 at) proximal optimization technique (POT) after main branch stent implantation, high pressure snuggle kissing, and Re-POT as the final step.
