Abstract
Objectives
To evaluate feasibility and safety of MGuard based percutaneous coronary interventions (PCI) in vein grafts (VG) and native coronaries (NC).
Background
Distal embolization is a frequent complication of PCI of VG and NC during acute coronary syndromes (ACS). MGuard was a stent designed to reduce embolization.
Methods
Prospective, single arm, two-center trial assessing the feasibility and safety of MGuard-based PCI with post-PCI clinical and laboratory monitoring including: cardiac biomarkers, ECG and 6-month angiography.
Results
Forty-one patients with mean age of 68.2±10.1 years were enrolled. Mean VG age ( n =23) was 14.4±4.3 years. All patients received heparin, clopidogrel and aspirin; while none received glycoprotein IIb/IIIa inhibitors, or embolic protection device (EPD). Device and procedural success were 100% and 95.1% respectively. Two patients (4.9%) experienced procedure-related creatinine phosphokinase rise. At 6 months one patient had myocardial infarction and 19.5% had target vessel revascularization (TLR). Late follow up (12-27 months) revealed one additional TLR.
Conclusion
MGuard based PCI of NC and VG appears encouraging especially in view of unfavorable patient and lesion characteristics. Efficacy needs to be further established in larger randomized trials.
1
Introduction
Distal embolization during and after the percutaneous interventions continues to compromise procedural results in embolization prone clinical scenarios (like acute coronary syndromes and acute ischemic stroke), embolization susceptible vascular beds (degenerated vein grafts, carotid and renal arteries) or pathologies (aneurysms).
MGuard (Inspire-MD, Tel-Aviv, Israel) is a stainless steel closed cell design stent (slotted-tube, laser-cut) with strut thickness of 80-95 μm (for stent diameters of 3-3.5 and 4-4.5 mm respectively) covered on its external (abluminal) surface by an ultra-thin Polyethylene theraphthalate (PET or Dacron) mesh sleeve ( Fig. 1 ). This mash is fabricated by circular knitting and is anchored to the external surface of the stent. During stent deployment, the net stretches and slides over the expanding stent struts, creating custom-designed pores of ≤200 micron in diameter (Pores created by stent struts have 5–40-fold larger diameter, translating into 25–1600-fold larger cross-sectional area). The microfiber net (string diameter 20 micron) has minimal effects (<0.1 mm) on the stents’ crossing profile and deliverability. By trapping the thromboembolic debris underneath the fiber net MGuard isolates the prothrombotic subintimal components from the luminal blood stream.
Upon conclusion of coronary porcine trials that reflected excellent feasibility and satisfactory safety , Inspire-MD decided to initiate human safety trials. The purpose of the study was to evaluate the safety and feasibility of MGuard based PCI in distal embolization prone vascular beds: old degenerated VG and NC culprit lesions in patients experiencing ACS. In a previous manuscript , we reported the results of the first 29 patients with 6 months follow-up. In this report, we provide the data regarding 41 patients with a follow up of 12–27 months. We also provide the data from an independent quantitative coronary angiography core lab (assessing baseline angiography, the procedural outcome, and the 6 months angiographic results).
2
Methods
2.1
General
Prospective, single-arm, two-center (Helios Heart Center, Siegburg and Department of Cardiology Krankenhaus der Barmherzigen Brüder Trier) trial to assess the feasibility and safety in a high-risk PCI cohort of NC (preferably with ACS) and degenerated VG.
2.2
Patients
2.2.1
Included
Included were symptomatic patients with NC or degenerated VG de-novo lesions with diameter stenosis ≥50% but <100%, reference vessel diameter ≥2.5 and ≤4.5 mm, TIMI flow ≥1, and willing to sign an informed consent.
2.2.2
Excluded
Patients with suspected or known allergy to aspirin, clopidogrel, contrast, or heparin; requirement to treat ≥1 coronary lesion urgently; LVEF <25%, stroke, or transient ischemic attack within 60 days; baseline creatinine phosphokinase (CPK) values greater than three times the upper limit of normal; and creatinine ≥2.0 mg/dl, excessive proximal vessel calcification or tortuousity and a recent bleeding event were excluded.
2.3
Procedure
The following procedures were done to secure eligibility: history, physical examination, ECG, cardiac isoenzymes (troponin I, CPK and CPK-MB), complete blood count, full chemical profile, and pregnancy test if relevant. Candidates for the procedure were screened informed about the study and consented to participate in the study 24 h prior to PCI. Patient was pre-medicated with aspirin (≥100 mg, ≥24 h pre-PCI) and clopidogrel (≥600 mg ≥4 h pre-PCI). Nitroglycerine (100 μg intracoronary) was administered prior to baseline and final coronary angiographies. PCI was executed employing conventional equipment. The use of additional adjunctive pharmacotherapy and devices (including balloon pre and post dilatation) was left at the discretion of the investigators.
The investigators were instructed to (a) perform pre-dilatation with “undersized” balloon (2 mm) prior to MGuard deployment; (b) if multiple MGuard stents were used, stenting from distal to proximal with no overlap was preferred; (c) bailout with additional conventional stents was an option in case of distal dissection or “geographic miss.”
Cardiac isoenzymes (Troponin I, CPK and CPK-MB were obtained 6–8, 12–16, and 24 h post procedure. Post-PCI patients received aspirin (100 mg daily indefinitely) and clopidogrel (75 mg daily for ≥6 months). Twelve-lead ECG was recorded 6-8 and 24 h post-PCI and at 1- and 6-month follow-up visits. Follow-up appointments were scheduled at 1 month and 6 months post PCI. The latter visit included follow-up angiogram.
Following the original protocol conclusion, an extended follow-up was approved by the local institutional review board and conducted. The new exploratory endpoint was major adverse cardiac events (MACE) at maximal follow-up period (≥12 months). All Patients were contacted again and asked to release medical information about their condition beyond the duration of the original 6 month follow-up. In case of MACE events, medical records were collected from the relevant medical centers.
2.4
Study endpoints
2.4.1
Primary endpoints included
Thirty-day MACE included cardiac death, myocardial infarction (defined as chest pain and CPK rise exceeding three times upper limit of normal), stent thrombosis (Academic Research Consortium definition), bypass surgery, and repeat target lesion or vessel revascularization.
2.4.2
Secondary endpoint included
2.4.2.1
Device success
There was successful delivery and deployment of the MGuard stent to target lesion.
2.4.2.2
Procedural success
Conclusion of PCI with satisfactory results in the absence of in-hospital MACE.
2.4.2.3
Clinical success
There was procedural success in the absence of 30-day MACE.
2.4.3
Data collection and statistical analysis
Demographic, clinical, and medical data were collected using an electronic Case Report Form (CRF) system and was routinely monitored for protocol adherence, compliance, and quality by independent monitors (Kraut, Germany).
All angiograms (baseline, 6-month, and any adverse event-related angiograms) were analyzed by an independent core-lab (Cardiology Research Foundation, New York, NY, USA). Adverse events as well as patient’s eligibility were evaluated by an independent clinical events committee.
Baseline and safety data were summarized descriptively. Baseline characteristics of the study cohort and MACE were based on “intention-to-treat” data set.
2.4.4
Ethical and compliance issues
The study was approved and executed under the supervision of local institutional review boards according to “Good Clinical Practice” guidelines as well as the “German Devices Law” (Medizinproduktegesetz MPG), and international standard IN ISO 14155, “clinical evaluation of medical devices on humans.”
2
Methods
2.1
General
Prospective, single-arm, two-center (Helios Heart Center, Siegburg and Department of Cardiology Krankenhaus der Barmherzigen Brüder Trier) trial to assess the feasibility and safety in a high-risk PCI cohort of NC (preferably with ACS) and degenerated VG.
2.2
Patients
2.2.1
Included
Included were symptomatic patients with NC or degenerated VG de-novo lesions with diameter stenosis ≥50% but <100%, reference vessel diameter ≥2.5 and ≤4.5 mm, TIMI flow ≥1, and willing to sign an informed consent.
2.2.2
Excluded
Patients with suspected or known allergy to aspirin, clopidogrel, contrast, or heparin; requirement to treat ≥1 coronary lesion urgently; LVEF <25%, stroke, or transient ischemic attack within 60 days; baseline creatinine phosphokinase (CPK) values greater than three times the upper limit of normal; and creatinine ≥2.0 mg/dl, excessive proximal vessel calcification or tortuousity and a recent bleeding event were excluded.
2.3
Procedure
The following procedures were done to secure eligibility: history, physical examination, ECG, cardiac isoenzymes (troponin I, CPK and CPK-MB), complete blood count, full chemical profile, and pregnancy test if relevant. Candidates for the procedure were screened informed about the study and consented to participate in the study 24 h prior to PCI. Patient was pre-medicated with aspirin (≥100 mg, ≥24 h pre-PCI) and clopidogrel (≥600 mg ≥4 h pre-PCI). Nitroglycerine (100 μg intracoronary) was administered prior to baseline and final coronary angiographies. PCI was executed employing conventional equipment. The use of additional adjunctive pharmacotherapy and devices (including balloon pre and post dilatation) was left at the discretion of the investigators.
The investigators were instructed to (a) perform pre-dilatation with “undersized” balloon (2 mm) prior to MGuard deployment; (b) if multiple MGuard stents were used, stenting from distal to proximal with no overlap was preferred; (c) bailout with additional conventional stents was an option in case of distal dissection or “geographic miss.”
Cardiac isoenzymes (Troponin I, CPK and CPK-MB were obtained 6–8, 12–16, and 24 h post procedure. Post-PCI patients received aspirin (100 mg daily indefinitely) and clopidogrel (75 mg daily for ≥6 months). Twelve-lead ECG was recorded 6-8 and 24 h post-PCI and at 1- and 6-month follow-up visits. Follow-up appointments were scheduled at 1 month and 6 months post PCI. The latter visit included follow-up angiogram.
Following the original protocol conclusion, an extended follow-up was approved by the local institutional review board and conducted. The new exploratory endpoint was major adverse cardiac events (MACE) at maximal follow-up period (≥12 months). All Patients were contacted again and asked to release medical information about their condition beyond the duration of the original 6 month follow-up. In case of MACE events, medical records were collected from the relevant medical centers.
2.4
Study endpoints
2.4.1
Primary endpoints included
Thirty-day MACE included cardiac death, myocardial infarction (defined as chest pain and CPK rise exceeding three times upper limit of normal), stent thrombosis (Academic Research Consortium definition), bypass surgery, and repeat target lesion or vessel revascularization.
2.4.2
Secondary endpoint included
2.4.2.1
Device success
There was successful delivery and deployment of the MGuard stent to target lesion.
2.4.2.2
Procedural success
Conclusion of PCI with satisfactory results in the absence of in-hospital MACE.
2.4.2.3
Clinical success
There was procedural success in the absence of 30-day MACE.
2.4.3
Data collection and statistical analysis
Demographic, clinical, and medical data were collected using an electronic Case Report Form (CRF) system and was routinely monitored for protocol adherence, compliance, and quality by independent monitors (Kraut, Germany).
All angiograms (baseline, 6-month, and any adverse event-related angiograms) were analyzed by an independent core-lab (Cardiology Research Foundation, New York, NY, USA). Adverse events as well as patient’s eligibility were evaluated by an independent clinical events committee.
Baseline and safety data were summarized descriptively. Baseline characteristics of the study cohort and MACE were based on “intention-to-treat” data set.
2.4.4
Ethical and compliance issues
The study was approved and executed under the supervision of local institutional review boards according to “Good Clinical Practice” guidelines as well as the “German Devices Law” (Medizinproduktegesetz MPG), and international standard IN ISO 14155, “clinical evaluation of medical devices on humans.”
3
Results
Forty-one patients were enrolled between October 2006 and February 2008. Twenty-three (56%) with VG interventions and 18 (44%) with NC PCIs; 78% were males, 39% diabetic, 76% hypertensive, 83% hyperlipidemic and 37% were smokers. Other patients’ baseline characteristics are shown in Table 1 .
| No. of patients | 41 |
| Age , y | 68.2±10.1 |
| Male | 32 (78) |
| Height, cm | 171.5±6.8 |
| Weight, kg | 80.3±10.7 |
| Body mass index | 27.3±3.6 |
| Diabetes mellitus | 16 (39) |
| Insulin dependant | 4 (10) |
| Non-Insulin dependant | 12 (29) |
| Hypertension | 31 (76) |
| Hyperlipidemia | 34 (83) |
| Smoking | 15 (37) |
| Current | 7 (17) |
| Former | 8 (20) |
| Angina | 20 (49) |
| Stable | 15 (37) |
| Unstable | 5 (12) |
| Family history of coronary artery disease | 12 (29) |
| Prior MI | 12 (29) |
| Prior PCI | 21 (51) |
| Prior CABG | 28 (68) |
| History of congestive heart failure | 9 (22) |
All patients received Clopidogrel during the full 6 months of the initial follow-up. Medication use pre PCI and during the follow-up period are shown in Table 2 .
| Baseline | |
| Aspirin | 98% |
| Clopidogrel | 66% |
| beta-Blockers | 78% |
| Satins | 76% |
| Pre procedure loading | |
| Aspirin | 100% |
| Clopidogrel | 100% |
| Intra procedure | |
| Nitroglycerin | 76% |
| Heparin | 100% |
| Glycoprotein IIb/IIIa inhibitor | 0% |
| Discharge | |
| Aspirin | 100% |
| Clopidogrel | 100% |
| 30 days | |
| Aspirin | 98% |
| Clopidogrel | 100% |
| 6 months | |
| Aspirin | 95% |
| Clopidogrel | 100% |
Device success was 100% while procedural and clinical success was 95.1% and 92.7%, respectively. Procedural and angiographic characteristics and events are described in Table 3 .
| VG lesion | 56.1% (23) |
|---|---|
| VG age | 14.4±4.3 years |
| EPD used | 0% (0/23) |
| Stents per lesion | 1.2 |
| Lesion length | 15.19±6.30 mm |
| Pre-RVD | 3.26±0.56 mm |
| Pre-MLD | 0.84±0.46 mm |
| Pre-%DS | 74%± 12% |
| Post-MLD | 2.86±0.55 mm |
| Post-%DS | 12%±7% |
| Post-acute gain | 2.01±0.53 mm |
| TIMI 0–1 (pre/post) | 4.9%/0.0% |
| TIMI 2 (pre/post) | 17.1% (7)/2.4% (1) |
| TIMI 3 (pre/post) | 78.0%/97.6% |
| No reflow | 0.0% (0) |
| Slow flow | 2.4% (1) |
| Distal embolization | 0.0% (0) |
3.1
Primary and secondary endpoints
The 30-day MACE rate was 7.3%: two patients had periprocedural creatine kinase-MB rise ≥3 times upper limit of normal ( Table 4 ). None of these events were associated with reduced coronary flow or evidence of embolization on the angiogram. One patient experienced myocardial infarction within 30 days of PCI. This event was related to stent thrombosis occurring within 2 additional conventional (none-MGuard) stents deployed in the target vessel 1 week after the MGuard procedure in view of concern regarding distal dissection.
| Event | In hospital | Up to 30 days | Up to 6 months | Extended follow-up |
|---|---|---|---|---|
| MACE, % ( n ) | 4.9 (2) | 7.3 (3) | 22 (9) | 24.4 (10) |
| Death, % ( n ) | 0 (0) | 0 (0) | 2.4 (1) | 2.4 (1) |
| Cardiac death, % ( n ) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
| Stent thrombosis, % ( n ) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
| Q-wave MI, % ( n ) | 0 (0) | 2.4 (1) | 2.4 (1) | 2.4 (1) |
| Non Q-wave MI, % ( n ) | 4.9 (2) | 4.9 (2) | 4.9 (2) | 4.9 (2) |
| PCI TLR | 0 (0) | 2.4 (1) | 19.5 (8) | 22 (9) |
| Coronary bypass | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
3.2
Follow up
Between 1 and 6 months, there was one noncardiac death not related to the device or the procedure. Cumulative MACE for the duration of the follow-up is summarized in Table 4 .
3.3
Six-month angiography data ( Table 5 )
At the 6-month follow-up visit, 36 patients (88%) agreed to undergo angiography, which showed a Binary restenosis of 22.2% and late loss of 0.79±0.79 mm. The 6-month MACE rate was 22% and was driven by target vessel revascularization (TLR) of 19.5% (most of which were related to restenosis detected during 6-months angiography and not clinically driven but). The Kaplan-Meier curves of freedom from myocardial infarction and TLR are displayed by Figs. 2 and 3 respectively.
