- Email: [email protected]
Impact on myocardial reperfusion using the M-Guard stent in primary percutaneous coronary intervention for ST-elevation myocardial infarction
546
Letters to the Editor
[7] Dick F, Li J, Giraud MN, et al. Basic control of reperfusion effectively protects against reperfusion injury in a realistic rodent model of acute limb ischemia. Circulation 2008;118(19):1920–8. [8] Eikelboom JW, Hirsh J. Monitoring unfractionated heparin with the aPTT: time for a fresh look. Thromb Haemost 2006;96(5):547–52.
[9] Liu A, Dirsch O, Fang H, et al. HMGB1 in ischemic and non-ischemic liver after selective warm ischemia/reperfusion in rat. Histochem Cell Biol 2011;135(5):443–52. [10] Ling Y, Yang ZY, Yin T, et al. Heparin changes the conformation of high-mobility group protein 1 and decreases its affinity toward receptor for advanced glycation endproducts in vitro. Int Immunopharmacol 2011;11(2):187–93.
http://dx.doi.org/10.1016/j.ijcard.2014.07.027 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
Impact on myocardial reperfusion using the M-Guard stent in primary percutaneous coronary intervention for ST-elevation myocardial infarction Prodromos Anthopoulos a, Ioannis Alexanian b, Georgia Karabela c,⁎, Loukas Pappas d, Ioannis Antonellis e, Anastasios Salahas e, Antonios Polydorou f a
The Medicines Company, Zurich, Switzerland University Atticon General Hospital, Greece Athens Naval Hospital, 71, Dinokratous, Athens 11521, Greece d Kratikon Athens General Hospital, Greece e Evangelismos Athens General Hospital, Greece f Metropolitan Hospital, Greece b c
a r t i c l e
i n f o
Article history: Received 13 April 2014 Accepted 5 July 2014 Available online 11 July 2014 Keywords: M-Guard stent Primary percutaneous coronary intervention ST-elevation myocardial infarction Myocardial reperfusion Intracoronary thrombus
In recent years many strategies have been developed to treat intracoronary thrombus in patients suffering with ST-elevation myocardial infarction (STEMI) and who underwent primary percutaneous coronary intervention (pPCI) [1]. The M-Guard stent (MGS) (Ispira-MD, Israel) is a bare metal stent covered by an ultrathin polymer mesh sleeve on its external surface, designed to trap thrombus between the stent and the vessel wall, providing this way embolic protection and reducing vessel injury [2]. We evaluated the short and long term performances of this device, by comparing the angiographic and clinical results to a control group from the pre-MGS era in STEMI patients undergoing pPCI. We also assessed the MGS deliverability and feasibility in native coronary arteries with highly atherosclerotic and thrombus loaded lesions. Furthermore, we examined whether the benefit from the use of the MGS was independent from the use of thrombus aspiration (TA) during pPCI. 73 consecutive patients with STEMI that underwent pPCI were enrolled in this study provided that there was visible thrombus and no bifurcation lesions [63.4 ± 13.52 years, men: 53]. MGS was successfully placed in 68 patients and analysis includes these 68 patients. TA (24/68–35.29%) and balloon predilation (35/68–51.47%) were at the discretion of the operator. This group was retrospectively compared with 44 consecutive STEMI patients who underwent pPCI from September 2004 to May 2005, before the introduction of TA or the use of MGS and served as the control group.
⁎ Corresponding author at: Athens Naval Hospital, 71, Dinocratous, Athens, 11521, Greece. Tel.: +30 6937070862, +30 210 6557729; fax: +30 210 6520793. E-mail address: [email protected] (G. Karabela).
Continuous data were expressed as a mean + SD. Comparisons of continuous variables were performed using the unpaired Student t-test. Categorical variables were expressed as numbers or percentages and analyzed by the chi-square or Fisher exact test as appropriate. Univariate and multivariate stepwise logistic regression analyses were performed to identify independent predictors for post-procedural TIMI3 and MBG3. Cox proportional hazards regression was used to identify independent correlates of a 6-month follow-up period MACE. A P-value of b0.05 was deemed significant. Target vessel revascularization (TVR) was 0/68 at 30 days and 4/68 (5.88%) at 12 months. Cardiac deaths: 0/68 at 30 days and 2/68 at 12 months, both of them possibly from stent thrombosis. Final TIMI3 was achieved in 62/68 (91.17%). Final TIMI was 2.88 ± 0.53 in the MGS group vs. 2.53 ± 0.88 in the control group (p: 0.015). MBG was 2.36 ± 0.91 vs. 1.83 ± 1.21 (p: 0.009) at the end of the pPCI respectively. No-reflow phenomenon occurred in 2/68 patients vs. 8/44 (p: 0.008). The subgroup of patients from the MGS group that TA was not performed (MGS-noTAgroup) was also 44 individuals. Final TIMI III for them was 2.9 ± 0.3 vs. 2.53 ± 0.88 53 (p: 0.01) and MBG was 2.43 ± 0.88 vs. 1.83 ± 1.21 (p: 0.009), respectively. No-reflow phenomenon occurred in 0/44 patients in the MGS-noTA group vs. 8/44 (p: 0.006). In this study we demonstrated the efficacy and safety of MGS at 30 days and one year after pPCI in STEMI patients. The MGS significantly reduced the no-reflow phenomenon in the MGS group compared to the control group. Additional, the final TIMI flow and MBG were higher in the MGS group. This benefit seems to remain in the subgroup of patients in whom thrombus aspiration was not performed. Considering these aspects, we should point out the advantages of MGS compared to the other embolic protection devices: • There is no need for specific training for its deployment. • It can be used immediately without extra delay which is required for EPD deployment. • There is no flow disturbance during its implantation as the slow flow we see when the other EPD are used. • It traps a significant quantity of the thromboembolic material against the arterial wall, minimizing this way the distal embolization and slow flow or no-reflow phenomenon. • The prothrombotic intima material (activated heparane sulfate surface) is isolated from the blood stream thus terminating the ongoing thrombus formation process.
Letters to the Editor
We should also consider the difficulties that the operator has to overcome during the implantation of this stent. Passage of the MGS through tortuous, calcified or small diameter vessels is very challenging, if not impossible. The few cases, where we failed to advance the stent through the lesion, were shepherds crook type of RCA anatomy. Another important issue is the compromising of side branches by the presence of polymer mesh sleeve on its external surface. In addition, there are no data about its behavior in high-thrombotic volume, especially when no other EPD were used. In our study, there were a few cases with thrombus load grade five, where M-Guard was used with the aspiration catheter and the effectiveness of their combination was impressive, resulting in TIMI 3 flow with satisfactory blush score. The limitations of our study concern the relatively small number of patients, taking mostly into consideration the subgroup of patients from the MGS group that TA was not performed. Another aspect is also the lack of a randomized design.
547
In conclusion, in the setting of pPCI, MGS proved to be effective and safe with low TVR and low thrombosis rates at 1 and 12 months, considering the high risk group of STEMI patients. In addition, final TIMI flow and MBG are higher and the incidence of no-reflow is less. That benefit from its use is independent from the performance of TA in pPCI. The authors report no relationships that could be construed as a conflict of interest.
References [1] Vlaar Pieter J, Svilaas Tone, van der Horst Iwan C, et al. Cardiac death and reinfarction after 1 year in the Thrombus Aspiration during Percutaneous coronary intervention in Acute myocardial infarction Study (TAPAS): a 1-year follow-up study. Lancet 2008;volume 371(Issue 9628):1915–9 (7 June). [2] Kaluski Edo, Eugen Hauptmann Karl, et al. Coronary Stenting With MGuard: First – In- Man Trial. J Invasive Cardiol 2008;20:511–5.
http://dx.doi.org/10.1016/j.ijcard.2014.07.025 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
Intracoronary mesenchymal stem cell transplantation in patients with ischemic cardiomyopathy Jan Lakota a,⁎, Maria Dubrovcakova a, Roman Bohovic a, Eva Goncalvesova b a b
Cancer Research Institute SAS, Bratislava, Slovakia National Institute of Cardiovascular Diseases, Bratislava, Slovakia
a r t i c l e
i n f o
Article history: Received 14 April 2014 Accepted 5 July 2014 Available online 11 July 2014 Keywords: Mesenchymal stem cells Myocardial infarction Gene expression Cell growth
Dear Editor,
Mesenchymal stem cells have unique ability to detect the injured tissue and heal it. This is the main reason why they are commonly used in regenerative therapy. Their protective effect is mediated by a paracrine way, cell-to-cell contact and other unknown mechanisms [1]. The patient treatment after myocardial infarction by autologous MSC results in an increased ejection fraction. It is safe and feasible [2]. The similar result has been proven by intramyocardial stem cell injection in patients with ischemic cardiomyopathy. The result was a partial revitalization of the infarct area and a decrease of the endsystolic and end-diastolic volume in one year after the cell administration [3]. In the present pilot study, we have shown the difference in the MSC gene expression profile from healthy donors versus patients after myocardial infarction. Our aim was to gain a better under-
⁎ Corresponding author at: Laboratory of Molecular Oncology, Cancer Research Institute, SAS, Vlarska 7, 83391 Bratislava, Slovakia. E-mail address: [email protected] (J. Lakota).
standing of the therapeutic effect of autologous bone marrow-derived mesenchymal stem cells in patients with heart failure. Ten patients with advanced chronic heart failure as a result of ischemic cardiomyopathy were included in the study. All of them were males with mean age of 50 years (range 43–59). All had well documented history of anterior wall acute myocardial infarction (AMI). AMI occurred at median of 38 months prior to the entry to the study. In two patients reperfusion for AMI was performed using balloon angioplasty, in four patients with thrombolysis and in four patients no reperfusion was used. In four patients percutaneous coronary intervention with stenting (because of chronic hemodynamically significant coronary artery stenosis) was performed more than 4 months before the procedure. One patient was five years after CAGB. In two patients an implantable cardioverter defibrillator was implanted 3 and 4 years earlier. In five patients coronary angiography before the MSC injection showed nonsignificant stenoses in infarct related artery (LAD), the other five patients had coronary lesions on small LAD branches (not suitable for any intervention). Local institutional ethic committee approved the study protocol in November 2003. Written informed consent was obtained from all patients. Thirty milliliters of bone marrow blood was obtained from the posterior iliac crest under local anesthesia by a standard technique from the patients as well as from healthy donors. (The aim of MSC isolation from the healthy donors was to treat the recipient GvHD after HLA identical sibling stem cell transplantation). The MSC were isolated as described previously [4]. The obtained bone marrow blood was diluted with 70 ml of PBS (phosphate buffered saline) and centrifuged 900 ×g for 10 min at 20 °C. The sediments were resuspended in 30 ml PBS, overlaid (15 ml each) over 35 ml of Percoll solution (density 1073 g/ml) and centrifuged 900 ×g for 30 min at 20 °C. Mononuclear cells (MNC) at the interphase were removed, diluted with PBS to 50 ml and centrifuged 460 ×g for 10 min at 20 °C. The sediments were resuspended in PBS. The MNC were
Letters to the Editor
[7] Dick F, Li J, Giraud MN, et al. Basic control of reperfusion effectively protects against reperfusion injury in a realistic rodent model of acute limb ischemia. Circulation 2008;118(19):1920–8. [8] Eikelboom JW, Hirsh J. Monitoring unfractionated heparin with the aPTT: time for a fresh look. Thromb Haemost 2006;96(5):547–52.
[9] Liu A, Dirsch O, Fang H, et al. HMGB1 in ischemic and non-ischemic liver after selective warm ischemia/reperfusion in rat. Histochem Cell Biol 2011;135(5):443–52. [10] Ling Y, Yang ZY, Yin T, et al. Heparin changes the conformation of high-mobility group protein 1 and decreases its affinity toward receptor for advanced glycation endproducts in vitro. Int Immunopharmacol 2011;11(2):187–93.
http://dx.doi.org/10.1016/j.ijcard.2014.07.027 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
Impact on myocardial reperfusion using the M-Guard stent in primary percutaneous coronary intervention for ST-elevation myocardial infarction Prodromos Anthopoulos a, Ioannis Alexanian b, Georgia Karabela c,⁎, Loukas Pappas d, Ioannis Antonellis e, Anastasios Salahas e, Antonios Polydorou f a
The Medicines Company, Zurich, Switzerland University Atticon General Hospital, Greece Athens Naval Hospital, 71, Dinokratous, Athens 11521, Greece d Kratikon Athens General Hospital, Greece e Evangelismos Athens General Hospital, Greece f Metropolitan Hospital, Greece b c
a r t i c l e
i n f o
Article history: Received 13 April 2014 Accepted 5 July 2014 Available online 11 July 2014 Keywords: M-Guard stent Primary percutaneous coronary intervention ST-elevation myocardial infarction Myocardial reperfusion Intracoronary thrombus
In recent years many strategies have been developed to treat intracoronary thrombus in patients suffering with ST-elevation myocardial infarction (STEMI) and who underwent primary percutaneous coronary intervention (pPCI) [1]. The M-Guard stent (MGS) (Ispira-MD, Israel) is a bare metal stent covered by an ultrathin polymer mesh sleeve on its external surface, designed to trap thrombus between the stent and the vessel wall, providing this way embolic protection and reducing vessel injury [2]. We evaluated the short and long term performances of this device, by comparing the angiographic and clinical results to a control group from the pre-MGS era in STEMI patients undergoing pPCI. We also assessed the MGS deliverability and feasibility in native coronary arteries with highly atherosclerotic and thrombus loaded lesions. Furthermore, we examined whether the benefit from the use of the MGS was independent from the use of thrombus aspiration (TA) during pPCI. 73 consecutive patients with STEMI that underwent pPCI were enrolled in this study provided that there was visible thrombus and no bifurcation lesions [63.4 ± 13.52 years, men: 53]. MGS was successfully placed in 68 patients and analysis includes these 68 patients. TA (24/68–35.29%) and balloon predilation (35/68–51.47%) were at the discretion of the operator. This group was retrospectively compared with 44 consecutive STEMI patients who underwent pPCI from September 2004 to May 2005, before the introduction of TA or the use of MGS and served as the control group.
⁎ Corresponding author at: Athens Naval Hospital, 71, Dinocratous, Athens, 11521, Greece. Tel.: +30 6937070862, +30 210 6557729; fax: +30 210 6520793. E-mail address: [email protected] (G. Karabela).
Continuous data were expressed as a mean + SD. Comparisons of continuous variables were performed using the unpaired Student t-test. Categorical variables were expressed as numbers or percentages and analyzed by the chi-square or Fisher exact test as appropriate. Univariate and multivariate stepwise logistic regression analyses were performed to identify independent predictors for post-procedural TIMI3 and MBG3. Cox proportional hazards regression was used to identify independent correlates of a 6-month follow-up period MACE. A P-value of b0.05 was deemed significant. Target vessel revascularization (TVR) was 0/68 at 30 days and 4/68 (5.88%) at 12 months. Cardiac deaths: 0/68 at 30 days and 2/68 at 12 months, both of them possibly from stent thrombosis. Final TIMI3 was achieved in 62/68 (91.17%). Final TIMI was 2.88 ± 0.53 in the MGS group vs. 2.53 ± 0.88 in the control group (p: 0.015). MBG was 2.36 ± 0.91 vs. 1.83 ± 1.21 (p: 0.009) at the end of the pPCI respectively. No-reflow phenomenon occurred in 2/68 patients vs. 8/44 (p: 0.008). The subgroup of patients from the MGS group that TA was not performed (MGS-noTAgroup) was also 44 individuals. Final TIMI III for them was 2.9 ± 0.3 vs. 2.53 ± 0.88 53 (p: 0.01) and MBG was 2.43 ± 0.88 vs. 1.83 ± 1.21 (p: 0.009), respectively. No-reflow phenomenon occurred in 0/44 patients in the MGS-noTA group vs. 8/44 (p: 0.006). In this study we demonstrated the efficacy and safety of MGS at 30 days and one year after pPCI in STEMI patients. The MGS significantly reduced the no-reflow phenomenon in the MGS group compared to the control group. Additional, the final TIMI flow and MBG were higher in the MGS group. This benefit seems to remain in the subgroup of patients in whom thrombus aspiration was not performed. Considering these aspects, we should point out the advantages of MGS compared to the other embolic protection devices: • There is no need for specific training for its deployment. • It can be used immediately without extra delay which is required for EPD deployment. • There is no flow disturbance during its implantation as the slow flow we see when the other EPD are used. • It traps a significant quantity of the thromboembolic material against the arterial wall, minimizing this way the distal embolization and slow flow or no-reflow phenomenon. • The prothrombotic intima material (activated heparane sulfate surface) is isolated from the blood stream thus terminating the ongoing thrombus formation process.
Letters to the Editor
We should also consider the difficulties that the operator has to overcome during the implantation of this stent. Passage of the MGS through tortuous, calcified or small diameter vessels is very challenging, if not impossible. The few cases, where we failed to advance the stent through the lesion, were shepherds crook type of RCA anatomy. Another important issue is the compromising of side branches by the presence of polymer mesh sleeve on its external surface. In addition, there are no data about its behavior in high-thrombotic volume, especially when no other EPD were used. In our study, there were a few cases with thrombus load grade five, where M-Guard was used with the aspiration catheter and the effectiveness of their combination was impressive, resulting in TIMI 3 flow with satisfactory blush score. The limitations of our study concern the relatively small number of patients, taking mostly into consideration the subgroup of patients from the MGS group that TA was not performed. Another aspect is also the lack of a randomized design.
547
In conclusion, in the setting of pPCI, MGS proved to be effective and safe with low TVR and low thrombosis rates at 1 and 12 months, considering the high risk group of STEMI patients. In addition, final TIMI flow and MBG are higher and the incidence of no-reflow is less. That benefit from its use is independent from the performance of TA in pPCI. The authors report no relationships that could be construed as a conflict of interest.
References [1] Vlaar Pieter J, Svilaas Tone, van der Horst Iwan C, et al. Cardiac death and reinfarction after 1 year in the Thrombus Aspiration during Percutaneous coronary intervention in Acute myocardial infarction Study (TAPAS): a 1-year follow-up study. Lancet 2008;volume 371(Issue 9628):1915–9 (7 June). [2] Kaluski Edo, Eugen Hauptmann Karl, et al. Coronary Stenting With MGuard: First – In- Man Trial. J Invasive Cardiol 2008;20:511–5.
http://dx.doi.org/10.1016/j.ijcard.2014.07.025 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
Intracoronary mesenchymal stem cell transplantation in patients with ischemic cardiomyopathy Jan Lakota a,⁎, Maria Dubrovcakova a, Roman Bohovic a, Eva Goncalvesova b a b
Cancer Research Institute SAS, Bratislava, Slovakia National Institute of Cardiovascular Diseases, Bratislava, Slovakia
a r t i c l e
i n f o
Article history: Received 14 April 2014 Accepted 5 July 2014 Available online 11 July 2014 Keywords: Mesenchymal stem cells Myocardial infarction Gene expression Cell growth
Dear Editor,
Mesenchymal stem cells have unique ability to detect the injured tissue and heal it. This is the main reason why they are commonly used in regenerative therapy. Their protective effect is mediated by a paracrine way, cell-to-cell contact and other unknown mechanisms [1]. The patient treatment after myocardial infarction by autologous MSC results in an increased ejection fraction. It is safe and feasible [2]. The similar result has been proven by intramyocardial stem cell injection in patients with ischemic cardiomyopathy. The result was a partial revitalization of the infarct area and a decrease of the endsystolic and end-diastolic volume in one year after the cell administration [3]. In the present pilot study, we have shown the difference in the MSC gene expression profile from healthy donors versus patients after myocardial infarction. Our aim was to gain a better under-
⁎ Corresponding author at: Laboratory of Molecular Oncology, Cancer Research Institute, SAS, Vlarska 7, 83391 Bratislava, Slovakia. E-mail address: [email protected] (J. Lakota).
standing of the therapeutic effect of autologous bone marrow-derived mesenchymal stem cells in patients with heart failure. Ten patients with advanced chronic heart failure as a result of ischemic cardiomyopathy were included in the study. All of them were males with mean age of 50 years (range 43–59). All had well documented history of anterior wall acute myocardial infarction (AMI). AMI occurred at median of 38 months prior to the entry to the study. In two patients reperfusion for AMI was performed using balloon angioplasty, in four patients with thrombolysis and in four patients no reperfusion was used. In four patients percutaneous coronary intervention with stenting (because of chronic hemodynamically significant coronary artery stenosis) was performed more than 4 months before the procedure. One patient was five years after CAGB. In two patients an implantable cardioverter defibrillator was implanted 3 and 4 years earlier. In five patients coronary angiography before the MSC injection showed nonsignificant stenoses in infarct related artery (LAD), the other five patients had coronary lesions on small LAD branches (not suitable for any intervention). Local institutional ethic committee approved the study protocol in November 2003. Written informed consent was obtained from all patients. Thirty milliliters of bone marrow blood was obtained from the posterior iliac crest under local anesthesia by a standard technique from the patients as well as from healthy donors. (The aim of MSC isolation from the healthy donors was to treat the recipient GvHD after HLA identical sibling stem cell transplantation). The MSC were isolated as described previously [4]. The obtained bone marrow blood was diluted with 70 ml of PBS (phosphate buffered saline) and centrifuged 900 ×g for 10 min at 20 °C. The sediments were resuspended in 30 ml PBS, overlaid (15 ml each) over 35 ml of Percoll solution (density 1073 g/ml) and centrifuged 900 ×g for 30 min at 20 °C. Mononuclear cells (MNC) at the interphase were removed, diluted with PBS to 50 ml and centrifuged 460 ×g for 10 min at 20 °C. The sediments were resuspended in PBS. The MNC were