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{{CMG}}, '''Associate Editor(s)-In-Chief''' [[User :Raviteja Reddy Guddeti| Raviteja Reddy Guddeti, M.B.B.S.]]
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==Overview==
==Overview==
Bioabsorbable [[stents]] also known as ''the disappearing stents'' are a promising new discovery in the field of [[Interventional Cardiology]].They have been an interesting field of research over the past decade and half.As the name suggests they get absorbed completely over a period of time after their work has been done.The concept of bioabsorbable stents came into existence because there have been some unmet needs by the traditional bare metal [[stents]], such as [[thrombosis]],no drug platform,interfering with MRI-CT imaging,life long presence of implant and not facilitating reintervention.<br>  
Bioabsorbable [[stents]], also known as the disappearing stents, are a promising new discovery in the field of [[interventional cardiology]]. They have been an interesting field of research over the past decade and half. As the name suggests they get absorbed completely over a period of time after their work is done. Percutaneous coronary intervention ([[PCI]]) using bioabsorbable [[stents]] has created special interest because the mechanical support for the healing artery is required only for a brief period of time, and also the presence of a bare metallic prosthesis has potential disadvantages beyond the first few months.<ref> http://circinterventions.ahajournals.org/content/2/3/255.full</ref> <ref name="pmid16446520">{{cite journal |author=Waksman R |title=Biodegradable stents: they do their job and disappear |journal=J Invasive Cardiol |volume=18 |issue=2 |pages=70–4 |year=2006 |month=February |pmid=16446520 |doi= |url=}}</ref>
 
==Classification==
Bioabsorbable stents can be broadly classified into two types: polymeric and metallic types. The key features to be considered while selecting a polymer or an alloy for a bioabsorbable stent are:
* Strength in order to avoid potential immediate recoil
* Rate of degradation and corrosion
* Biocompatibility with the vessel wall
* Lack of toxicity
 
Polymers have been widely used in cardiovascular devices and are now primarily used as delivery vehicles for drug coatings. Polymers used for bioabsorbable stents are Poly-L-Lactic acid(PLLA), polyglycolic acid(PGA),Poly(D,L-lactide/glycolide) copolymer(PDLA) and polycaprolactone. The use of bioabsorbable polymer coating reduces the need for extended dual anti-platelet therapy and in turn late thrombotic events. Among the polymers, Poly-L-Lactic acid is widely used in medicine. It breaks down to lactic acid a natural metabolite in human body, which enters [[krebs Cycle]] and is metabolized to [[carbon dioxide]] and water. <ref> http://www.medscape.com/viewarticle/523241_2</ref> 
 
So far two bioabsorbable metals alloys have been proposed for this application: [[magnesium]] and [[iron]]. The factors that determine the biocompatibility of these alloys are their solubility and degradation products. Magnesium stents are made of 93% magnesium and 7% rare-earth-metals. Reasons for selecting magnesium include:
* It is an essential element in the body.
* The alloy induces rapid endothelialization.
* It has low thrombogenicity.
* It has a lower degradation time of 2-3 months.
* It has calcium antagonist and antiarrhythmic properties.
* Is not associated with any adverse reactions.<ref>http://onlinelibrary.wiley.com/doi/10.1002/ccd.20727/abstract;jsessionid=8D3133482E4FE43C7025F17E0655A06F.d03t01?userIsAuthenticated=false&deniedAccessCustomisedMessage=</ref>
 
The following is the list of some of the bioabsorbable stents that are currently under trials.<ref> http://circinterventions.ahajournals.org/content/2/3/255.full</ref>


==Types==
{|border="1" style="text-align:center"
{|border="1" style="text-align:center"
|-
|-
|'''Company'''||'''Polymer'''||'''Features'''
|'''Stent'''||'''Strut Material'''||'''Coating material'''||'''Design'''||'''Absorption products'''||'''Drug'''
|-
|Igaki-Tamai||Poly-L-Lactic acid||Nil||Zig-Zag helical that coils with straight bridges||Lactic acid, CO2 and H2O||Nil
|-
|-
|Igaki Medicals||Poly-L-Lactic acid||Contains no drug, self expanding
|REVA ||Poly(DTE carbonate) with Iodine on the backbone||Nil||Slide and lock design||Amino acids, ethanol and CO2|| [[Paclitaxel]]
|-
|-
|REVA Medical||Poly(DTE carbonate) with Iodine on the backbone||Slide and lock design, [[paclitaxel]] drug eluting stent
|Biotronic Mg-Alloy stent||Magnesium-alloy||Nil||Sinusoidal in-phase hoops linked by straight bridges||Not applicable||Nil
|-
|-
|Biotronic||Magnesium-alloy||[[Pimecrolimus]] drug eluting stent,Balloon expanding
|Abbott's BVS stent||Poly-L-Lactic acid||Poly-D,L-lactide||Out of phase sinusoidal hoops with straight and direct links in cohort-A and in-phase hoops with straight links in cohort-B||Lactic acid,  CO2 and H2O||[[Everolimus]]
|-
|-
|Abbott Vascular||Poly-L-Lactic acid||[[Everolimus]] drug eluting stent,self expanding
|Bioabsorbable therapeutics||Polymer salicylate + linker||Salicylate + different linker||Tube with laser cut voids||Salicylate, CO2 and H2O||[[Sirolimus]]
|}
|}
==Supportive Trial Data==
* The Igaki-Tamai stent was one of the first bioabsorbable stents to be tested in clinical trials. In the preliminary in-man prospective non-randomized clinical trials that involved 50 patients, a 4 year follow up of all patients revealed a low complication rate with 1 in-hospital stent thrombosis causing Q-wave [[myocardial infarction]], 1 non-cardiac death, 18% repeat [[PCI]] and no surgical [[revascularization]]. This stent is no longer in development now.
* Bioabsorbable therapeutics and REVA medical are testing stents coated with [[sirolimus]] and [[paclitaxel]] respectively.<ref name="pmid12050336">{{cite journal |author=Morice MC, Serruys PW, Sousa JE, ''et al.'' |title=A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization |journal=N. Engl. J. Med. |volume=346 |issue=23 |pages=1773–80|year=2002 |month=June |pmid=12050336 |doi=10.1056/NEJMoa012843 |url=}}</ref>
* PROGRESS-AMS study  is a prospective multicenter non-randomized study that used the Magnesium-alloy stent and was conducted on 63 patients. The results of this study are 100% device and procedural success rate and the study met it's primary endpoint of MACE(major adverse cardiac events) of <30%. The immediate angiographic results were similar to those after deployment of other metallic stents. Although the stent was absorbed completely within 2 months radial support was lost much earlier so that there was an insufficient radial strength to counter negative remodeling forces after PCI. Consequently there was high restenosis rate at 4 months of almost 50% and target vessel revascularization at 1 year was 45%. There were no deaths, MIs or stent thromboses, and the stent was no longer detectable by IVUS. The high restenosis rate may raise concern about safety.<ref name="pmid17544767">{{cite journal |author=Erbel R, Di Mario C, Bartunek J, ''et al.'' |title=Temporary scaffolding of coronary arteries with bioabsorbable magnesium stents: a prospective, non-randomised multicentre trial |journal=Lancet |volume=369 |issue=9576 |pages=1869–75 |year=2007 |month=June |pmid=17544767 |doi=10.1016/S0140-6736(07)60853-8 |url=}}</ref>
* The ABSORB trial involving Abbott's drug eluting BVS stent was a prospective non-randomized two phase study on 131 patients. Key endpoints included assessments of safety - major adverse cardiovascular events(MACE) and treated-site thrombosis rates - at 30 days and 6,9,12,24 months with additional annual clinical follow up for up to 5 years. The first phase (cohort A) of the trial enrolled 30 patients and its 2 year results demonstrated the following key results:
** A 0% rate of stent thrombosis for all patients
** No new MACE between 6 months and 2 years. At 2 years the device demonstrated a MACE rate of 3.6% (1 patient)
** Bioabsorption of the stent at 2 years after implantation as confirmed by an assessment of the stent struts using optical coherence tomography ([[OCT]])
** Restoration of vasomotion (ability of the blood vessel to contract and expand)
** Reduction in plaque area in treated arteries, as confirmed by [[IVUS]] and virtual histology
The second phase (cohort B) of the trial enrolled 101 patients and incorporated device enhancements designed to improve deliverability and vessel support. 30 day results demonstrated no cases of blood clots, no need for repeat procedures and a very low rate of MACE. At 1 year MACE was 6.9% with no reports of [[thrombosis]]. <ref name="pmid18342684">{{cite journal |author=Ormiston JA, Serruys PW, Regar E, ''et al.'' |title=A bioabsorbable everolimus-eluting coronary stent system for patients with single de-novo coronary artery lesions (ABSORB): a prospective open-label trial |journal=Lancet |volume=371 |issue=9616 |pages=899–907 |year=2008 |month=March |pmid=18342684 |doi=10.1016/S0140-6736(08)60415-8 |url=}}</ref> <ref name="pmid19286089">{{cite journal |author=Serruys PW, Ormiston JA, Onuma Y, ''et al.'' |title=A bioabsorbable everolimus-eluting coronary stent system (ABSORB): 2-year outcomes and results from multiple imaging methods |journal=Lancet |volume=373 |issue=9667 |pages=897–910 |year=2009 |month=March |pmid=19286089 |doi=10.1016/S0140-6736(09)60325-1 |url=}}</ref>
* In the EVOLVE trial experts compared 2 bioabsorbable polymer SYNERGY stents - one deliverig full dose of [[everolimus]] and one delivering half dose of the drug with the durable PROMUS ELEMENT metal stent delivering full dose of the drug in 291 patients. The angiographic outcomes of the study suggested that it may be possible to achieve at least comparable efficacy with a lower dose of everolimus than is used in commercially available everolimus-eluting stents. At 1 year the target lesion failure (TLF) in both the study arms were not statistically different (4.4%,4.2% and 5.1% for the full dose SYNERGY, half dose SYNERGY and PROMUS stents, respectively. TLF was defined as target-vessel-related cardiac death, target-vessel-related [[MI]], or ischemia-driven target lesion revascularization. Follow-up at 1 year demonstrated no cardiac related deaths or Q wave [[MI]] or stent thrombosis in any of the stent groups.<ref>  Meredith I, et al "Primary endpoint results of the EVOLVE trial: a randomized evaluation of a novel bioabsorbable polymer-coated, everolimus-eluting coronary stent" J Am Coll Cardiol 2012; DOI:
10.1016/j.jacc.2011.12.016 </ref> <ref name="pmid22341736">{{cite journal |author=Meredith IT, Verheye S, Dubois CL, ''et al.'' |title=Primary Endpoint Results of the EVOLVE Trial: A Randomized Evaluation of a Novel Bioabsorbable Polymer-Coated, Everolimus-Eluting Coronary Stent |journal=J. Am. Coll. Cardiol.|volume=59 |issue=15 |pages=1362–70 |year=2012 |month=April |pmid=22341736 |doi=10.1016/j.jacc.2011.12.016 |url=}}</ref>


==Advantages==
==Advantages==
The main advantages these Bioabsorbable stents can offer over the traditional bare metal [[stents]] are:
The potential advantages of the bioabsorbable stents over the traditional bare metal [[stents]] include:
* No late stent [[thrombosis]] - the stent being absorbed completely leaves behind no stimulus to ignite a chronic inflammatory process and thus in turn reducing the rate of late stent thrombosis which is a major concern of the traditional stents.
* Reduced late stent [[thrombosis]]: The stent being absorbed completely leaves behind no stimulus to ignite a chronic inflammatory process and thus in turn reducing the rate of late stent thrombosis which is a major concern of the traditional stents
* Short duration of post-stenting use of dual anti-platelet drugs.
* Short duration of post-stenting use of dual anti-platelet drugs
* Obviates metal implants in vessels, leaves only healed natural vessel
* Absence of metal implants in vessels, leaves only healed natural vessel
* Facilitates reintervention ([[PCI]] and [[CABG]])
* Improved lesion imaging with [[CT]] and [[MRI]] unlike their bare metal counterparts
* Prevents the constrictive vascular remodeling postdilatation due to the scaffolding effect of the stent and after being absorbed completely allows late expansive luminal and vessel remodeling.
* Easier reintervention ([[PCI]] and [[CABG]])<ref>http://www.theheart.org/documents/satellite_programs/intervcardiology/842901/transcript.pdf</ref>
* Increased drug loading capabilities that will enable chronic drug release strategies.
* Prevention of postdilatation constrictive vascular remodeling due to the scaffolding effect of the stent
* In the long run, eliminates mechanical stent deformity and strut fractures
* Late expansive luminal and vessel remodeling after the test is completely absorbed
* Can be used in peripheral arteries like the tibial artery,femoral artery etc.
* Increased drug loading capabilities that will enable chronic drug release strategies
* Elimination of the mechanical stent deformity and strut fractures
 
==Limitations==
The following are the limitations of these disappearing stents:
* Lower mechanical strength compared to their metallic counterparts, which can result in early recoil post implantation
* Significant local inflammation
* Impaired accurate positioning due to their radiolucent nature
* Limited mechanical performance and a recoil rate of approximately 20%, which requires thick struts impeding their delivery capabilities, especially in small vessels
* Limited use in calcified lesions due to their lack of mechanical strength<ref>http://www.theheart.org/article/1144463.do</ref>
 
==Future Applications==
The probable future applications of the bioabsorbable stents are:
* Possible use in peripheral arteries such as the [[femoral artery|femoral]] or [[tibial artery|tibial]] arteries
* Possible use of polymer stents as vehicles that transfer [[genes]] that code key regulatory pathways inside the cells of the arterial wall
* Possible use in pediatric [[congenital heart disease]]s such as[[pulmonary artery stenosis]]<ref name="pmid16206223">{{cite journal |author=Zartner P, Cesnjevar R, Singer H, Weyand M |title=First successful implantation of a biodegradable metal stent into the left pulmonary artery of a preterm baby |journal=Catheter Cardiovasc Interv |volume=66 |issue=4 |pages=590–4|year=2005 |month=December |pmid=16206223 |doi=10.1002/ccd.20520 |url=}}</ref>


==References==
==References==
{{reflist|2}}
{{reflist|2}}
{{WH}}
{{WS}}
[[CME Category::Cardiology]]


[[Category:Cardiac surgery]]
[[Category:Cardiac surgery]]
[[Category:cardiology]]
[[Category:Cardiology]]
[[Category:Surgery]]
[[Category:Surgery]]
{{WH}}
{{WS}}

Latest revision as of 05:17, 15 March 2016

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Raviteja Guddeti, M.B.B.S. [2]

Overview

Bioabsorbable stents, also known as the disappearing stents, are a promising new discovery in the field of interventional cardiology. They have been an interesting field of research over the past decade and half. As the name suggests they get absorbed completely over a period of time after their work is done. Percutaneous coronary intervention (PCI) using bioabsorbable stents has created special interest because the mechanical support for the healing artery is required only for a brief period of time, and also the presence of a bare metallic prosthesis has potential disadvantages beyond the first few months.[1] [2]

Classification

Bioabsorbable stents can be broadly classified into two types: polymeric and metallic types. The key features to be considered while selecting a polymer or an alloy for a bioabsorbable stent are:

  • Strength in order to avoid potential immediate recoil
  • Rate of degradation and corrosion
  • Biocompatibility with the vessel wall
  • Lack of toxicity

Polymers have been widely used in cardiovascular devices and are now primarily used as delivery vehicles for drug coatings. Polymers used for bioabsorbable stents are Poly-L-Lactic acid(PLLA), polyglycolic acid(PGA),Poly(D,L-lactide/glycolide) copolymer(PDLA) and polycaprolactone. The use of bioabsorbable polymer coating reduces the need for extended dual anti-platelet therapy and in turn late thrombotic events. Among the polymers, Poly-L-Lactic acid is widely used in medicine. It breaks down to lactic acid a natural metabolite in human body, which enters krebs Cycle and is metabolized to carbon dioxide and water. [3]

So far two bioabsorbable metals alloys have been proposed for this application: magnesium and iron. The factors that determine the biocompatibility of these alloys are their solubility and degradation products. Magnesium stents are made of 93% magnesium and 7% rare-earth-metals. Reasons for selecting magnesium include:

  • It is an essential element in the body.
  • The alloy induces rapid endothelialization.
  • It has low thrombogenicity.
  • It has a lower degradation time of 2-3 months.
  • It has calcium antagonist and antiarrhythmic properties.
  • Is not associated with any adverse reactions.[4]

The following is the list of some of the bioabsorbable stents that are currently under trials.[5]

Stent Strut Material Coating material Design Absorption products Drug
Igaki-Tamai Poly-L-Lactic acid Nil Zig-Zag helical that coils with straight bridges Lactic acid, CO2 and H2O Nil
REVA Poly(DTE carbonate) with Iodine on the backbone Nil Slide and lock design Amino acids, ethanol and CO2 Paclitaxel
Biotronic Mg-Alloy stent Magnesium-alloy Nil Sinusoidal in-phase hoops linked by straight bridges Not applicable Nil
Abbott's BVS stent Poly-L-Lactic acid Poly-D,L-lactide Out of phase sinusoidal hoops with straight and direct links in cohort-A and in-phase hoops with straight links in cohort-B Lactic acid, CO2 and H2O Everolimus
Bioabsorbable therapeutics Polymer salicylate + linker Salicylate + different linker Tube with laser cut voids Salicylate, CO2 and H2O Sirolimus

Supportive Trial Data

  • The Igaki-Tamai stent was one of the first bioabsorbable stents to be tested in clinical trials. In the preliminary in-man prospective non-randomized clinical trials that involved 50 patients, a 4 year follow up of all patients revealed a low complication rate with 1 in-hospital stent thrombosis causing Q-wave myocardial infarction, 1 non-cardiac death, 18% repeat PCI and no surgical revascularization. This stent is no longer in development now.
  • Bioabsorbable therapeutics and REVA medical are testing stents coated with sirolimus and paclitaxel respectively.[6]
  • PROGRESS-AMS study is a prospective multicenter non-randomized study that used the Magnesium-alloy stent and was conducted on 63 patients. The results of this study are 100% device and procedural success rate and the study met it's primary endpoint of MACE(major adverse cardiac events) of <30%. The immediate angiographic results were similar to those after deployment of other metallic stents. Although the stent was absorbed completely within 2 months radial support was lost much earlier so that there was an insufficient radial strength to counter negative remodeling forces after PCI. Consequently there was high restenosis rate at 4 months of almost 50% and target vessel revascularization at 1 year was 45%. There were no deaths, MIs or stent thromboses, and the stent was no longer detectable by IVUS. The high restenosis rate may raise concern about safety.[7]
  • The ABSORB trial involving Abbott's drug eluting BVS stent was a prospective non-randomized two phase study on 131 patients. Key endpoints included assessments of safety - major adverse cardiovascular events(MACE) and treated-site thrombosis rates - at 30 days and 6,9,12,24 months with additional annual clinical follow up for up to 5 years. The first phase (cohort A) of the trial enrolled 30 patients and its 2 year results demonstrated the following key results:
    • A 0% rate of stent thrombosis for all patients
    • No new MACE between 6 months and 2 years. At 2 years the device demonstrated a MACE rate of 3.6% (1 patient)
    • Bioabsorption of the stent at 2 years after implantation as confirmed by an assessment of the stent struts using optical coherence tomography (OCT)
    • Restoration of vasomotion (ability of the blood vessel to contract and expand)
    • Reduction in plaque area in treated arteries, as confirmed by IVUS and virtual histology

The second phase (cohort B) of the trial enrolled 101 patients and incorporated device enhancements designed to improve deliverability and vessel support. 30 day results demonstrated no cases of blood clots, no need for repeat procedures and a very low rate of MACE. At 1 year MACE was 6.9% with no reports of thrombosis. [8] [9]

  • In the EVOLVE trial experts compared 2 bioabsorbable polymer SYNERGY stents - one deliverig full dose of everolimus and one delivering half dose of the drug with the durable PROMUS ELEMENT metal stent delivering full dose of the drug in 291 patients. The angiographic outcomes of the study suggested that it may be possible to achieve at least comparable efficacy with a lower dose of everolimus than is used in commercially available everolimus-eluting stents. At 1 year the target lesion failure (TLF) in both the study arms were not statistically different (4.4%,4.2% and 5.1% for the full dose SYNERGY, half dose SYNERGY and PROMUS stents, respectively. TLF was defined as target-vessel-related cardiac death, target-vessel-related MI, or ischemia-driven target lesion revascularization. Follow-up at 1 year demonstrated no cardiac related deaths or Q wave MI or stent thrombosis in any of the stent groups.[10] [11]

Advantages

The potential advantages of the bioabsorbable stents over the traditional bare metal stents include:

  • Reduced late stent thrombosis: The stent being absorbed completely leaves behind no stimulus to ignite a chronic inflammatory process and thus in turn reducing the rate of late stent thrombosis which is a major concern of the traditional stents
  • Short duration of post-stenting use of dual anti-platelet drugs
  • Absence of metal implants in vessels, leaves only healed natural vessel
  • Improved lesion imaging with CT and MRI unlike their bare metal counterparts
  • Easier reintervention (PCI and CABG)[12]
  • Prevention of postdilatation constrictive vascular remodeling due to the scaffolding effect of the stent
  • Late expansive luminal and vessel remodeling after the test is completely absorbed
  • Increased drug loading capabilities that will enable chronic drug release strategies
  • Elimination of the mechanical stent deformity and strut fractures

Limitations

The following are the limitations of these disappearing stents:

  • Lower mechanical strength compared to their metallic counterparts, which can result in early recoil post implantation
  • Significant local inflammation
  • Impaired accurate positioning due to their radiolucent nature
  • Limited mechanical performance and a recoil rate of approximately 20%, which requires thick struts impeding their delivery capabilities, especially in small vessels
  • Limited use in calcified lesions due to their lack of mechanical strength[13]

Future Applications

The probable future applications of the bioabsorbable stents are:

References

  1. http://circinterventions.ahajournals.org/content/2/3/255.full
  2. Waksman R (2006). "Biodegradable stents: they do their job and disappear". J Invasive Cardiol. 18 (2): 70–4. PMID 16446520. Unknown parameter |month= ignored (help)
  3. http://www.medscape.com/viewarticle/523241_2
  4. http://onlinelibrary.wiley.com/doi/10.1002/ccd.20727/abstract;jsessionid=8D3133482E4FE43C7025F17E0655A06F.d03t01?userIsAuthenticated=false&deniedAccessCustomisedMessage=
  5. http://circinterventions.ahajournals.org/content/2/3/255.full
  6. Morice MC, Serruys PW, Sousa JE; et al. (2002). "A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization". N. Engl. J. Med. 346 (23): 1773–80. doi:10.1056/NEJMoa012843. PMID 12050336. Unknown parameter |month= ignored (help)
  7. Erbel R, Di Mario C, Bartunek J; et al. (2007). "Temporary scaffolding of coronary arteries with bioabsorbable magnesium stents: a prospective, non-randomised multicentre trial". Lancet. 369 (9576): 1869–75. doi:10.1016/S0140-6736(07)60853-8. PMID 17544767. Unknown parameter |month= ignored (help)
  8. Ormiston JA, Serruys PW, Regar E; et al. (2008). "A bioabsorbable everolimus-eluting coronary stent system for patients with single de-novo coronary artery lesions (ABSORB): a prospective open-label trial". Lancet. 371 (9616): 899–907. doi:10.1016/S0140-6736(08)60415-8. PMID 18342684. Unknown parameter |month= ignored (help)
  9. Serruys PW, Ormiston JA, Onuma Y; et al. (2009). "A bioabsorbable everolimus-eluting coronary stent system (ABSORB): 2-year outcomes and results from multiple imaging methods". Lancet. 373 (9667): 897–910. doi:10.1016/S0140-6736(09)60325-1. PMID 19286089. Unknown parameter |month= ignored (help)
  10. Meredith I, et al "Primary endpoint results of the EVOLVE trial: a randomized evaluation of a novel bioabsorbable polymer-coated, everolimus-eluting coronary stent" J Am Coll Cardiol 2012; DOI: 10.1016/j.jacc.2011.12.016
  11. Meredith IT, Verheye S, Dubois CL; et al. (2012). "Primary Endpoint Results of the EVOLVE Trial: A Randomized Evaluation of a Novel Bioabsorbable Polymer-Coated, Everolimus-Eluting Coronary Stent". J. Am. Coll. Cardiol. 59 (15): 1362–70. doi:10.1016/j.jacc.2011.12.016. PMID 22341736. Unknown parameter |month= ignored (help)
  12. http://www.theheart.org/documents/satellite_programs/intervcardiology/842901/transcript.pdf
  13. http://www.theheart.org/article/1144463.do
  14. Zartner P, Cesnjevar R, Singer H, Weyand M (2005). "First successful implantation of a biodegradable metal stent into the left pulmonary artery of a preterm baby". Catheter Cardiovasc Interv. 66 (4): 590–4. doi:10.1002/ccd.20520. PMID 16206223. Unknown parameter |month= ignored (help)

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