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Cost effectiveness of radial vs. femoral artery approach to outpatient cardiac catheterization
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Abstracts / Cardiovascular Revascularization Medicine 8 (2007) 116 – 154
of completely absorbable but biocompatible polymers are expected to minimize these risks Objective: To evaluate a new potentially innately anti-inflammatory, salicylate-based bioabsorbable polymer eluting a high dose of sirolimus with slow-release profile, in a clinically relevant animal model. Methods: Three drug-eluting polymer-coated stent types were implanted in pig coronary arteries using QCA to optimize stent apposition: (1) metal stents coated with salicylate polymer cross-linked by adipic acid polyanhydride ester containing sirolimus (PAE); (2) metal stents coated with polylactic acid containing sirolimus (PLA); and (3) Cypher stents. The dose density of sirolimus for PAE and PLA was 8.3 Ag/mm of stent length, with in vitro elution studies demonstrating a gradual elution over 30 days. Animals were terminated at 1 month for angiographic restudy and complete histopathologic and histomorphometric analyses. Results: At 1 month, PAE had similar intimal thickness compared to PLA and Cypher groups (0.16 mmF0.07 vs. 0.16 mmF0.10 and 0.15 mmF0.10 respectively; P=.126). Histological % stenosis was 22F7% for PAE vs. 26F11% for PLA and 31F13% for Cypher groups, respectively ( P=.992). The PAE group showed a mild inflammatory cell reaction similar to the PLA and Cypher groups. Conclusion: This study showed favorable vascular compatibility and efficacy of a novel salicylic acid/adipic acid biodegradable polymer eluting sirolimus, in a clinically relevant animal model. Ongoing research is directed towards further investigation of the potential innate anti-inflammatory nature of salicylic acid polymers and development of completely bioabsorbable stents from this interesting class of polymer materials.
Table 1 Numbers of MNGC on strut surfaces as a function of time.
(overlap) and distal stent regions; longitudinally bisected stented arteries were examined across the entire surface with SEM. Results: Comparable vascular responses were observed with all the three stent types in the first 10 days. Mild to moderate numbers of leukocytes were adherent to struts at Day 1, but no giant cell formation was observed. Between 2 and 4 days, MNGC were observed forming on struts but not on the surface of the artery (Fig. 1). At 4 days, a substantial portion (N50%) of the strut surfaces were covered by MNGC. It was often observed that where the endothelium was incomplete, the strut surface was occupied by MNGC. The peak time point for strut adherent MNGC was 4 days (Table 1). By 10 days, the surface of all three stent types was largely covered by endothelium. Strut-associated MNGC persisted out to 6 months, but from 10 to 20 days they were covered by an endothelialized fibrocellular neointima. Conclusions: Multinucleate giant cells may act as a surrogate endothelium prior to complete stent strut endothelial cell coverage. The type of stent surface does not seem to impact MNGC formation.
doi:10.1016/j.carrev.2007.03.129
doi:10.1016/j.carrev.2007.03.130
Multinucleate giant cells form an early surrogate endothelium on bare metal and drug-coated stent struts in swine coronary arteries PS Seifert, B Huibregtse, B Poff Boston Scientific Corporation, Natick, MA, USA
Cost effectiveness of radial vs. femoral artery approach to outpatient cardiac catheterization O Roussanov, G Estacio, J Hill, SJ Wilson, K Henley, B Dogan, N Jarmukli Salem Veterans Affairs Medical Center, Salem, VA, USA
Background: Multinucleate giant cells (MNGC) are found in association with biomaterial surfaces and chronic inflammatory states. It is thus a novel observation that they are found on stent strut surfaces within days of implantation in swine coronary arteries. Methods: Overlapping stents (bare metal Express, Taxus Express, and Cypher BxVelocity) from swine coronary arteries were examined by light microscopy (LM) and scanning electron microscopy (SEM) at 1, 2, 4, 10, 20, 30 days, and 6 months. LM sections were taken at proximal, middle
Background: In recent years, radial artery approach to diagnostic cardiac catheterization has become increasingly popular due to shorter procedural and recovery times, greater patient comfort and less procedural complications in experienced hands. Methods: A comparative cost analysis between patients who had radial or femoral (with and without closure device) outpatient diagnostic cardiac catheterization was performed in a Veterans Affairs Medical Center. Patients with prior bypass surgery and those undergoing
Multinucleate giant cells per section Day
Express (n)
Taxus (n)
2 4 10 20
0.7F1.4 5.5F4.4 2.5F3.1 0.1F0.5
0.2F0.5 5.8F5.5 2.8F4.9 0.9F2.2
(30) (30) (36) (33)
(30) (33) (30) (33)
Fig. 1. Left: Day 2 specimen demonstrating giant cell formation. Right: Histological view of a 2-day specimen showing a MNGC adherent to a strut.
Abstracts / Cardiovascular Revascularization Medicine 8 (2007) 116 – 154 concurrent right heart catheterization, peripheral angiogram, or vascular intervention were excluded. Results: Radial (R), femoral (F) and femoral with a closure device (F+C), such as Angioseal or Perclose, approaches were used in 39, 45, and 33 consecutive cases, respectively, at the discretion of the operator. Although the study was not designed to evaluate clinical outcomes, complication rates, including radial spasm, were zero in all groups. Group R had a higher access equipment cost of $93.3 vs. $40.5 in Group F (due to use of hydrophilic sheaths in the former), but lower catheter cost ($18.4F12.8 vs. $30.0F9.5, Pb.001) than Group F (with an average of 1.9 catheter per radial approach procedure), and lower contrast cost of $21.1F7.5 vs. $29.2F18.2 in Group F and $31.6F20.9 in Group F+C. There was a lower postprocedure recovery cost of $185.3F38.4 in Group R compared to $352.3F45.9 in Group F ( Pb.001) with a median recovery time of 2 and 4 h, respectively. Total variable procedural cost, which includes approach-dependent equipment and recovery room stay, was significantly lower in the radial group than in the femoral group ($342.8F51.7 vs. $453.1F50, Pb.001). Recovery cost savings in the femoral with closure device group were outweighed by the cost of the closure device itself bringing a total variable cost to $558.5F76.2 ( Pb.001 compared to Groups R and F). Conclusion: In experienced hands and in an outpatient population without prior bypass surgery the radial artery approach to diagnostic cardiac catheterization is clearly more cost effective than the femoral approach. doi:10.1016/j.carrev.2007.03.131
A novel method for intracoronary delivery of mesenchymal stem cells following myocardial infarct in pigs diminishes the risk of reduced reperfusion due to microvascular plugging S Epsteina, C Harrisa, T Freymana, D Hamamdzicb, S Hashemib, R Wilenskyb a Boston Scientific Corporation, Natick, MA, USA b University of Pennsylvania, Philadelphia, PA, USA Background: Clinical investigations of local delivery of cell therapies to improve outcomes following AMI are ongoing. Commonly, the guide-wire lumen of off-the-shelf angioplasty catheters is used to infuse cells into the infarct-related artery. The dose is delivered by repeating a procedure during which blood flow is stopped by balloon inflation, the cell suspension infused (typically 1 ml/min) and tissue reperfused by deflating the balloon. Previous studies have reported low delivery efficiencies and, with mesenchymal stem cells (MSCs), microembolization resulting in reduced
133
myocardial perfusion. In a porcine model of AMI, we investigated how higher-flow rate, bolus infusion influenced cell retention, and embolization compared to the above-described clinical protocol. Methods: MSCs were isolated from porcine bone marrow, expanded in culture to passage 3 and labeled with iron-fluorescent microspheres (Bangs Labs). Following 1 h of balloon-induced ischemia in the proximal LAD, animals were reperfused and allogeneic MSCs infused distal to the site of infarction using balloon catheters. All animals received infusions totaling 40 million MSCs in 10 ml of saline during balloon occlusion to stop blood flow. Ten animals were assigned to the maverick control group in which the cells were infused over the course of five infusions (1 ml/ min) with 2-min deflation and reperfusion times in between. Eight animals were assigned to the high flow rate prototype delivery arm (60 ml/min) and six animals were assigned to the low flow rate delivery arm (20 ml/min). Animals in the prototype groups received the cell dose as a single bolus injection. TIMI scores were assessed following ischemia/ reperfusion and cell delivery and prior to 14-day sacrifice. Following necropsy, the excised heart was imaged in a 5.7-T MRI unit to assess cell distribution via the iron-containing microspheres. Cell engraftment, in normal and infarcted myocardium, was quantified via the characteristic fluorescence of the microspheres following isolation of the microspheres using alkaline digestion and magnetic separation techniques. Results: MSC engraftment in the infarct zone at 14 days was similar across all groups ( PN.05). The mean value was 7.4 million cells per gram of infarct. MRI imaging and quantification revealed nearly all of the engrafted cells were confined to the infarct zone. Engraftment in the control arm was artificially increased by one animal in which cell infusion resulted in complete LAD occlusion and trapping of the entire cell dose within this vessel. This was confirmed by MRI imaging and is reflected in the higher standard deviation for this group compared to the two prototype groups (63% vs. 21% and 36%, respectively). The number of animals maintaining normal flow (TIMI=3) following cell delivery was markedly lower in the control arm (20%) compared to the high (63%) and the low flow rate (67%) bolus infusion groups. Early death (within 24 h of MI and cell delivery) was more common in the control arm (60%) than in the bolus infusion arms (14%). Independent of delivery group, early death occurred in 54% of animals with low myocardial perfusion following cell delivery (TIMI b3) while occurring in only 9% of those with normal perfusion (TIMI=3). Conclusions: Even with similar levels of engraftment, bolus delivery of stem cells markedly reduced risk of death and low myocardial perfusion secondary to microvascular plugging by stem cells. doi:10.1016/j.carrev.2007.03.132
Abstracts / Cardiovascular Revascularization Medicine 8 (2007) 116 – 154
of completely absorbable but biocompatible polymers are expected to minimize these risks Objective: To evaluate a new potentially innately anti-inflammatory, salicylate-based bioabsorbable polymer eluting a high dose of sirolimus with slow-release profile, in a clinically relevant animal model. Methods: Three drug-eluting polymer-coated stent types were implanted in pig coronary arteries using QCA to optimize stent apposition: (1) metal stents coated with salicylate polymer cross-linked by adipic acid polyanhydride ester containing sirolimus (PAE); (2) metal stents coated with polylactic acid containing sirolimus (PLA); and (3) Cypher stents. The dose density of sirolimus for PAE and PLA was 8.3 Ag/mm of stent length, with in vitro elution studies demonstrating a gradual elution over 30 days. Animals were terminated at 1 month for angiographic restudy and complete histopathologic and histomorphometric analyses. Results: At 1 month, PAE had similar intimal thickness compared to PLA and Cypher groups (0.16 mmF0.07 vs. 0.16 mmF0.10 and 0.15 mmF0.10 respectively; P=.126). Histological % stenosis was 22F7% for PAE vs. 26F11% for PLA and 31F13% for Cypher groups, respectively ( P=.992). The PAE group showed a mild inflammatory cell reaction similar to the PLA and Cypher groups. Conclusion: This study showed favorable vascular compatibility and efficacy of a novel salicylic acid/adipic acid biodegradable polymer eluting sirolimus, in a clinically relevant animal model. Ongoing research is directed towards further investigation of the potential innate anti-inflammatory nature of salicylic acid polymers and development of completely bioabsorbable stents from this interesting class of polymer materials.
Table 1 Numbers of MNGC on strut surfaces as a function of time.
(overlap) and distal stent regions; longitudinally bisected stented arteries were examined across the entire surface with SEM. Results: Comparable vascular responses were observed with all the three stent types in the first 10 days. Mild to moderate numbers of leukocytes were adherent to struts at Day 1, but no giant cell formation was observed. Between 2 and 4 days, MNGC were observed forming on struts but not on the surface of the artery (Fig. 1). At 4 days, a substantial portion (N50%) of the strut surfaces were covered by MNGC. It was often observed that where the endothelium was incomplete, the strut surface was occupied by MNGC. The peak time point for strut adherent MNGC was 4 days (Table 1). By 10 days, the surface of all three stent types was largely covered by endothelium. Strut-associated MNGC persisted out to 6 months, but from 10 to 20 days they were covered by an endothelialized fibrocellular neointima. Conclusions: Multinucleate giant cells may act as a surrogate endothelium prior to complete stent strut endothelial cell coverage. The type of stent surface does not seem to impact MNGC formation.
doi:10.1016/j.carrev.2007.03.129
doi:10.1016/j.carrev.2007.03.130
Multinucleate giant cells form an early surrogate endothelium on bare metal and drug-coated stent struts in swine coronary arteries PS Seifert, B Huibregtse, B Poff Boston Scientific Corporation, Natick, MA, USA
Cost effectiveness of radial vs. femoral artery approach to outpatient cardiac catheterization O Roussanov, G Estacio, J Hill, SJ Wilson, K Henley, B Dogan, N Jarmukli Salem Veterans Affairs Medical Center, Salem, VA, USA
Background: Multinucleate giant cells (MNGC) are found in association with biomaterial surfaces and chronic inflammatory states. It is thus a novel observation that they are found on stent strut surfaces within days of implantation in swine coronary arteries. Methods: Overlapping stents (bare metal Express, Taxus Express, and Cypher BxVelocity) from swine coronary arteries were examined by light microscopy (LM) and scanning electron microscopy (SEM) at 1, 2, 4, 10, 20, 30 days, and 6 months. LM sections were taken at proximal, middle
Background: In recent years, radial artery approach to diagnostic cardiac catheterization has become increasingly popular due to shorter procedural and recovery times, greater patient comfort and less procedural complications in experienced hands. Methods: A comparative cost analysis between patients who had radial or femoral (with and without closure device) outpatient diagnostic cardiac catheterization was performed in a Veterans Affairs Medical Center. Patients with prior bypass surgery and those undergoing
Multinucleate giant cells per section Day
Express (n)
Taxus (n)
2 4 10 20
0.7F1.4 5.5F4.4 2.5F3.1 0.1F0.5
0.2F0.5 5.8F5.5 2.8F4.9 0.9F2.2
(30) (30) (36) (33)
(30) (33) (30) (33)
Fig. 1. Left: Day 2 specimen demonstrating giant cell formation. Right: Histological view of a 2-day specimen showing a MNGC adherent to a strut.
Abstracts / Cardiovascular Revascularization Medicine 8 (2007) 116 – 154 concurrent right heart catheterization, peripheral angiogram, or vascular intervention were excluded. Results: Radial (R), femoral (F) and femoral with a closure device (F+C), such as Angioseal or Perclose, approaches were used in 39, 45, and 33 consecutive cases, respectively, at the discretion of the operator. Although the study was not designed to evaluate clinical outcomes, complication rates, including radial spasm, were zero in all groups. Group R had a higher access equipment cost of $93.3 vs. $40.5 in Group F (due to use of hydrophilic sheaths in the former), but lower catheter cost ($18.4F12.8 vs. $30.0F9.5, Pb.001) than Group F (with an average of 1.9 catheter per radial approach procedure), and lower contrast cost of $21.1F7.5 vs. $29.2F18.2 in Group F and $31.6F20.9 in Group F+C. There was a lower postprocedure recovery cost of $185.3F38.4 in Group R compared to $352.3F45.9 in Group F ( Pb.001) with a median recovery time of 2 and 4 h, respectively. Total variable procedural cost, which includes approach-dependent equipment and recovery room stay, was significantly lower in the radial group than in the femoral group ($342.8F51.7 vs. $453.1F50, Pb.001). Recovery cost savings in the femoral with closure device group were outweighed by the cost of the closure device itself bringing a total variable cost to $558.5F76.2 ( Pb.001 compared to Groups R and F). Conclusion: In experienced hands and in an outpatient population without prior bypass surgery the radial artery approach to diagnostic cardiac catheterization is clearly more cost effective than the femoral approach. doi:10.1016/j.carrev.2007.03.131
A novel method for intracoronary delivery of mesenchymal stem cells following myocardial infarct in pigs diminishes the risk of reduced reperfusion due to microvascular plugging S Epsteina, C Harrisa, T Freymana, D Hamamdzicb, S Hashemib, R Wilenskyb a Boston Scientific Corporation, Natick, MA, USA b University of Pennsylvania, Philadelphia, PA, USA Background: Clinical investigations of local delivery of cell therapies to improve outcomes following AMI are ongoing. Commonly, the guide-wire lumen of off-the-shelf angioplasty catheters is used to infuse cells into the infarct-related artery. The dose is delivered by repeating a procedure during which blood flow is stopped by balloon inflation, the cell suspension infused (typically 1 ml/min) and tissue reperfused by deflating the balloon. Previous studies have reported low delivery efficiencies and, with mesenchymal stem cells (MSCs), microembolization resulting in reduced
133
myocardial perfusion. In a porcine model of AMI, we investigated how higher-flow rate, bolus infusion influenced cell retention, and embolization compared to the above-described clinical protocol. Methods: MSCs were isolated from porcine bone marrow, expanded in culture to passage 3 and labeled with iron-fluorescent microspheres (Bangs Labs). Following 1 h of balloon-induced ischemia in the proximal LAD, animals were reperfused and allogeneic MSCs infused distal to the site of infarction using balloon catheters. All animals received infusions totaling 40 million MSCs in 10 ml of saline during balloon occlusion to stop blood flow. Ten animals were assigned to the maverick control group in which the cells were infused over the course of five infusions (1 ml/ min) with 2-min deflation and reperfusion times in between. Eight animals were assigned to the high flow rate prototype delivery arm (60 ml/min) and six animals were assigned to the low flow rate delivery arm (20 ml/min). Animals in the prototype groups received the cell dose as a single bolus injection. TIMI scores were assessed following ischemia/ reperfusion and cell delivery and prior to 14-day sacrifice. Following necropsy, the excised heart was imaged in a 5.7-T MRI unit to assess cell distribution via the iron-containing microspheres. Cell engraftment, in normal and infarcted myocardium, was quantified via the characteristic fluorescence of the microspheres following isolation of the microspheres using alkaline digestion and magnetic separation techniques. Results: MSC engraftment in the infarct zone at 14 days was similar across all groups ( PN.05). The mean value was 7.4 million cells per gram of infarct. MRI imaging and quantification revealed nearly all of the engrafted cells were confined to the infarct zone. Engraftment in the control arm was artificially increased by one animal in which cell infusion resulted in complete LAD occlusion and trapping of the entire cell dose within this vessel. This was confirmed by MRI imaging and is reflected in the higher standard deviation for this group compared to the two prototype groups (63% vs. 21% and 36%, respectively). The number of animals maintaining normal flow (TIMI=3) following cell delivery was markedly lower in the control arm (20%) compared to the high (63%) and the low flow rate (67%) bolus infusion groups. Early death (within 24 h of MI and cell delivery) was more common in the control arm (60%) than in the bolus infusion arms (14%). Independent of delivery group, early death occurred in 54% of animals with low myocardial perfusion following cell delivery (TIMI b3) while occurring in only 9% of those with normal perfusion (TIMI=3). Conclusions: Even with similar levels of engraftment, bolus delivery of stem cells markedly reduced risk of death and low myocardial perfusion secondary to microvascular plugging by stem cells. doi:10.1016/j.carrev.2007.03.132