Far infrared treatment on the arteriovenous fistula induces changes in sVCAM and sICAM in patients on hemodialysis.

INTRODUCTION: There is a substantial risk of developing stenosis and dysfunction in the arteriovenous fistula (AVF) in patients on hemodialysis (HD). Far infrared radiation (FIR) is a non-invasive local intervention with a potentially beneficial effect on AVF patency. The underlying mechanism is not clear. It was hypothesized that a single FIR treatment reduces factors of inflammation and promotes endothelial vasodilators in the AVF. METHODS: Forty HD patients with an AVF were included in an open-label intervention study. Patients were randomized to receive either FIR (FIR group) or no FIR (control group). Blood samples were drawn directly from the AVF and from a peripheral vein in the non-AVF arm before (T0) and 40 min after (T40) treatment during a HD session. The changes [median (interquartile range)] in circulating factors of inflammation, endothelial function and vasoreactivity during FIR were measured. RESULTS: In the AVF a single FIR treatment during dialysis resulted in a significantly diminished decrease in soluble vascular cell adhesion molecule, sVCAM [-31.6 (-54.3; 22.1) vs -89.9 (-121.6; -29.3), P = .005] and soluble intercellular adhesion molecule, sICAM [-24.2 (-43.5; 25.3) vs -49 (-79.9; -11.6), P = .02] compared with the control group. Other factors, such as interleukins, nitrite, nitrate and tumor necrosis factor 1, also declined during dialysis, but with no significant differences related to FIR in either the AVF or the non-AVF arm. CONCLUSION: A single FIR treatment attenuated the decrease in sVCAM and sICAM in the AVF compared with a control group during HD. Findings do not support the hypothesis of a vaso-protective effect of FIR. The long-term effects of FIR on the AVF are unknown.

Effects of far infrared therapy on arteriovenous fistulas in hemodialysis patients: a meta-analysis.

BACKGROUND: Far infrared (FIR) therapy may have a beneficial effect on maturity and function of arteriovenous fistulas (AVFs) in hemodialysis (HD) patients. Therefore, we performed this pooled analysis to assess the protective effects of FIR therapy in HD patients. METHODS: The randomized controlled trials (RCTs) and quasi-RCTs of FIR therapy for HD patients were searched from multiple databases. Relevant studies were screened according to the predefined inclusion criteria. The meta-analyses were performed using RevMan 5.2 software (The Cochrane Collaboration, Oxford, UK). RESULTS: Meta-analysis showed that FIR therapy could significantly increase the vascular access blood flow level (MD, 81.69 ml/min; 95% CI, 46.17-117.21; p < .001), AVFs diameter level (MD, 0.36 mm; 95% CI, 0.22-0.51; p < .001), and the primary AVFs patency (pooled risk ratio = 1.24; 95% CI, 1.12-1.37, p < .001). In addition, therapy with FIR ray radiation could decrease AVFs occlusion rates (pooled risk ratio = 0.20; 95% CI, 0.08-0.46; p < .001) and the level of needling pain (pooled risk ratio = 0.08; 95% CI, 0.06-0.10, p < .001). CONCLUSIONS: FIR therapy can reduce AVFs occlusion rates and needling pain level, while significantly improve the level of vascular access blood flow, AVFs diameter and the primary AVFs patency.

High dose-rate brachytherapy for the treatment of lower extremity in-stent restenosis.

OBJECTIVE: Historically, edge stenosis and late thrombosis limited the effectiveness of adjunctive endovascular brachytherapy (EVBT) for in-stent restenosis (ISR) after percutaneous transluminal angioplasty (PTA) and stenting. We evaluated an updated protocol of PTA and EVBT for ISR among patients with lower extremity occlusive disease. METHODS: This is a retrospective, single-center review of patients treated with PTA and EVBT for ISR in the iliac and femoropopliteal segments between 2004 and 2012. A dose of 20 Gy was given at a depth of 0.5 mm beyond the radius of the largest PTA balloon using iridium 192, with at least 2-cm-long margins of radiation coverage proximal and distal to the injured area. Stents were assessed for patency by duplex ultrasound imaging at 1, 3, 6, 9, 12, and 18 months and then yearly. The primary end point was freedom from ≥50% restenosis in the treated segment at 6 months, 1 year, and 2 years. Patency data were estimated using the Kaplan-Meier method. Secondary end points were early and late thrombotic occlusion. RESULTS: Among 42 consecutive cases in 35 patients of EVBT for ISR in common or external iliac (9 [20.8%]) and superficial femoral or popliteal (33 [76.7%]) arteries, or both, 21 patients (50%) had claudication, asymptomatic hemodynamically significant stenoses were identified on duplex ultrasound imaging in 16 (38.1%), and 4 (9.8%) had critical limb ischemia. Mean treated length was 23.5 ± 12.3 cm over a mean duration of 16.1 ± 9.6 minutes. There was one technical failure (2.3%). Median post-EVBT follow-up time was 682 days (range, 1-2262 days). There were two (4.9%) and five (11.9%) cases of early and late thrombotic occlusions, respectively. There was one death, believed to be secondary to acute coronary syndrome. Primary, assisted primary, and secondary patency in the entire cohort was 75.2%, 89.1%, and 89.1%, respectively, at 1 year and 63.7%, 80.6%, and 85.6%, respectively, at 2 years. CONCLUSIONS: This contemporary protocol of PTA and adjunctive EVBT for lower extremity ISR, which is updated from those used in prior trials and includes a surveillance strategy that identifies at-risk stents for reintervention before occlusion, may be a promising treatment for lower extremity ISR at institutions where a close collaboration between vascular surgeons and radiation oncologists is feasible.

An update of the effect of far infrared therapy on arteriovenous access in end-stage renal disease patients.

The life qualities of end-stage renal disease (ESRD) patients rely largely on adequate dialysis, and a well-functioning vascular access is indispensable for high quality hemodialysis. Despite the advancement of surgical skills and the optimal maintenance of arteriovenous fistula (AVF), malfunction of AVF is still frequently encountered and has great impact on the life of ESRD patients. Several medical, mechanical and genetic prognostic factors are documented to affect the patency of AVF and arteriovenous graft (AVG). Heme oxygenase-1 (HO-1) is one of the genetic factors reported to play a role in cardiovascular disease and the patency of vascular access. Far infrared (FIR), a novel therapeutic modality, can not only conduct heat energy to AVF but also stimulate the non-thermal reactions mediated by HO-1. The use of FIR therapy significantly enhances the primary patency rate and maturation of AVF with fewer unfavorable adverse effects, and also achieves higher post-angioplasty patency rate for AVG. The only limitation in proving the effectiveness of FIR therapy in enhancing patency of AVF is that all the studies were conducted in Chinese people in Taiwan and thus, there is a lack of evidence and experience in people of other ethnicities.

Post-angioplasty far infrared radiation therapy improves 1-year angioplasty-free hemodialysis access patency of recurrent obstructive lesions.

OBJECTIVE: To explore the role of far infrared (FIR) radiation therapy for hemodialysis (HD) access maintenance after percutaneous transluminal angioplasties (PTA). METHODS: This was a prospective observational study. Eligible patients were those who received repeated PTA with the last PTA successfully performed within 1 week before the study enrollments. Consecutively enrolled patients undergoing successful HD treatments after PTA were randomly assigned to the FIR-radiated group or control group without radiation. FIR-radiated therapy meaning 40-minute radiation at the major lesion site or anastomosed site three times a week was continued until an end-point defined as dysfunction-driven re-PTA or the study end was reached. RESULTS: Of 216 participants analyzed, including 97 with arteriovenous grafts (AVG) (49 FIR-radiated participants and 48 control participants) and 119 with arteriovenous fistulas (AVF) (69 FIR-radiated participants and 50 control participants), the FIR-radiated therapy compared with free-radiated usual therapy significantly enhanced PTA-unassisted patency at 1 year in the AVG subgroup (16.3% vs. 2.1%; p < .01), but not the AVF subgroup (25.0% vs. 18.4%; p = .50), and this accounted for the overall improved patency rates (21.4% vs. 10.3%; p = .02). CONCLUSIONS: This study suggests FIR-radiated therapy improves PTA-unassisted patency in patients with AVG who have undergone previous PTA.

High-dose preoperative fractionated radiotherapy does not affect the patency and healing of ePTFE vascular prosthesis after replacement of canine abdominal aorta and inferior vena cava.

BACKGROUND: Fractionated radiotherapy allows for the safe administration of larger doses without the development of immediate or late toxicity. The influence of preoperative fractionated radiotherapy on neointima formation for expanded polytetrafluoroethylene (ePTFE) graft has not been determined. METHODS: Twenty mongrel dogs were randomly divided into radiotherapy group (a total dose of 35 Gy) or control group (no radiation). The infrarenal abdominal aorta and inferior vena cava were replaced by ePTFE grafts at 3 months after irradiation in the radiotherapy group. Grafts were explanted at 4 weeks after surgery. Histopathological techniques were undertaken to evaluate graft neointima formation. The control group was managed the same as the radiotherapy group except for not receiving irradiation. RESULTS: Four grafts implanted into inferior vena cava in the irradiated group and three in the control group were found to be completely occluded. None of the grafts implanted into abdominal aorta were obstructed. In the case of the inferior vena cava graft, the thickness of the graft neointima did not differ significantly between the irradiated and control groups. However, for the abdominal aorta graft, the neointima thickness in the irradiated groups was significantly thinner than that in the control group. CONCLUSION: Preoperative fractionated radiotherapy affects vascular healing via suppressing the development of neointima formation in the abdominal aorta graft.

Cilostazol effectively reduces the decrease of flow volume in a thrombotic anastomosis model in a rat: a novel application of ultrasonography for evaluation.

The purpose of this study was to investigate the efficacy of cilostazol for prevention of thrombosis in microsurgical anastomosis. We used not only a patency test, but also ultrasonography to evaluate the blood flow volume (FV) more accurately and objectivity. In addition, we evaluated the accuracy and sensitivity of the patency test. Thrombogenic anastomoses were performed on rat external iliac arteries. Forty-six rats were randomly allocated into the following 5 experimental groups: negative control, without any surgery and medication; control, received distilled water orally; group A, received aspirin orally; group B, received cilostazol orally; and group C, received aspirin and cilostazol orally 3 hours before a thrombogenic artery anastomosis. The artery was evaluated by FV using ultrasonography and a patency test 10, 30, and 120 minutes after clamp removal. The FV in group C was significantly larger than the control group 30 minutes after clamp removal. The FVs in groups A, B, and C were significantly larger than the control group 120 minutes after clamp removal. The FV decreased in all groups with time. The patency rate between the control group and group C 120 minutes after clamp removal was significantly different. There were 8 false negatives in a total of 114 patency tests. The total accuracy and sensitivity of the patency test were 93.0% and 92.7%, respectively. Cilostazol plus aspirin therapy is recommended for reducing thrombosis and increasing FV without increasing the risk of bleeding during microsurgery. The patency test cannot evaluate the state of the anastomotic vessels accurately and objectively.

Excimer Laser Assisted Non-occlusive Anastomosis (ELANA). Our experience with a training model in vivo.

AIM: In this study the ELANA Technique has been reproduced in our experimental laboratory in order to verify its feasibility and reproducibility, the percentage of patent anastomosis in acute at different steps along the learning curve of the surgical team, specific problems related to the surgical technique. METHODS: In 20 rabbits New Zealand 4kg body weight the training model in vivo proposed by Tulleken and coworkers has been reproduced, realizing 40 ELANA anastomosis. The model consists in the realization of two different end-to-side anastomosis on the abdominal aorta of each experimental animal, assisted by a special designed suction/excimer laser catheter, then connected by an end-to-end suture. After a few hours the animals are sacrificed and the by-pass site withdrawn and examined in order to verify the percentage of patency in acute. RESULTS: In the first 5 animals (group A), the anastomosis were realized using a jugular vein graft and the procedure results successful in only 3 cases out of ten (30%). For the following experiments - groups B, C and D where an aorta artery graft was used, the percentage of arterial flap retrieval was respectively 50%, 60% and 80%. CONCLUSIONS: ELANA is a feasible fascinating microsurgical technique for the realization of high flow, non-occlusive anastomosis. The rate of success results progressively higher along the learning curve of the surgical team. In our opinion, before the application of the ELANA technique on humans, a period of propaedeutic training in vivo on laboratory animals is essential for the dedicated team.

Far-infrared therapy: a novel treatment to improve access blood flow and unassisted patency of arteriovenous fistula in hemodialysis patients.

Vascular access malfunction, usually presenting with an inadequate access flow (Qa), is the leading cause of morbidity and hospitalization in hemodialysis (HD) patients. Many methods of thermal therapy have been tried for improving Qa but with limited effects. This randomized trial was designed to evaluate the effect of far-infrared (FIR) therapy on access flow and patency of the native arteriovenous fistula (AVF). A total of 145 HD patients were enrolled with 73 in the control group and 72 in the FIR group. A WS TY101 FIR emitter was used for 40 min, and hemodynamic parameters were measured by the Transonic HD(02) monitor during HD. The Qa(1)/Qa(2) and Qa(3)/Qa(4) were defined as the Qa measured at the beginning/at 40 min later in the HD session before the initiation and at the end of the study, respectively. The incremental change of Qa in the single HD session with FIR therapy was significantly higher than that without FIR therapy (13.2 +/- 114.7 versus -33.4 +/- 132.3 ml/min; P = 0.021). In comparison with control subjects, patients who received FIR therapy for 1 yr had (1) a lower incidence (12.5 versus 30.1%; P < 0.01) and relative incidence (one episode per 67.7 versus one episode per 26.7 patient-months; P = 0.03) of AVF malfunction; (2) higher values of the following parameters, including Delta(Qa(4) - Qa(3)) (36.2 +/- 82.4 versus -12.7 +/- 153.6 ml/min; P = 0.027), Delta(Qa(3) - Qa(1)) (36.3 +/- 166.2 versus -51.7 +/- 283.1 ml/min; P = 0.035), Delta(Qa(4) - Qa(2)) (99.2 +/- 144.4 versus -47.5 +/- 244.5 ml/min; P < 0.001), and Delta(Qa(4) - Qa(2)) - Delta(Qa(3) - Qa(1)) (62.9 +/- 111.6 versus 4.1 +/- 184.5 ml/min; P = 0.032); and (3) a better unassisted patency of AVF (85.9 versus 67.6%; P < 0.01). In conclusion, FIR therapy, a noninvasive and convenient therapeutic modality, can improve Qa and survival of the AVF in HD patients through both its thermal and its nonthermal effects.

Intracoronary beta-irradiation prevents excessive in-stent neointimal proliferation in de novo lesions of patients with high plasma ACE levels. The BetAce randomized trial.

BACKGROUND: This study evaluated vascular brachytherapy (VBT) as a potent antiproliferative treatment to prevent in-stent restenosis (ISR) after coronary angioplasty of de novo lesions in patients carrying the D allele of the I/D polymorphism of the ACE gene and high ACE plasma levels (>34 U/l). METHODS AND MATERIALS: A prospective randomized trial was designed to detect a 30% improvement in the minimal lumen diameter (MLD) of the stenotic artery, as measured by quantitative coronary analysis (QCA), 6 months following VBT at the time of stented angioplasty. All patients were carriers of the D allele of the ACE gene, with plasma ACE levels >34 U/l. RESULTS: Thirty-one patients (33 stenoses) were allocated to stent implantation (control group) and 30 patients (31 stenoses) to VBT and stented angioplasty. After angioplasty, in-stent MLD was similar in the two groups. At 6 months in the control group, in-stent MLD had decreased to 1.74+/-0.8 versus 2.25+/-1.05 mm in the VBT group (P=.04). The mean in-stent diameter was 2.3+/-0.8 mm in the control group versus 2.9+/-1.05 mm after VBT (P=.02), and the restenosis rate was 37.5% versus 17.9%, respectively (P=.08). At 6 months, a higher need for target vessel revascularization (TVR) was observed in the control group: 35.5% versus 13.3% (P=.04). CONCLUSIONS: This randomized study confirms that patients with high plasma ACE concentrations are exposed to an increased risk for ISR after coronary stenting. The preventive use of VBT in these patients reduced neointimal formation by 65% such that the MLD at follow-up was increased by 29% compared with the control group.

Carotid artery revascularization through a radiated field.

OBJECTIVE: Extracranial carotid stenosis is a complication of external head and neck irradiation. The safety and durability of carotid artery revascularization through a radiated field has been debated. We describe the immediate and long-term results in a series of 27 consecutive patients who received treatment over 12 years. METHODS: From May 1990 to May 2002, 27 consecutive patients underwent 30 primary carotid artery revascularization procedures. All patients had received previous radiation therapy within a mean interval of 10 years (range, 1-26 years), with average radiation dose of 62 Gy (range, 50-70 Gy). Moderate to severe scarring of the skin or radiation fibrosis was present in three fourths of patients. Thirteen patients (48%) had undergone radical neck dissection, and 2 patients had a permanent tracheotomy. The indications for carotid surgery included high-grade (>70%) symptomatic stenosis in 18 patients (60%) and high-grade asymptomatic stenosis in 12 patients (40%). General anesthesia with systematic shunting was used in 18 patients (60%), and regional anesthesia with selective shunting was used in 12 patients (40%). Operations included standard carotid endarterectomy (n = 20), with patch angioplasty (n = 12) or direct closure (n = 8); carotid interposition bypass grafting (n = 7); and subclavian to carotid bypass grafting (n = 3). Primary closure of the surgical wound was performed in all procedures without any special muscular or skin flaps. All patients were followed up for a mean of 40 months (range, 3-99 months). RESULTS: There was one (3.3%) perioperative death, from massive intracerebral hemorrhage; and 1 patient had a transient ischemic attack. In-hospital complications included neck hematoma in 2 patients, which required surgical drainage in 1 patient. There was neither delayed wound healing nor infection. Twelve patients died during follow-up, of causes not related to treatment. None of the surviving patients had further stroke, and all remained asymptomatic. Follow-up duplex scans showed asymptomatic recurrent stenosis greater than 60% in 3 patients, 2 of whom with stenosis greater than 80% underwent repeat operation. Risk for recurrent stenosis greater than 60% at 18 months was 16.6%. Recurrent stenosis occurred in 2 of these patients after saphenous vein bypass, and in 1 patient after endarterectomy with vein patch angioplasty. CONCLUSION: The clinical results and sustained freedom from symptoms and stroke over 40-month follow-up suggests that carotid revascularization through a radiated field is a safe and durable procedure in patients at high surgical risk, despite a marked incidence of recurrent stenosis.

Randomized trial of 90Sr/90Y beta-radiation versus placebo control for treatment of in-stent restenosis.

BACKGROUND: After conventional treatment of in-stent restenosis, the incidence of recurrent clinical restenosis may approach 40%. We report the first multicenter, blinded, and randomized trial of intracoronary radiation with the use of a 90Sr/90Y beta-source for the treatment of in-stent restenosis. METHODS AND RESULTS: After successful catheter-based treatment of in-stent restenosis, 476 patients were randomly assigned to receive an intracoronary catheter containing either 90Sr/90Y (n=244) or placebo (n=232) sources. The prescribed dose 2 mm from the center of the source was 18.4 Gy for vessels between 2.70 and 3.35 mm in diameter and 23.0 Gy for vessels between 3.36 and 4.0 mm. The primary end point, ie, clinically driven target-vessel revascularization by 8 months, was observed in 56 (26.8%) of the patients assigned to placebo and 39 (17.0%) of the patients assigned to radiation (P=0.015). The incidence of the composite including death, myocardial infarction, and target-vessel revascularization was observed in 60 (28.7%) of the patients assigned to placebo and 44 (19.1%) of the patients assigned to radiation (P=0.024). Binary 8-month angiographic restenosis (> or =50% diameter stenosis) within the entire segment treated with radiation was reduced from 45.2% in the placebo-treated patients to 28.8% in the 90Sr/90Y-treated patients (P=0.001). Stent thromboses occurred in 1 patient assigned to placebo <24 hours after the procedure and in 1 patient assigned to 90Sr/90Y at day 244. CONCLUSIONS: The results of this study demonstrated that beta-radiation using 90Sr/90Y is both safe and effective for preventing recurrence in patients with in-stent restenosis.

Two-year angiographic follow-up of intracoronary Sr90 therapy for restenosis prevention after balloon angioplasty.

BACKGROUND: Postcoronary angioplasty vascular brachytherapy (VBT) has emerged as a successful intervention for restenosis prevention in some clinical scenarios. Longer-term follow-up after VBT in de novo nonstented lesions has not been reported. METHODS AND RESULTS: Thirty patients treated with post-percutaneous transluminal coronary angioplasty (PTCA) VBT with Sr90 underwent clinical and angiographic follow-up at 6 and 24 months. Specific vessel segment quantitative coronary angiographic analyses were performed to identify radiation edge effects. Nineteen patients who had not undergone index procedure stenting or target vessel revascularization (TVR) over the 2-year period were analyzed separately. Of the 30 patients, 3 underwent TVR by 6-month follow-up. An additional 4 patients required TVR between 6 and 24 months. In the total cohort of 26 patients undergoing angiographic follow-up at 6 and 24 months, an increase in minimal lumen diameter of the initial target segment was noted at 6 months compared with postprocedure analysis (2.31+/-0.48 versus 2.04+/-0.43 mm, P<0.05). At 24 months, this was no longer significant (2.19+/-0.61 mm). In the proximal segments of the entire cohort and the nonintervened subgroup, the principal late loss occurred over the first 6 months with no additional late loss at 2-year follow-up. The distal segments remained stable over the entire follow-up period. CONCLUSIONS: Although some late failures of post-PTCA VBT are seen between 6 and 24 months, most treated vessels remain stable with no late loss or additional luminal increase beyond the 6-month period. This suggests that late aneurysm formation and significant late edge restenosis are unlikely in VBT after PTCA of de novo lesions for up to 2 years.

Late vascular response to repeat stenting for in-stent restenosis with and without radiation: an intravascular ultrasound volumetric analysis.

BACKGROUND: Re-stenting of in-stent restenosis (ISR) improves acute angiographic results. Methods and Results- Volumetric intravascular ultrasound analysis was performed in 70 ISR lesions that received either placebo (n=36) or (192)Ir radiation (n=34). ISR lesions treated by re-stenting were divided into 3 groups: old stent not re-stented (A), old/new stent overlap (B), and new stent only (C). ISR lesions treated without re-stenting were categorized as D. In placebo patients, postintervention lumen volume index (LVI) was significantly greater in re-stented segments B and C than in non-re-stented segment A (P<0.05).At follow-up, however, LVI was similar in all 4 segments secondary to the increased intimal hyperplasia (IH) reaccumulation within the re-stented segments. In patients treated with (192)Ir radiation, LVI was maintained from baseline to follow-up only in non-re-stented segments A and D. Conversely, there was a significant decrease in LVI in re-stented segments B and C (P<0.05). Qualitatively, 79% of patients in the irradiated group had stent struts with undetectable neointimal versus only 27% in the placebo group (P<0.001). Coefficient of variation of IH reaccumulation was greater in re-stented segments of (192)Ir patients (B=57.3% and C=58.9%) than in re-stented segments in placebo patients (B=27.3% and C 26.8%) and non-re-stented segments in irradiated patients. CONCLUSIONS: Additional lumen gain from re-stenting ISR lesions is counteracted by exaggerated neointimal proliferation in placebo patients. Maximum effectiveness and safety of radiation can be achieved for ISR lesions when treated without re-stenting. Thus, regardless of supplementary intravascular brachytherapy, repeat stenting strategies provided little long-term advantage.

Peripheral vascular brachytherapy.

Ongoing advances in peripheral endovascular technology have been met with disappointing results because of restenosis within the treated vessel. In particular, stent balloon angioplasty of peripheral vessels has yet to achieve patency rates that approximate conventional treatment in the long term. Recent advances in stent, balloon, and wire construction include the incorporation of radioactive substances in an attempt to ameliorate the inflammatory response provoked by typical endovascular manipulation, a technique termed vascular brachytherapy. gamma- and beta-isotopes and external beam radiation target the very cell population whose activity results in the development of neointimal hyperplasia. Although most clinical research examining the efficacy of vascular brachytherapy has emerged from the coronary artery literature, the use of vascular brachytherapy also has been examined in the peripheral arterial tree and has shown promising results. Current data indicate that vascular brachytherapy is a safe and accessible adjunctive endovascular maneuver that may improve the short-term patency rate of peripheral endovascular applications. The effects on long-term patency rates remain indeterminate compared to conventional therapy.

Device selection in the treatment of in-stent restenosis with and without radiation (from the Gamma Radiation Trials).

In-stent restenosis (ISR) is a major limitation of coronary stenting and is associated with high recurrence rates after intervention with all available devices. Intracoronary gamma (gamma) radiation was proved to reduce the recurrence rate after conventional therapy. The purpose of this study was to compare the different devices utilized for the treatment of ISR with and without gamma radiation. To search for the optimal device for the treatment of ISR, 685 patients from the radiation trials for ISR who were randomized to either iridium-192 gamma radiation (559 patients) or placebo (126 patients) following intervention were evaluated. Devices used included balloon percutaneous transluminal coronary angioplasty, excimer laser coronary angioplasty (ELCA), rotational atherectomy, and additional stent implantation. Baseline clinical and angiographic characteristics were similar between the gamma radiation and placebo groups. One- and 6-month clinical and angiographic outcomes were compared. The use of stenting compared with other devices was associated with increased late loss. Device selection used as adjunctive therapy did not influence the 30-day outcome. Patients treated with gamma radiation and placebo therapy had similar rates of composite major adverse coronary events (MACE) (death, Q-wave myocardial infarction, target vessel revascularization) (3% vs 2%, p = NS). At 6 months, MACE rates in irradiated patients were similar among POBA (29%), ELCA (28%), rotational atherectomy (18%), and additional stent implantation (30%, p = NS), and were significantly lower compared with placebo for the entire cohort and for each device subgroup. The overall recurrence rate of ISR was lower in patients treated with gamma radiation using iridium-192 compared with placebo. Device selection did not influence late clinical outcomes in irradiated and nonirradiated groups.

PhotoPoint photodynamic therapy with local drug delivery eliminates vessel wall cells in arteriovenous graft models.

PURPOSE: To demonstrate the feasibility of PhotoPoint photodynamic therapy (PDT) with local drug delivery, optimize dosimetry in a rabbit jugular vein model, and investigate its ability to deplete potential neointimal precursor cells in the vessel wall in a canine arteriovenous graft (AVG) model. METHODS AND MATERIALS: Photosensitizer MV2101 was administered locally in rabbit veins, incubated for 0-40 min and activated with external laser light. In canine veins, MV2101 was incubated for 30 min and activated by light. Tissues were excised at acute and chronic timepoints. RESULTS: PhotoPoint PDT reduced cell populations in both models with maximum depletions occurring at 20 min (> or = 100 J/cm2) in rabbit veins (> 90% depletion) and 30 min (200 J/cm2) in canine veins (> 85% depletion). Chronic veins revealed no evidence of PhotoPoint PDT-related abnormalities. CONCLUSIONS: PhotoPoint PDT with local MV2101 dramatically depleted potential neointimal precursor cells in the vessel wall. This suggests local drug delivery is feasible and that PhotoPoint PDT may be an efficacious treatment that could prolong AVG patency in the clinic.

Failure of a novel balloon-expandable gamma-emitting ((103)Pd) stent to prevent edge effects.

BACKGROUND: Balloon-expandable beta-particle-emitting ((32)P) stents inhibit within-stent neointimal hyperplasia but induce lumen narrowing beyond the stent margins, ie, the so-called "edge effects." METHODS AND RESULTS: We prospectively investigated the performance of novel stents impregnated with the gamma-emitting isotope (103)Pd, designed to reduce edge effects, in 24 rabbits. The stents had a length of 18 mm and were mounted on 20-mm-long delivery balloons for deployment. Angiograms were obtained immediately and 1 month after direct implantation of control and 1-, 2-, and 4-mCi (103)Pd stents into the iliac arteries without predilatation or postdilatation. Late lumen loss was measured with quantitative angiography. Neointimal hyperplasia and vascular remodeling were evaluated by histomorphometry. Late lumen loss was inhibited within (103)Pd stents (control 0.18 mm, 1 mCi 0.08 mm, 2 mCi 0.05 mm, and 4 mCi -0.03 mm, P<0.05 all activities versus control). Conversely, late lumen loss occurred at the edges of (103)Pd stents, correlating with areas of high balloon/artery ratios and vessel overstretch injury. Edge effects were primarily due to neointimal hyperplasia but were also caused by negative vessel remodeling at high stent activities. CONCLUSIONS: Edge effects after implantation of radioisotope stents can occur independently of the isotope chosen for stent impregnation.

"Edge Effect" of (32)p radioactive stents is caused by the combination of chronic stent injury and radioactive dose falloff.

BACKGROUND: Radioactive stents have been reported to reduce in-stent neointimal thickening. An unexpected increase in neointimal response was observed, however, at the stent-to-artery transitions, the so-called "edge effect." To investigate the factors involved in this edge effect, we studied stents with 1 radioactive half and 1 regular nonradioactive half, thereby creating a midstent radioactive dose-falloff zone next to a nonradioactive stent-artery transition at one side and a radioactive stent-artery transition at the other side. METHODS AND RESULTS: Half-radioactive stents (n=20) and nonradioactive control stents (n=10) were implanted in the coronary arteries of Yucatan micropigs. Animals received aspirin and clopidogrel as antithrombotics. After 4 weeks, a significant midstent stenosis was observed by angiography in the half-radioactive stents. Two animals died suddenly because of coronary occlusion at this mid zone at 8 and 10 weeks. At 12-week follow-up angiography, intravascular ultrasound and histomorphometry showed a significant neointimal thickening at the midstent dose-falloff zone of the half-radioactive stents, but not at the stent-to-artery transitions at both extremities. Such a midstent response (mean angiographic late loss 1.0 mm) was not observed in the nonradioactive stents (mean loss 0.4 to 0.6 mm; P< 0.01). CONCLUSIONS: The edge effect of high-dose radioactive stents in porcine coronary arteries is associated with the combination of stent injury and radioactive dose falloff.