Drug-Coated Balloons for Treatment of Internal Carotid Artery Restenosis After Stenting: A Single-Center Mid-Term Outcome Study.

PURPOSE: Endovascular and surgical treatments of stenosis of the extracranial internal carotid artery (ICA) are common procedures, yet both introduce a risk of restenosis due to endothelial hyperplasia. Drug-coated balloons (DCBs) are designed to decrease neointimal hyperplasia, however rarely used in the neurovascular setting. This study retrospectively analyzes mid-term results of DCB-treated in-stent restenosis (ISR) of the ICA. MATERIALS AND METHODS: The medical history, comorbidities, and periprocedural data of patients receiving DCB treatment for > 50% ISR of the ICA after carotid artery stenting were analyzed. Follow-up after DCB treatment was performed with Doppler ultrasound. Suspicious cases were checked with CT- or MR-angiography and-if there was agreement between the modalities-validated with digital subtraction angiography. Potential risk factors for restenosis and differences in outcomes after PTA with three types of DCB balloons were evaluated. RESULTS: DCB treatment was performed in 109 cases, 0.9% of which involved in-hospital major stroke; no minor strokes occurred. A total of 17 patients (15.6%) had recurrent ISR after DCB treatment, after a mean time of 30.2 months (7-85 months). Tobacco use was significantly associated with a higher incidence of recurrent ISR. CONCLUSION: DCB angioplasty for ISR is an effective treatment that may delay and decrease restenosis. Treating comorbidities and adopting lifestyle changes may additionally help prevent ISR.

Systemic immune-inflammation index and in-stent restenosis in patients with acute coronary syndrome: a single-center retrospective study.

BACKGROUND: In-stent restenosis (ISR) has been shown to be correlated with inflammation. This study aimed to examine the relationship between systemic immune-inflammation index (SII, an innovative inflammatory biomarker) and ISR in acute coronary syndrome (ACS) patients after drug-eluting stent (DES) implantation. METHODS: Subjects who were diagnosed with ACS and underwent DES implantation were enrolled retrospectively. All individuals underwent follow-up coronary angiography at six to forty-eight months after percutaneous coronary intervention (PCI). SII was defined as [(platelet count × neutrophil count)/lymphocyte count], and Ln-transformed SII (LnSII) was carried out for our analysis. Multivariate logistic regression analysis was employed to assess the association between LnSII and DES-ISR. RESULTS: During a median follow-up period of 12 (11, 20) months, 523 ACS patients who underwent follow-up angiography were included. The incidence of DES-ISR was 11.28%, and patients in the higher LnSII tertile trended to show higher likelihoods of ISR (5.7% vs. 12.1% vs. 16.0%; P = 0.009). Moreover, each unit of increased LnSII was correlated with a 69% increased risk of DES-ISR (OR = 1.69, 95% CI 1.04-2.75). After final adjusting for confounders, a significant higher risk of DES-ISR (OR = 2.52, 95% CI 1.23-5.17) was found in participants in tertile 3 (≥ 6.7), compared with those in tertiles 1-2 (< 6.7). Subgroup analysis showed no significant dependence on age, gender, body mass index, current smoking, hypertension, and diabetes for this positive association (all P for interaction > 0.05). CONCLUSION: High levels of SII were independently associated with an increased risk of DES-ISR in ACS patients who underwent PCI. Further prospective cohort studies are still needed to validate our findings.

Systemic immune inflammation index and its implication on in-stent restenosis among patients with acute coronary syndrome.

OBJECTIVE: This study aims to assess the predictive value of the Systemic Immune Inflammation Index (SII) in determining in-stent restenosis (ISR) likelihood in patients with acute coronary syndrome (ACS) who have undergone percutaneous coronary intervention (PCI). METHODS: The study enrolled 903 ACS patients undergoing PCI, categorized into ISR (+) and ISR (-) groups based on control coronary angiography results. Demographic, clinical, laboratory, and angiographic-procedural characteristics were systematically compared. RESULTS: The ISR (+) group encompassed 264 individuals (29.2%), while the ISR (-) group comprised 639 individuals (70.8%). Patients had a mean age of 55.8 ±â€…10.2 years, with 69% being male. The ISR (+) group had higher diabetes and smoking prevalence and notably larger stent dimensions. Lab parameters showed significantly elevated creatinine, total cholesterol, red cell distribution width, white blood cell and neutrophil counts, SII index and C-reactive protein (CRP) in the ISR (+) group, while lymphocyte levels were lower. Binary logistic regression identified stent diameter (odds ratio [OR]: 0.598, 95% confidence interval [CI]: 0.383-0.935; P  = 0.024), stent length (OR: 1.166, 95% CI: 1.132-1.200; P  < 0.001), creatinine (OR: 0.366, 95% CI: 0.166-0.771; P  = 0.003), CRP (OR: 1.075, 95% CI: 1.042-1.110; P  = 0.031), and SII index (OR: 1.014, 95% CI: 1.001-1.023; P  < 0.001) as independent ISR predictors. CONCLUSION: The SII index exhibits potential as a predictive marker for ISR in ACS patients post-PCI, indicating systemic inflammation and heightened restenosis risk. Integrating the SII index into risk models could identify high-risk patients for targeted interventions.

Comprehensive clinical outcomes of drug-coated balloon treatment for coronary artery disease. Insights from a single-center experience.

BACKGROUND: Some clinical trials have verified the efficacy and safety of paclitaxel drug-coated balloon (DCB) for small vessel coronary artery disease. However, nonsmall vessel and calcified lesions received less attention. AIMS: This study aimed to investigate the efficacy of DCB treatment for various types of coronary artery lesions, including not only small vessel disease but also nonsmall vessel disease and calcified lesions. In this real-world clinical practice study, in-stent restenosis was excluded. METHODS: This study consecutively included 934 patients with 1751 nonstented lesions who received DCB at a cardiovascular center in Kyoto Katsura Hospital in Japan between 2009 and 2012 and 2014 to 2019. This study enrolled and retrospectively analyzed all of the patients. Eligible patients routinely underwent follow-up angiography at 6-8 months after percutaneous coronary intervention. The primary endpoint includes target lesion revascularization (TLR) during follow-up. Further, this study calculated the predictor of TLR using multivariate analysis. RESULTS: This study included the lesions involving 46.4% of type B2/C, 26.9% with severe calcification, and 6.0% with DCB restenosis. Mean DCB diameter and length were 2.75 ± 0.51 mm and 24.2 ± 9.6 mm, respectively. The median follow-up duration was 18 months. Follow-up angiography revealed a TLR rate of 9% and a restenosis rate of 9%. This study identified hemodialysis and current smoking as independent TLR predictors. CONCLUSION: In routine clinical practice, the effectiveness of DCB was observed consistently across various types of coronary artery disease.

A physics-informed deep learning framework for modeling of coronary in-stent restenosis.

Machine learning (ML) techniques have shown great potential in cardiovascular surgery, including real-time stenosis recognition, detection of stented coronary anomalies, and prediction of in-stent restenosis (ISR). However, estimating neointima evolution poses challenges for ML models due to limitations in manual measurements, variations in image quality, low data availability, and the difficulty of acquiring biological quantities. An effective in silico model is necessary to accurately capture the mechanisms leading to neointimal hyperplasia. Physics-informed neural networks (PINNs), a novel deep learning (DL) method, have emerged as a promising approach that integrates physical laws and measurements into modeling. PINNs have demonstrated success in solving partial differential equations (PDEs) and have been applied in various biological systems. This paper aims to develop a robust multiphysics surrogate model for ISR estimation using the physics-informed DL approach, incorporating biological constraints and drug elution effects. The model seeks to enhance prediction accuracy, provide insights into disease progression factors, and promote ISR diagnosis and treatment planning. A set of coupled advection-reaction-diffusion type PDEs is constructed to track the evolution of the influential factors associated with ISR, such as platelet-derived growth factor (PDGF), the transforming growth factor- ß (TGF- ß ), the extracellular matrix (ECM), the density of smooth muscle cells (SMC), and the drug concentration. The nature of PINNs allows for the integration of patient-specific data (procedure-related, clinical and genetic, etc.) into the model, improving prediction accuracy and assisting in the optimization of stent implantation parameters to mitigate risks. This research addresses the existing gap in predictive models for ISR using DL and holds the potential to enhance patient outcomes through predictive risk assessment.

A registry-based study of paclitaxel drug-coated balloon angioplasty for the treatment of in-stent restenosis of the femoral-popliteal artery.

OBJECTIVE: The aim of this study was to report the results of a prospective, single-arm, registry-based study assessing the safety and performance of a paclitaxel drug-coated balloon (DCB) for the treatment of superficial femoral artery (SFA) or popliteal artery in-stent restenosis (ISR) in a United States population. METHODS: We conducted a prospective, non-randomized, multi-center, single-arm, post-market registry of the IN.PACT Admiral DCB for the treatment of ISR lesions in the SFA or popliteal artery at 43 sites within the Society for Vascular Surgery (SVS) Vascular Quality Initiative (VQI) Registry from December 2016 to January 2020. Clinical outcomes were assessed at 12, 24, and 36 months. The primary endpoint was target lesion revascularization at 12 months. Secondary endpoints included technical success, target vessel revascularization, major limb amputation, and all-cause mortality. Results are presented as survival probabilities based on Kaplan-Meier survival estimates. RESULTS: Patients (N = 300) were 58% male, with a mean age of 68 ± 10 years. Diabetes was present in 56%, 80% presented with claudication, and 20% with rest pain. Lesions included ISR of the SFA in 68%, SFA-popliteal in 26%, and popliteal arteries in 7%. The mean lesion length was 17.8 ± 11.8 cm. Lesions were categorized as occlusions in 43% (mean occluded length, 16 ± 10 cm). TASC type was A (17%), B (29%), C (38%), and D (15%). Technical success was 99%. Re-stenting was performed in 5% and thrombolysis in 0.6% of patients. Kaplan-Meier estimates for freedom from target lesion revascularization were 90%, 72%, and 62% at 12, 24, and 36 months. Freedom from target vessel revascularization was 88%, 68%, and 59% and freedom from major target limb amputation was 99.6%, 98.9%, and 98.9%, respectively, at 12, 24, and 36 months. Survival was 95%, 89%, and 85% at 12, 24, and 36 months. CONCLUSIONS: This post-market registry-based study shows promising results in treating femoral-popliteal ISR with paclitaxel DCB in comparison to the results of plain balloon angioplasty reported in the literature. These results demonstrate the ability of the SVS VQI to conduct post-market evaluation of peripheral devices in partnership with industry and federal regulators.

Hypercholesterolemia exacerbates in-stent restenosis in rabbits: Studies of the mitigating effect of stent surface modification with a CD47-derived peptide.

BACKGROUND AND AIMS: Hypercholesterolemia (HC) has previously been shown to augment the restenotic response in animal models and humans. However, the mechanistic aspects of in-stent restenosis (ISR) on a hypercholesterolemic background, including potential augmentation of systemic and local inflammation precipitated by HC, are not completely understood. CD47 is a transmembrane protein known to abort crucial inflammatory pathways. Our studies have examined the interrelation between HC, inflammation, and ISR and investigated the therapeutic potential of stents coated with a CD47-derived peptide (pepCD47) in the hypercholesterolemic rabbit model. METHODS: PepCD47 was immobilized on metal foils and stents using polybisphosphonate coordination chemistry and pyridyldithio/thiol conjugation. Cytokine expression in buffy coat-derived cells cultured over bare metal (BM) and pepCD47-derivatized foils demonstrated an M2/M1 macrophage shift with pepCD47 coating. HC and normocholesterolemic (NC) rabbit cohorts underwent bilateral implantation of BM and pepCD47 stents (HC) or BM stents only (NC) in the iliac location. RESULTS: A 40 % inhibition of cell attachment to pepCD47-modified compared to BM surfaces was observed. HC increased neointimal growth at 4 weeks post BM stenting. These untoward outcomes were mitigated in hypercholesterolemic rabbits treated with pepCD47-derivatized stents. Compared to NC animals, inflammatory cytokine immunopositivity and macrophage infiltration of peri-strut areas increased in HC animals and were attenuated in HC rabbits treated with pepCD47 stents. CONCLUSIONS: Augmented inflammatory responses underlie severe ISR morphology in hypercholesterolemic rabbits. Blockage of initial platelet and leukocyte attachment to stent struts through CD47 functionalization of stents mitigates the pro-restenotic effects of hypercholesterolemia.

A case of repeated in-stent restenosis of coronary artery as a primary manifestation of seronegative antiphospholipid antibody syndrome.

BACKGROUND: Antiphospholipid antibody syndrome (APS) is a multisystemic autoimmune disorder which affects many organs or systems; however, coronary artery is relatively less frequently involved. CASE PRESENTATION: A 65-year-old female with effort chest pain was hospitalized for unstable angina in Janurary, 2015. Coronary angiography revealed sub-total occlusion of proximal left anterior descending (LAD) coronary artery, where a drug-eluting stent was successfully deployed. The patient experienced multiple in-stent stenosis at LAD coronary artery and coronary artery bypass graft (CABG) surgery was advised. Subsequently, severe stenosis of left circumflex (LCX) coronary artery emerged, and the patient suffered persistent in-stent restenosis. Eventually, the patient was diagnosed with seronegative antiphospholipid antibody syndrome and salvaged by immunosuppressants. CONCLUSIONS: Repeated in-stent restenosis could be a primary manifestation of seronegative antiphospholipid antibody syndrome, and suppression of autoimmune activity and inflammation other than purely coronary revascularization might be a better option.

Meta-analysis of risk factors for restenosis after stent implantation in patients with ischemic cerebrovascular disease.

OBJECTIVE: The aim of this study was to investigate the risk factors for restenosis after stent implantation in patients with ischemic cerebrovascular disease (ICVD), and to provide a reference for potential measures to prevent ICVD. MATERIALS AND METHODS: Relevant studies were identified by searching PubMed, ScienceDirect and Web of Science databases. Combined adjusted odds ratios and 95% confidence intervals were calculated. RESULTS: Seven case-control studies were identified in the end. Diabetes mellitus and residual stenosis were the two main risk factors for restenosis (OR = 0.59, 95% CI: 0.39-0.91, p = 0.01; OR = 36.73, 95% CI: 19.72-70.02, p < 0.001). Gender, smoking, hypertension, dyslipidemia, and stent type were not significantly associated with restenosis (OR = 0.85, 95% CI: 0.53-1.38, p = 0.52; OR = 1.30, 95% CI: 0.91-1.86, p = 0.15; OR = 0.86, 95% CI: 0.16-4.66, p = 0.86; OR = 1.30, 95% CI: 0.58-2.91, p = 0.53; OR = 1.34, 95% CI: 0.72-2.48, p = 0.35). CONCLUSIONS: The prevention of restenosis after stenting is particularly important for ICVD patients with diabetes or a high residual stenosis rate.

Risk factors for instent restenosis of sirolimus-coated stents in coronary intervention for patients with unstable angina.

To investigate the instent restenosis rate of sirolimus-coated stents in percutaneous coronary intervention (PCI) and risk factors for in-stent restenosis, patients with unstable angina (UA) caused by coronary artery stenosis were enrolled, and all clinical and imaging data were analyzed. Among 143 enrolled patients with UA aged 35-83 (mean 60.9 ± 10.0) years enrolled, there were 114 (79.7%) male and 29 (20.3%) female patients. Arterial stenosis was present in one coronary artery in 6 (4.2%) patients, in two coronary arteries in 20 (14.0%) patients, in three arteries in 116 (81.1%), and in four coronary arteries in 1 (0.7%) patient. Stenting was successfully performed in all (100%) patients, and 181 stents were deployed. The quantitative flow ratio (QFR) was 0.92 ± 0.03 (range 0.84-0.96) immediately after stenting, and the TIMI was grade 3 in all patients. The diameter of the stents deployed ranged 2.25-4 mm (mean 3.04 ± 0.44) with a length ranging 10 mm to 104 mm (mean 32.73 ± 15.5). Follow-up angiography was performed in all patients with a duration of 1-92 (mean 15.0 ± 18.8) months. Instent restenosis ≥ 50% occurred in 25 (17.5%) patients. In univariate logistic regression analysis, significant (P < 0.05) risk factors for instent restenosis ≥ 50% were QFR (OR 0.036, 95% CI 0.13-0.97), stent diameter (OR 0.43, 95% CI 0.18-0.92), hypertension (OR 3.16, 95% CI 1.02-9.82), smoking (OR 0.31, 95% CI 0.11-0.89), and neutrophil count (OR 2.22, 95% CI 1.10-5.44). In multivariate analysis, QFR (OR 0.02, 95% CI 0.002-0.19), stent diameter (OR 0.06, 95% CI 0.005-0.59), hypertension (OR 6.75, 95% CI 1.83-35.72) and neutrophil count (OR 276.07, 95% CI 12.32-10,959.95) were significant (P < 0.05) independent risk factors for instent restenosis ≥ 50%. In conclusion, certain instent restenosis rates occurs after the sirolimus-eluted coronary stent deployment for the treatment of coronary artery stenosis in patients with UA, and quantitative flow ratio after stenting, stent diameter, hypertension, and neutrophil count are significant risk factors for instent restenosis of the sirolimus-coated stents in coronary intervention.

Extreme coronary radiation doses from intravascular brachytherapy.

PURPOSE: To evaluate coronary artery integrity after very high radiation doses from intravascular brachytherapy (IVBT) in the setting of source asymmetry. METHODS: Ten patients treated for right coronary artery (RCA) in-stent restenosis (ISR) between 2017 and 2021 and for whom follow-up angiograms were available were identified from departmental records. Procedural angiograms, taken to document source position, were used to estimate vascular wall doses. The 2.5 mm proximal source marker was used to estimate the distance from source center to the media and adventitia. Distances were converted to dose (Gy) using the manufacturers' dose fall-off table, measured in water. Follow-up films were scrutinized for any sign of late vascular damage. RESULTS: The average minimal distance from catheter center to the adjacent media and the adventitia was 0.9 mm (±0.2) mm and 1.4 mm (±0.2), respectively. The average maximum media and adventitial doses adjacent to the source were 75 Gy (±26) and 39 Gy (±14), respectively. Follow-up angiograms were available from 0.6 years to 3.9 years following IVBT (median: 1.6 years). No IVBT-treated vascular segment showed signs of degeneration, dissection or aneurysm. CONCLUSION: IVBT vascular wall doses are frequently far higher than prescribed. The lack of complications in this unselected group of patients gives a modicum of reassurance that raising the prescription dose is unlikely to lead to a sudden appearance of complications.

Natural history of superior mesenteric artery in-stent restenosis.

OBJECTIVE: Superior mesenteric artery (SMA) stenting is the preferred approach for patients with symptomatic SMA-associated chronic mesenteric ischemia (CMI). The durability of this modality is impacted by in-stent restenosis (ISR). Duplex ultrasound (DUS) and computed tomographic angiography (CTA)-measured ISR may be weakly correlated and not uniformly associated with recurrence of presenting symptoms. This study aims to analyze the association between the degree of ISR for patients with CMI and to develop a predictive model for symptom recurrence. METHODS: Single center, retrospective study included all patients with CMI with SMA stents from the period of 2003 to 2020. Follow-up period analysis included patients' symptoms recurrence, DUS, CTA, and angiography. A receiver operating characteristic (ROC) analysis was used to evaluate whether peak systolic velocity (PSV) was predictive of symptom recurrence. A subgroup analysis of patients (asymptomatic and symptomatic) with SMA ISR was identified; restenosis defined by DUS with peak systolic velocity (PSV) ≥350. RESULTS: The study included 186 patients with the ROC analysis obtained from 503 postoperative visits. PSV was not a predictor of symptoms return with area under the curve (AUC) = 0.49 (95% confidence interval [CI], 0.40-0.57). Agreement analysis between imaging modalities showed higher agreement between CTA and angiogram (AUC, 0.769; 95% CI, 0.688-0.849) vs CTA and DUS (AUC, 0.650; 95% CI, 0.589-0.711). The subgroup analysis of patients with ISR included 99 patients (asymptomatic n = 67; symptomatic n = 32). There was no statistical difference between median time (months) to ISR between both groups: 4.5 (asymptomatic group) and 7.6 (symptomatic group). The use of preoperative antiplatelet (86% vs 65%; P = .015) and P2Y12 receptor blockers (36% vs 13%; P = .016) was more prevalent in the asymptomatic group. There was no difference between the type or number of stents placed, stent diameter, or concomitant celiac artery intervention between both groups. CONCLUSIONS: The natural history of SMA and multimodality defined ISR in CMI has not previously been described. Elevated PSV was a poor predictor of symptoms recurrence. Both asymptomatic and symptomatic patients with ISR did not differ in type of stent placed, time to ISR, or involvement of celiac artery. Antiplatelet use pre- and postoperatively appears protective against symptoms recurrence. Our findings underscore the need for long-term surveillance integrating clinical evaluation and multimodality imaging when indicated.

Fasting blood glucose predicts high risk of in-stent restenosis in patients undergoing primary percutaneous coronary intervention: a cohort study.

Objectives. Studies have shown that fasting blood glucose (FBG) is closely associated with poor prognosis in patients with coronary heart disease (CHD) after percutaneous coronary intervention (PCI), but its association with in-stent restenosis (ISR) is still unclear. Therefore, this study was to explore the association between FBG with ISR in patients with CHD after PCI. Design. In this cohort study, we included 531 patients with CHD who underwent PCI. Logistic regression, receiver operating characteristic (ROC), subgroup analysis and restricted cubic spline (RCS) were used to assess the association between FBG with ISR. Results. A total of 124 (23.4%) patients had ISR. Patients with higher levels of FBG had higher incidence of ISR compared to those with lower levels of FBG (p = 0.002). In multivariable logistic regression analyses, higher levels of FBG remained strongly associated with higher risk of ISR (as a categorical variable, OR: 1.89, 95% CI: 1.21-2.94, p = 0.005; as a continuous variable, OR: 1.12, 95% CI: 1.03-1.23, p = 0.011). ROC analysis also showed that FBG might be associated with the occurrence of ISR (AUC = 0.577, 95% CI: 0.52-0.64, p = 0.013). Subgroup analyses showed the association of FBG with ISR was also stable in several subgroups (< 60 years or ≥ 60 years, male, with or without smoking, without diabetes and without hypertension). And RCS analysis showed that FBG was linearly and positively associated with the risk of ISR. Conclusions. Higher levels of FBG were closely associated with higher risk of ISR in patients with CHD after PCI.

[Correlation between C-reactive protein to albumin ratio and restenosis after femoral popliteal stenting in patients with lower extremity arteriosclerotic obliterans].

Objective: To investigate the study of the correlation between C-reactive protein to albumin ratio (CAR) and restenosis after stenting in patients with lower extremity atherosclerotic occlusive disease(LEASO). Methods: The clinical data of 95 patients with LEASO admitted to the Department of Vascular Surgery of Nanjing Drum Tower Hospital from June 2020 to December 2022 were retrospectively analyzed. There were 67 males and 28 females,aged (73.1±9.4) years (range:51 to 92 years). The patients were classified into the restenosis group (n=61) and the patency group (n=34) according to the CT angiography results. Independent sample t test,Mann-Whitney U test and χ2 test were used to compare the data between two groups. Risk factors for restenosis after femoropopliteal artery stenting in patients with LEASO were analyzed using multivariate Cox regression. The relationship between preoperative CAR level and restenosis after stent placement was analyzed. Subject operating characteristic(ROC) curves of CAR were plotted to assess the predictive value of CAR for restenosis after stenting,and the results were expressed as area under the curve (AUC). Results: The aortoiliac calcification grade,number of stents,length of stents,C-reactive protein and CAR levels in restenosis group were higher than those in the patency group,and the serum albumin level was lower than that in the patency group(all P<0.05). And the results of multifactorial Cox regression analysis showed that higher pre-procedure CAR level and lower ABI value was an independent risk factor for in-stent restenosis. The AUC of the ROC curve for restenosis was 0.737(95%CI:0.617 to 0.856),the AUC of the ROC curve for 12-month restenosis was 0.709(95%CI:0.602 to 0.815), and the AUC of the ROC curve for 24-month restenosis was 0.702(95%CI:0.594 to 0.811). Conclusion: Higher pre-procedural CAR levels in patients with LEASO is risk factor for in-stent restenosis,and CAR has a predictive value for restenosis after lower extremity arterial stent dilatation and angioplasty.

Increased prescription dose for large vessel intravascular brachytherapy.

BACKGROUND: Most randomized studies testing the effectiveness of IVBT were limited to vessels less than 4 mm diameter. In fact, it is now common to treat vessels larger than 4 mm. Accordingly, the authors instituted a prescription dose increase to 34 Gy at 2 mm from source center for vessels greater than 4.0 mm. The increase in prescription dose to 34 Gy at 2 mm from center is substantial, being 50% higher than the conventional maximum of 23 Gy. AIM: To take a close look at group of patients treated to 34 Gy, and for whom follow-up angiograms are available. METHODS: Ten patients treated for ISR with a prescription dose of 34 Gy and for whom follow-up angiograms were available were studied. Beta-radiation brachytherapy was performed with a Novoste Beta-Cath System using a strontium-90 (beta) source (Best Vascular, Springfield, VA). Source lengths of 40 or 60 mm were used. A dose of 34 Gy was prescribed at 2 mm from the source center. RESULTS: Patients were re-catheterized from 2 to 21 months (median: 16 months) following IVBT, all for symptoms suggested of restenosis. All patients had some degree of ISR of the target vessel, but no IVBT-treated vascular segment showed angiographic signs of degeneration, dissection or aneurysm. CONCLUSION: The authors' clinical impression, along with detailed review of the 10 cases, suggest that using a 34 Gy prescription dose at 2 mm from source center does not result in increased toxicity.

Far-Infrared Irradiation Decreases Proliferation in Basal and PDGF-Stimulated VSMCs Through AMPK-Mediated Inhibition of mTOR/p70S6K Signaling Axis.

BACKGROUND: Far-infrared (FIR) irradiation has been reported to improve diverse cardiovascular diseases, including heart failure, hypertension, and atherosclerosis. The dysregulated proliferation of vascular smooth muscle cells (VSMCs) is well established to contribute to developing occlusive vascular diseases such as atherosclerosis and in-stent restenosis. However, the effects of FIR irradiation on VSMC proliferation and the underlying mechanism are unclear. This study investigated the molecular mechanism through which FIR irradiation inhibited VSMC proliferation. METHODS: We performed cell proliferation and cell death assay, adenosine 5'-triphosphate (ATP) assay, inhibitor studies, transfection of dominant negative (dn)-AMP-activated protein kinase (AMPK) α1 gene, and western blot analyses. We also conducted confocal microscopic image analyses and ex vivo studies using isolated rat aortas. RESULTS: FIR irradiation for 30 minutes decreased VSMC proliferation without altering the cell death. Furthermore, FIR irradiation accompanied decreases in phosphorylation of the mammalian target of rapamycin (mTOR) at Ser2448 (p-mTOR-Ser2448) and p70 S6 kinase (p70S6K) at Thr389 (p-p70S6K-Thr389). The phosphorylation of AMPK at Thr172 (p-AMPK-Thr172) was increased in FIR-irradiated VSMCs, which was accompanied by a decreased cellular ATP level. Similar to in vitro results, FIR irradiation increased p-AMPK-Thr172 and decreased p-mTOR-Ser2448 and p-p70S6K-Thr389 in isolated rat aortas. Pre-treatment with compound C, a specific AMPK inhibitor, or ectopic expression of dn-AMPKα1 gene, significantly reversed FIR irradiation-decreased VSMC proliferation, p-mTOR-Ser2448, and p-p70S6K-Thr389. On the other hand, hyperthermal stimulus (39°C) did not alter VSMC proliferation, cellular ATP level, and AMPK/mTOR/p70S6K phosphorylation. Finally, FIR irradiation attenuated platelet-derived growth factor (PDGF)-stimulated VSMC proliferation by increasing p-AMPK-Thr172, and decreasing p-mTOR-Ser2448 and p-p70S6K-Thr389 in PDGF-induced in vitro atherosclerosis model. CONCLUSION: These results show that FIR irradiation decreases the basal and PDGF-stimulated VSMC proliferation, at least in part, by the AMPK-mediated inhibition of mTOR/p70S6K signaling axis irrespective of its hyperthermal effect. These observations suggest that FIR therapy can be used to treat arterial narrowing diseases, including atherosclerosis and in-stent restenosis.

Quality of life for patients with in-stent restenosis after interventional therapy of peripheral artery disease.

OBJECTIVE: The aim of this study was to investigate the quality of life for patients with in-stent restenosis after interventional therapy of peripheral artery disease and the influencing factors. METHODS: A total of 72 in-stent restenosis patients after interventional therapy of peripheral artery disease were enrolled, whose general data were obtained. SF-12 scale was used to evaluate the quality of life. Tilburg Frailty Scale was used to assess senile debilitation. Pittsburgh Quality Index Scale was used to evaluate sleep quality. Activity of Daily Living Scale was used to evaluate the self-care ability. The general data and in-stent restenosis-related indicators were compared between patients with low and high quality of life, respectively. Multivariate regression analysis was made on the factors affecting quality of life. RESULTS: The average total quality of life score of 72 patients was 74.06±19.26 points. The gender, Fontaine stage and smoking, Activity of Daily Living Scale score, painless walking distance, senile debilitation score, sleep quality score, white blood cells, and C-reactive protein had significant differences between the two groups, respectively (p<0.05). Multivariate regression analysis showed that the female gender, low Fontaine stage (OR=0.186), low senile debilitation score (OR=0.492), and high sleep quality score (OR=0.633) were the protective factors for high quality of life (all p<0.05), and the low Activity of Daily Living score (OR=1.282) was the risk factor for high quality of life (p<0.05). CONCLUSION: Quality of life of in-stent restenosis patients after interventional therapy of peripheral artery disease is low. Gender, Fontaine stage, senile debilitation, sleep quality, and Activity of Daily Living score are the influencing factors of quality of life for in-stent restenosis patients.

Angioscopic and histopathological findings of in-stent restenosis in external iliac artery.

Little has been reported on the angioscopic and histopathological findings of in-stent restenosis (ISR) in the iliac artery. Here, we report a case of a male patient in his 70s who showed recurrent ISR in the right external iliac artery. We observed the ISR lesions with not only an intravascular ultrasound (IVUS) but also an angioscopy and a biopsy to clarify the mechanism of ISR. These imaging and histopathological findings showed neointimal hyperplasia, and we performed endovascular therapy with covered stent placement to prevent neointimal formation. Not only the IVUS but also the angioscopic and histopathological findings were helpful to clarify the mechanism of ISR and to determine the treatment plan.