scholarly journals Coronary Endothelium‐Dependent Vasomotor Function After Drug‐Eluting Stent and Bioresorbable Scaffold Implantation

Author(s):  
Josep Gomez‐Lara ◽  
Loreto Oyarzabal ◽  
Luis Ortega‐Paz ◽  
Salvatore Brugaletta ◽  
Rafael Romaguera ◽  
...  

Background Early generation drug‐eluting stents (DESs) showed a high grade of coronary endothelial dysfunction that was attributed to lack of stent reendothelialization. Endothelium‐dependent vasomotor response of current DESs and bioresorbable scaffolds (BRSs) remains unknown. This study sought to assess the device‐related endothelial function of current devices and to correlate neointima healing with endothelial function. Methods and Results A total of 206 patients from 4 randomized trials treated with the durable‐polymer everolimus‐eluting Xience (n=44), bioresorbable‐polymer sirolimus‐eluting Orsiro (n=35), polymer‐free biolimus‐eluting Biofreedom (n=24), bioactive endothelial‐progenitor cell‐capturing sirolimus‐eluting Combo DES (n=25), polymer‐based everolimus‐eluting Absorb (n=44), and Mg‐based sirolimus‐eluting Magmaris BRS (n=34) underwent endothelium‐dependent vasomotor tests and optical coherence tomography imaging, as per protocol, at follow‐up. Crude vasomotor responses of distal segments to low‐dose acetylcholine (10 −6  mol/L) were different between groups: bioresorbablepolymer DEShad the worst (−8.4%±12.6%) and durable‐polymer DES had the most physiologic (−0.4%±11.8%; P =0.014). High‐dose acetylcholine (10 −4  mol/L) showed similar responses between groups (ranging from −10.8%±11.6% to −18.1%±15.4%; P =0.229). Device healing was different between devices. Uncovered struts ranged from 6.3%±7.1% (bioresorbable‐polymer DES) to 2.5%±4.5% (bioactive DES; P =0.056). In multivariate models, endothelium‐dependent vasomotor response was associated with age, bioresorbable‐polymer DES, and angiographic lumen loss, but not with strut coverage nor plaque type. Endothelial dysfunction (defined as ≥4% vasoconstriction) was observed in 46.6% of patients with low‐dose and 68.9% with high‐dose acetylcholine, without differences between groups. Conclusions At follow‐up, endothelial dysfunction was frequently observed in distal segments treated with current stents without remarkable differences between devices. Although neointima healing was different between devices, poor healing was not associated with endothelial dysfunction.

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Tetsuzo Wakatsuki ◽  
Koji Yamaguchi ◽  
Toshiyuki Niki ◽  
Kenya Kusunose ◽  
Kunihiko Koshiba ◽  
...  

Endothelial function remains chronically abnormal after vascular injury associated with coronary intervention. The long-term effects of drug-eluting stent (DES) on endothelial function are not known. We evaluated the endothelial-dependent vasomotor function and local release of pentraxin3 (PTX3) as a local inflammatory marker in nonrestenotic coronary arteries more than six months following DES and bare metal stent (BMS) implantation. Fifty-two patients treated six months earlier with a coronary stenting for isolated proximal left anterior descending (LAD) stenosis, with no evidence of restenosis, were studied. Twenty patients had been stented with BMS, and 32 had been with DES. Changes in diameter at distal site of the stented LAD in response to intracoronary acetylcholine (Ach) infusions (1,3,10,30 μg/min) were assessed by quantitative angiography. At the completion of the protocol, a 2mg bolus of isosorbide dinitrate (ISDN) was injected into the LAD. We also measured serum PTX3 levels sampled in coronary sinus (CS) and sinus of Valsalva (V). Results: The two groups had similar risk factors for endothelial dysfunction. The mean percent change in the diameter of the stented LAD by Ach injection was significantly more in the DES group than in the BMS group (−38.9±6.1 vs. −19.2±6.7 %, p<0.01). There was no significant difference in maximal dilation achieved by ISDN infusion between the two groups (34.6±6.6 vs. 31.2±4.6 %, NS). The translesional PTX3 gradient (CS-PTX3 minus V-PTX3) was higher in the DES group than in the BMS group (+0.11±0.05 vs. −0.01±0.05 ng/ml, p<0.01). More severe endothelial dysfunction was observed long term after DES implantation as compared to BMS. These findings were associated with an increased local inflammatory response to DES stenting.


2020 ◽  
Vol 52 (12) ◽  
pp. 841-849
Author(s):  
Chunmei Xu ◽  
Ping Wang ◽  
Huikai Miao ◽  
Tianyue Xie ◽  
Xiaojun Zhou ◽  
...  

AbstractA potential reduction of goiter volume (GV) of recombinant human thyrotropin (rhTSH) on multinodular goiters (MNG) was previously reported but controversial. Hence we conducted a meta-analysis to estimate the effect of rhTSH-stimulated radioiodine therapy in patients with MNG. PubMed, Cochrane, CNKI, VIP, and Wanfang databases were searched. Mean difference (MD) and odds ratios with 95% confidence intervals (95% CI) were derived by using an inverse variance random-effects model and fixed-effects model, respectively. Six studies (n=237) were involved in the analysis. For 12 months follow up, high dose (>0.1 mg) of rhTSH significantly reduced GV (MD=17.61; 95% CI=12.17 to 23.04; p<0.00001) compared with placebo. No effective pooled results of low dose of rhTSH (<0.1 mg) were applicable for only one study included. For 6 months follow up, the source of heterogeneity was determined by subgroup and sensitivity analysis. High dose group showed vast improvement in GV reduction (MD=16.62; 95% CI=1.34 to 31.90; p=0.03). The reduction of low dose group compared with placebo was inferior to high dose group. No available data were obtained to assess the influence of rhTSH after 36 months follow up for the only included study. Hypothyroidism incidence was higher for rhTSH group. No publication bias was seen. High dose of rhTSH treatment-stimulated radioactive 131I therapy after 6 months and 12 months follow up had a better effect in reducing GV, but with higher incidence of hypothyroidism. Owing to the limited methodological quality, more clinical researches are warranted in the future.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
Y Yamakami ◽  
S Kimura ◽  
K Hara ◽  
M Ohmori ◽  
R Tateishi ◽  
...  

Abstract Background Bioabsorbable polymer drug eluting stents (BP-DESs) were designed to reduce a vascular inflammatory reaction compared to durable polymer drug eluting stents (DP-DESs). However, few studies have compared vascular responses to BP-DESs and DP-DESs. Methods We enrolled 88 consecutive patients with single culprit coronary artery lesions (31 lesions with acute coronary syndrome) undergoing a single stent-implantation. BP-DESs and DP-DESs were implanted in 50 (57%) and 38 patients (43%), respectively. All lesions underwent optical coherence tomography examination at chronic phase and intrastent OCT findings at the follow-up were evaluated in every 1-mm cross-sections (CSs). Results A total of 1887 CSs (BP-DES: 1096, DP-DES: 791) were analyzed. The median period of follow-up OCT was 293 (250–374) days. There were no differences in the patient, lesion, and initial clinical presentation of acute coronary syndrome (ACS). BP-DESs had significantly higher percent neointimal hyperplasia area, defined as neointimal hyperplasia area divided by stent area x 100 (18.4±9.0% vs. 16.1±9.9%, p&lt;0.001), fewer malapposed struts (1.7% vs. 3.9%, p=0.005), fewer uncovered struts (3.6% vs. 5.8%, p=0.02) but higher frequency of superficial low intensity neointima (LIN) (7.7% vs. 3.4%, p&lt;0.001). Multivariate logistic analysis showed that BP-DES (OR: 2.5, 95% CI: 1.49–4.08, p&lt;0.001) and the initial clinical presentation of ACS (OR: 2.31, 95% CI: 1.47–3.62, p&lt;0.001) are independent predictive factors for LIN. Conclusion BP-DESs showed homogenous neointimal growth and complete stent coverage quantitatively. Meanwhile, the significant relationships of BP-DES with LIN may suggest that the neointimal quality remains immature in BP-DESs in this period. Funding Acknowledgement Type of funding source: None


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Ping-Yen Liu ◽  
Ping-Yen Liu ◽  
Yen-Wen Liu ◽  
Li-Jen Lin ◽  
Jyh-Hong Chen ◽  
...  

Background: By inhibiting HMG-CoA reductase, statins not only inhibit cholesterol biosynthesis, but also decrease the formation of isoprenoids, which are important for mediating signaling through the Rho/Rho kinase (ROCK) pathway. In animal studies, inhibition of ROCK by statins improves endothelial function, decreases inflammation, and prevents atherosclerosis. These so-called cholesterol-independent effects of statins are dose-related and may contribute to some of their clinical benefits. We hypothesize that ezetimibe, which inhibits cholesterol absorption, does not exert these cholesterol-independent effects in humans. Methods and Results: We studied 60 dyslipidemia subjects (n=20 in each arm) in a prospective, randomized, observer-blinded study comparing treatment with simvastatin 40 mg/d or simvastatin/ezetimibe 10/10 mg/d to corresponding placebo tablets for 28 days. Prior statin usage was comparable between the groups and a washout period of 2 weeks was instituted before enrollment. Blood samples for fasting lipids, leukocyte ROCK activity and C-reactive protein (CRP) were collected at days 0 and 28. Baseline demographics, lipid levels, ROCK activity and CRP were not different between the 3 groups. Compared to placebo group, both treatment regimens decreased low-density lipoprotein cholesterol (LDL-C) by 38% and CRP by 32– 42% after 28 days (p<0.001 for both compared to placebo). Although LDL-C and CRP were reduced to comparable levels by either lipid-lowering regimen (p>0.05 between the groups), only simvastatin 40 mg reduced ROCK activity and improved forearm flow-mediated vasodilatation (FMD) (p<0.01 for both compared to baseline). The reduction of ROCK activity with simvastatin 40 mg remained significant even after controlling for changes in LDL-C (p=0.01) and correlated with improvement in FMD (R 2 =0.78, p<0.01). However, there was no correlation between changes in FMD with changes in LDL-C or CRP. Conclusions: These findings suggest that despite comparable decrease in LDL-C and CRP, high-dose statin monotherapy has greater effects on both ROCK activity and endothelial function than low-dose statin and ezetimibe. These findings provide additional evidence of potential statin benefits beyond cholesterol lowering.


2020 ◽  
pp. postgradmedj-2020-138243
Author(s):  
Ratna Andriyati ◽  
Doni Firman ◽  
Yovi Kurniawati ◽  
Amir Aziz Alkatiri ◽  
Raymond Pranata ◽  
...  

BackgroundStudies comparing the clinical outcomes of second-generation biodegradable polymer drug-eluting stents (BP-DES) and second-generation durable polymer drug-eluting stents (DP-DES) in patients with ST-segment elevation myocardial infarction (STEMI) with follow-up duration of more than 1 year are still limited.ObjectiveThis study aimed to compare the 2-year clinical outcome of BP-DES with second-generation DP-DES in patients undergoing primary percutaneous coronary intervention (PPCI).MethodsThis is a retrospective cohort study in patients with STEMI, the primary endpoint was major adverse cardiac events (MACE) defined as recurrent myocardial infarction, total repeat revascularisation and cardiac death. The secondary endpoint was stent thrombosis (ST) defined as definite, probable or possible.ResultsA total of 400 patients were analysed (197 BP-DES groups and 203 DP-DES groups). BP-DES were independently associated with lower incidence of MACE (adjusted HR 0.67, 95% CI 0.21 to 0.91, p=0.005) and ST (adjusted HR 0.62, 95% CI 0.19 to 0.73, p<0.016) within 2 years of follow-up. Subgroup analysis of MACE individual components showed that BP-DES were associated with lower cardiac deaths (HR 0.35; 95% CI 0.18 to 0.94; p<0.001) compared to DP-DES, but not recurrent myocardial infarction and total repeat revascularisation.ConclusionsBP-DES were associated with better clinical outcomes compared to second-generation DP-DES in patients with STEMI undergoing PPCI.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
Y Matsuhiro ◽  
M Nishino ◽  
H Nakamura ◽  
K Yasumoto ◽  
A Tanaka ◽  
...  

Abstract Background New generation drug eluting stents (DES) have improved target vessel failure as compared with early generation DES and bare metal stent. Contemporary several new generation DES are different each other regarding strut thickness and drug and polymer type. A little is known about which stent induces a more favorable vascular healing at follow up. Purpose In this study, we compared the vascular healing at 8-month follow up by optical coherence tomography (OCT) between 4 different kinds of new generation DES. Methods We enrolled 112 consecutive patients (121 lesions) who underwent PCI using 4 kinds of new generation DES including biodegradable-polymer everolimus-eluting stents (BP-EES), biodegradable-polymer sirolimus-eluting stents (BP-SES), durable-polymer everolimus-eluting stents (DP-EES) and durable-polymer zotarolimus-eluting stents (DP-ZES) and who underwent 8-month follow up angiogram and OCT between July 2016 and April 2018. We compared the OCT parameters including percentage of covered struts, uncovered struts, well-apposed and uncovered struts, malapposed strut and mean neointimal hyperplasia (NIH) thickness between them. Results BP-EES consisted of 29 lesions, BP-SES consisted of 25 lesions, DP-EES consisted of 38 lesions and DP-ZES consisted of 29 lesions. A total of 734 frames with 5163 struts in BP-EES, 481 frames with 4214 struts in BP-SES, 783 frames with 6119 struts in DP-EES and 583 frames with 4708 struts in DP-ZES were analyzed. As shown in a table, mean NIH thickness was significantly higher in BP-EES and BP-SES. Thus, we compared the OCT parameters between durable-polymer (DP) group including DP-ZES and DP-EES and biodegradable-polymer (BP) group including BP-EES and BP-SES. The percentage of uncovered struts was significantly lower and mean NIH thickness was significantly higher in BP group than DP group. Results of OCT parameters BP-EES (n=29) BP-SES (n=25) DP-EES (n=38) DP-ZES (n=29) P value BP group (n=54) DP group (n=67) P value Covered struts (%) 89.5±13.6 92.4±8.6 85.5±17.5 85.0±17.7 0.29 90.9±11.6 85.3±17.4 0.08 Uncovered struts (%) 8.8±10.8 7.1±8.7 14.5±17.5 15.0±17.7 0.14 8.0±9.9 14.7±17.4 0.03 Well-apposed and uncovered struts (%) 7.9±9.9 5.9±7.7 11.7±13.1 12.3±14.0 0.15 7.0±8.9 11.9±13.4 0.04 Malapposed struts (%) 0.8±1.6 1.3±2.2 2.7±5.8 2.7±4.7 0.33 1.0±1.9 2.7±5.3 0.07 Mean NIH thickness (μm) 102±57 121±48 78±28 88±33 <0.01 111±53 82±31 <0.01 Conclusion The present OCT study demonstrated that delayed neointimal healing characterized by the presence of uncovered struts and lower mean NIH thickness was less common in BP group than DP gruop. Biodegradable-polymer may be more favorable than durable-polymer from the point of view of vascular healing.


Author(s):  
Robert Ross ◽  
Brian Fuehrlein

This chapter provides a summary of a landmark study on substance use disorders. Which of the following is most effective for treatment of opioid dependence: levomethadyl acetate, buprenorphine, high-dose methadone, or low-dose methadone? Starting with that question, it describes the basics of the study, including funding, study location, who was studied, how many patients, study design, study intervention, follow-up, endpoints, results, and criticism and limitations. The chapter briefly reviews other relevant studies and information, discusses implications, and concludes with a relevant clinical case. The study demonstrates that buprenorphine, high-dose methadone, and levomethadyl acetate are equally effective in the treatment of opiate use disorder. All three treatments are significantly more effective than low-dose methadone.


Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Sarah E Hodges ◽  
Shervin Rahimpour ◽  
Luis Alejandro Antezana ◽  
Abena A Ansah-Yeboah ◽  
Rajeev Dharmapurikar ◽  
...  

Abstract INTRODUCTION Various new waveforms for spinal cord stimulation (SCS) have emerged in recent years, with limited data supporting their utility in a real-world clinical setting. We report real-world results of a protocolized workflow algorithm that allows for high dose (HD) and low dose (LD) neurostimulation in patients with chronic pain undergoing SCS trial or permanent procedures. METHODS Prospective data was collected using the ManageMySurgery (MMS) mobile device platform in patients undergoing Medtronic SCS trial and permanent implant procedures. E-consent was obtained through the HIPAA compliant, mobile software platform. All data was de-identified, aggregated and analyzed. RESULTS In total, 104 patients (37 trial SCS and 67 permanent SCS) participated. For SCS trial and permanent procedures, the protocolized workflow algorithm resulted in a 91% trial success rate with >50% pain relief. At long-term follow-up (3 to 12 mo), 86% of permanent SCS patients reported they were getting the same or more relief as during their SCS trial. For permanent SCS patients, 79% reported >50% improvement in overall pain and 58% had >50% improvement in low back pain. The protocolized workflow algorithm resulted in a 37% “remitter rate,” with these patients reporting themselves essentially pain free (VAS 0–3). Importantly, 52% of permanent implant patients stopped or reduced their ‘as needed’ pain medications by >50%. Additionally, 87% would recommend the same procedure to a friend or family member, 87% found device charging ‘easy’ or ‘very easy’ and 66% reported charging a few times a week or weekly. CONCLUSION A protocolized workflow algorithm that allows for HD and LD neurostimulation appears to have robust utility in providing meaningful pain relief and opiate reduction during both the SCS trial and permanent stages and at longer-term follow-up. Randomized controlled trials with extended follow-up are in progress.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 46-46 ◽  
Author(s):  
B. Bruno ◽  
M. Rotta ◽  
F. Patriarca ◽  
N. Mordini ◽  
B. Allione ◽  
...  

Abstract Allogeneic approaches employing low dose TBI nonmyeloablative conditionings reported a dramatic reduction of transplant-related mortality (TRM) compared to conventional high dose regimens in newly diagnosed multiple myeloma (MM) (Maloney et al, Blood, 2003). The role of allografting, however, compared to autologous HCT remains to be determined. From September 1999 to July 2004, 241 consecutive MM patients, up to the age of 65, were diagnosed at five academic Italian Institutions. Overall, 194/241 had natural siblings (Table 1): 158/194 (81%) were HLA typed, while 36/194 (19%) were not typed for the following reasons: patients not eligible for high dose chemotherapy (n. 14); siblings not eligible for peripheral hematopoietic cell (PHC) donation (n.11); patient refusal to high dose chemotherapy (n. 9), unknown (n.2). Seventy-six/158 (48%) with a matched donor were offered a tandem autologous- nonmyeloablative allogeneic HCT approach. Eventually, 56/76 (73%), the “auto-allo group”, were enrolled while 20 did not enter the tandem program as 5 siblings (5/76, 7%) were not eligible for PHC donation, 5 patients refused an allogeneic HCT, and 10 patients preferred allografting as a possible salvage treatment. Of 102 patients without matched donors or after refusal to allografting, 73, “double-auto group”, underwent a standard double autologous transplant while 29 received less intense treatments because of clinical conditions or patient preference. Table 1 Newly diagnosed pts 241 With sibs/without sibs 194 /47 (total 241) HLA typed /not HLA typed 158 /36 (total 194) Matched sibs /No matched sibs 76 /82 (total 158) Auto-Allo”/“Double Auto”/Other”“ 56 /73 /29 (total 158) After induction chemotherapy, patients of both groups underwent G-CSF mobilised autografting with high dose melphalan (200 mg/m2). In the “auto-allo” group, the autologous HCT was followed, 2-4 months later, by low dose (2.0 Gy) TBI, allogeneic PHC infusion, and post transplant mycophenolate mofetil and cyclosporin. In the “double-auto group”, patients received a second autologous HCT. Patients characteristics were as follows: age: 54 (range 34–65) vs 53 (range 33–64) (p=ns); stage III myeloma: 77% vs 64% (p=0.03); beta 2 microglobulin > 2,5 mg/dl: 75% vs 59% (p=0.005), for the “auto-allo group” and for “the double-auto group”, respectively. At the time of this analysis, 56/56 of the “auto-allo group” and 55/73 of “the double-auto group” had completed the transplant programs. After median follow up of 3 years (range 11–80 months), TRM was 11% vs 4% (p=0.09); complete remission rates, defined as the disappearance of the monoclonal paraprotein by immunofixation, were 46% vs 16% (p=0.0001); overall survivals were 84% versus 62% (p=0.003); progression free survivals were 75% vs 41% (p=0.00008); event free survivals were 61% (34/56)% vs 38% (30/73) (p=0.006) in the “auto-allo group” and in the “double-auto” group, respectively. Longer follow up is needed, however data suggest that the “auto- non myeloablative allo” approach is not inferior to “double autologous” HCT in newly diagnosed MM.


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