Diagnosis and management challenges of in-stent restenosis in coronary arteries

Over the course of the 3 decades, percutaneous coronary intervention(PCI) with stent implantation transformed the practice of cardiology. PCI with stenting is currently the most widely performed procedure for the treatment of symptomatic coronary disease. In large trials, drugeluting stents(DES) have led to a significant reduction in in-stent restenosis(ISR) rates, one of the major limitations of bare-metal stents. Due to these favorable findings, DES was rapidly and widely adopted enabling more complex coronary interventions. Nevertheless, ISR remains a serious concern as late stent complications. ISR mainly results from aggressive neointimal proliferation and neoatherosclerosis. DES-ISR treatment continues to be challenging complications for interventional cardiologists.

Clinical Value of the Quantitative Flow Ratio to Predict Long-term Target Vessel Failure in Patients with In-stent Restenosis after Drug-coated Balloon Angioplasty

Objective The study sought to investigate the clinical predictive value of quantitative flow ratio(QFR)for the long-term target vessel failure(TVF)outcome in patients with in-stent restenosis(ISR)by using drug-coated balloon(DCB)treatment after a long-term follow-up.Methods This was a retrospective study.A total of 186 patients who underwent DCB angioplasty for ISR in two hospitals from March 2014 to September 2019 were enrolled.The QFR of the entire target vessel was measured offline.The primary endpoint was TVF,including target vessel-cardiac death(TV-CD),target vessel-myocardial infarction(TV-MI),and clinically driven-target vessel revascularization(CD-TVR).Results The follow-up time was 3.09±1.53 years,and 50 patients had TVF.The QFR immediately after percutaneous coronary intervention(PCI)was significantly lower in the TVF group than in the no-TVF group.Multivariable Cox regression analysis indicated that the QFR immediately after PCI was an excellent predictor for TVF after the long-term follow-up[hazard ratio(HR):5.15×10−5(6.13×10−8−0.043);P<0.01].Receiver-operating characteristic(ROC)curve analysis demonstrated that the optimal cut-off value of the QFR immediately after PCI for predicting the long-term TVF was 0.925(area under the curve:0.886,95%confidence interval:0.834–0.938;sensitivity:83.40%,specificity:88.00;P<0.01).In addition,QFR≤0.925 post-PCI was strongly correlated with the TVF,including TV-MI and CD-TVR(P<0.01).Conclusion The QFR immediately after PCI showed a high predictive value of TVF after a long-term follow-up in ISR patients who underwent DCB angioplasty.A lower QFR immediately after PCI was associated with a worse TVF outcome.

Aggressive restenosis after percutaneous intervention in two coronary loci in a patient with human immunodeficiency virus infection

A 54-year-old black African woman, 22 years human immunodeficiency virus(HIV)-positive, presented with an acute coronary syndrome. She was taking two nucleoside reverse transcriptase inhibitors and two protease inhibitors. Viral load and CD4 count were stable. Angiography revealed a right coronary artery lesion, which was treated with everolimus eluting stent. She also underwent balloon angioplasty to the first diagonal. She re-presented on three different occasions and technically successful coronary intervention was performed. The patient has reported satisfactory compliance with dual anti platelet therapy throughout. She was successfully treated with surgical revascularisation. The patient did not experience any clinical recurrence on follow up. This case demonstrates exceptionally aggressive multifocal and recurrent instent restenosis in a patient treated for HIV infection, raising the possibility of an association with HIV infection or potentially components of retro viral therapy.

Clinico-Angiographic Profile and Prevalence of Restenosis in Patients Undergoing Percutaneous Transluminal Coronary Angioplasty to Left Main Coronary Artery: An Observational Cohort Study

Background: Patients who underwent percutaneous coronary intervention in left main coronary artery (LMCA) requires special concern, being high risk and increasing patient population. The aim of this study was to assess the clinical profile, angiographic status, and prevalence of restenosis in patients who underwent percutaneous transluminal coronary angioplasty (PTCA) in LMCA. Materials and Methods: This observational cohort study included 17 patients who underwent PTCA in LMCA during one-year study period at tertiary care centers in Government Medical College, Kozhikode, India. Data including various risk factors, clinical and angiographic details, stent used, procedural complications and outcomes including rate of restenosis were analyzed. Results: A total of 17 patients (mean age 53.88 ± 9.80 years) with 76.47% of males were included in the study. Smoking and hypertension were the most common risk factors presented in 52.94% and 47.06% of patients respectively. Single vessel disease (SVD) of LMCA was the most common pattern observed in 47.10%;the rate of restenosis was observed in 11.76% patients. Revascularization was performed in one patient (5.88%) with coronary artery bypass graft and in one patient (5.88%) with PTCA using drug eluting stent (DES). The overall procedural success was 88.24% in this study. Survival rate was 100% at one-year follow-up period. Conclusion: Our study involved patients who underwent PTCA in LMCA, showed smoking as a most prevalent risk factor for coronary artery disease and SVD as a most common pattern, comparatively low rate of restenosis and 100% of survival rate at one-year follow-up period.

Incidence, Predictors, Treatment, and Long-Term Prognosis of Patients with Restenosis after Long Drug-Eluting Stent Implantation for Coronary Arteries

Background: Few data on the clinical course and management of patients experiencing restenosis after implantation of long drug-eluting stents treatment for coronary arteries was available. Objectives: The aim of this study was to evaluate the incidence, predictors, and long-term outcomes of patients with in-stent restenosis (ISR) after percutaneous coronary intervention (PCI) with long (33 mm & 38 mm) drug-eluting stents (DES) for long lesions in coronary arteries including left anterior descending artery (LAD), Lt circumflex artery (Lt Cx), right coronary artery (RCA), obtuse marginal artery (OM) & posterior descending artery (PDA). Methods: Between July 2009 and October 2010, 421 long DES had being implanted in 421 consecutive patients with significant coronary artery stenosis, with 371 patients (88%) undergoing routine follow up, clinical follow up done by exercise stress test at 6 & 12 months after stenting for 126 patients (34%), in 124 patients (33.5%) follow up was done by Computed Tomography angiography & 121 patients (32.5%) with clinically driven angiographic follow-up. A major adverse cardiac event was defined as the composite of death, myocardial infarction (MI), or target-lesion revascularization (TLR) within 15 months. Results: All patients who underwent clinical follow up were asymptomatic. The overall incidence of angiographic (CT or conventional) ISR with long (33 mm & 38 mm) DES was 4% (15 out of 371 stents) with 8 (53.3%) focal-type and 7 (46.7%) with diffuse-type ISR. Six patients (40%) under-went repeated PCI, seven (46.7%) underwent bypass surgery, and 2 (13.3%) were treated medically. During long-term follow-up (ranging from 12 - 26 months), there were no deaths, 3 (0.8%) MI, and 13 (3.5%) repeated target-lesion revascularization (PCI or CABG) cases. The incidence of major adverse cardiac event was 5.3% in the medical group, 10.1% in the repeated PCI group, and 21.4% in the bypass surgery group. Multivariate analysis showed that the occurrence of DES-ISR did not affect the risk of death or MI. Conclusions: The incidence of ISR was 4% after long DES stenting for coronary arteries. The long-term clinical prognosis of patients with long DES-ISR associated with coronary artery stenting might be benign, if the patient has optimal treatment.

Comparison of the safety and efficacy of two types of drug-eluting balloons （RESTORE DEB and SeQuent Please） in the treatment of coronary in-stent restenosis： study protocol for a randomized controlled trial （RESTORE ISR China）

1 Introduction In-stent restenosis （ISR）, characterized by neointimal proliferation and/or neoatherosclerosis in the vessel of the stent, can cause a reduction in lumen diameter after stent implantation, which can directly induce the recurrence of angina symptoms or an acute coronary syndrome in patients and is usually life-threatening.

Clinical Observation on Antiruisi Prescription (安替瑞丝方) in Preventing Restenosis after Coronary Artery Stenting

Antiruisi (AR)prescription (安替瑞丝方) is a compound in Chinese drug-therapy, which was used to treat 35 patients with coronary heart disease after stenting by the authors, and a satisfactory effect had been proved in preventing restenosis. It is reported as follows.

Multivariate Analysis of Clinical Factors in Restenosis after Coronary Stenting

Ojbective To find the independent predictors for restenosis after coronary stenting. Methods Quantitative angiography was performed on 60 cases (67 successfully dilated lesions) after angio-plasty over 6-months follow-up, and both univariate and multivariate logistic regression analysis were done to i-dentify the correlations of restenosis with clinical factors. Results The total restenosis rate was 31. 3% (21 of 67 lesions), and according to univariate analysis the patients who underwent coronary stenting≥ 3. 5mm had a lower rate of restenosis ( P < 0. 01). Collateral circulation to the obstruction site, high maximal inflation pressure, smoking and the less minimal lumen diameter after PTCA made the rate of restenosis higherower ( P < 0. 05) . Multivariate logistic regression analysis showed that coronary stenting ≥3. 5mm had a low rate of restenosis, but high maximal inflation pressure and smoking made the restenosis rate higher. Conclusion Coronary stent size, maximal inflation pressure and. smoking were independent predictors for restenosis.

Comparison of pre-dilation with a non-compliant balloon versus a dual wire scoring balloon for coronary stenting

Purpose: The aim of this study was to determine the influence of lesion preparation using the dual wire scoring balloon on stent expansion and long-term outcomes. Methods: Forty-six consecutive de novo lesions treated with a single >2.5 mm drug-eluting stent under intravascular ultrasound guidance, using two implantation strategies, were randomly assigned to: 1) pre-dilation with a non-compliant balloon (NC group;n = 23) or 2) pre-dilation with a dual wire scoring balloon (DS group;n = 23). Results: Although the balloon size and the maximal dilation pressure for pre-dilatation was larger (3.33 ± 0.28 vs 3.09 ± 0.33 mm, p = 0.01) and higher (11.6 ± 3.2 vs 8.6 ± 2.7 atm,

Increased serum TREM-1 level is associated with in-stent restenosis,and activation of TREM-1 promotes inflammation,proliferation and migration in vascular smooth muscle cells

Background and Objective In-stent restenosis(ISR)remains a major limitation of percutaneous coronary intervention despite improvements in stent design and pharmacological agents,whereas the mechanism of ISR has not been fully clarified.In the present study,we sought to investigate the potential association of serum soluble TREM-1(sTREM-1)levels with the incidence of ISR.The role of TREM-1 was evaluated in cultured vascular smooth muscle cells(VSMCs).

Clinical Observation on Shu Xin Yi Mai Capsules for Prevention of Recurrent Stricture after Coronary Artery Introducing Treatment

Shu Xin Yi Mai Capsules (舒心益脉胶囊) combined with western medicine was used in the routine treatment of 22 cases who successfully received coronary artery introducing therapy (Chinese-western medicine group),and the results was compared with the 26 cases treated routinely with simple western medicine in the control group (western medicine group).It was found that both the recurrence rate of angina pectoris and the incidence rate of recurrent stricture in the Chinese-western medicine group were significantly lower than that in the control group (both P<0.05).There was no significant difference between the two groups in expression of platelet activating molecules CD62P (a-granular membrane protein),CD63 (lysosome intact membrane protein) and CD41 (glucoprotein IIb) before the treatment,but with a significant difference after the treatment (P<0.05).

Comparison of Results of Coronary Angioplasty in Patients with Unstable vs. Stable Angina

Objectives To compare the short and mid - term outcomes in cases of percutaneous transluminal coronary angioplasty (PTCA) in patients with unstable v stable angina. Methods Patients selected for PTCA/stenting were divided in to two groups, one with stable angina pectoris (SA group, n = 92) and one with unstable angina pectoris (UA group, n = 112). The outcomes of coronary an giographies (CAG), initial (30-d) success of the procedure, and follow - up status in the two groups were compared. Results Baseline characteristics were similar, although the patients with unstable symptoms more females ( P< 0. 05), and had a higher average CCS class (P< 0. 05) and a higher incidence of postinfarction angina ( P< 0. 01). The frequency of ' complex stenosis in patients with unstable angina was higher than that of patients with stable angina, 33% v 20% ( P< 0. 01). A total of 309 vessels ac cepted the procedure; including 210 stents were sue cessfully delivered to 156 patients. 143 and 67 stents were implanted in the UA and SA group, respectively ( P< 0. 01 ) . No major complication occurred in the two groups, except 12 patients experienced reoccur ring chest pain initially, 9 in UA group v 3 in SA group ( P< 0. 05). The averaged six - month follow -up status was compared too. Only 3 cases developed myocardial infarction, including 2 patients with unsta ble angina. 12 and 16 reoccurring chest pains were found in the two groups, respectively ( 13% in SA group vs 14% in UA group). There were no signifi cant differences between groups in rates of clinical restenosis, follow - up angina class, or overall clinical success. Conclusions Patients with unstable angina receiving PTCA/stenting have similar complication, restenosis, and initial and midterm success rate as compared to patients with stable symptoms with strict cases select and careful preparation.

Potassium in Prevention of Restenosis after PTCA

Objectives To investigate safety and effectivity of potassium inprevention of restenosis after PTCA. Methods Eighty patients with PTCA were randomized into two groups: Control group ( Group Ⅱ n= 40) with conventional therapy; Treatment group (Group Ⅰ n = 40) with conventional therapy plus oral potassium (Slow - K 1.2 g, q8h, given 3 days before PTCA and continued to the end ofsub - study). Observation indeces of two groups were compared in follow - up. Results Seventy - seven patients were followed -up(39 in group Ⅰ, 38 in group Ⅱ) All blood indices (including fat, sugar, uric acid, cretonne, Na+, Cl-, Ca2+, Mg2+ ) except blood potassium in both groups were similar. Oral potassium could increase blood potassium level about 0. 3 mmol/L in group Ⅰ without causing any side effects. Suspicious angina pectoris and evidence of myocardial ischemia by ETT were developed in group Ⅱ had 14 patients (28. 9 % ) and Group I had 7 patients (17. 9 % ); 6 of 17 patients(35. 3 % ) in groupⅠ and 11 of 21 patients in group Ⅱ (52. 3 % ) appeared restenosis confirmed by coronary arteriography. 10. 2 % in group Ⅰ (4/39) and 23.7 % in group Ⅱ (9/38) needed revascular-izations(PTCA or CABG) . Conclusions Therapy with potassium after PTCA showed that recurrence of myocardial ischemia, restenosis rate by follow - up coronary arteriography and revascularization rate tended to be lower in group Ⅰ than in group Ⅱ.

Cutting balloon angioplasty for treatment of coronary in-stent restenosis: immediate results and 6-month outcomes

OBJECTIVE: To determine the mid-term effects of cutting balloon angioplasty (CBA) on in-stent restenosis. METHODS: A total of 69 patients with in-stent restenosis were divided into 2 groups randomly: cutting balloon angioplasty and plain old balloon angioplasty. The mechanisms of restenosis and dilation results were determined by quantitative coronary angiography and intravascular ultrasound. Follow-up was performed. RESULTS: The procedural success rate was 100% without death and acute closure. One patient experienced dissection at the distal end of the stent and needed another stent. The mean follow-up period was 6.7 +/- 2.3 months. The final re-restenosis rate was 15% and 18% at 3 months and 6 months respectively, markedly lower than after plain old balloon angioplasty (38% and 43%). Acute gain by intravascular ultrasound (IVUS) was 1.72 +/- 0.52 mm after cutting balloon angioplasty, higher than 1.15 +/- 0.54 mm after plain old balloon angioplasty. The lumen diameter late loss in the cutting balloon group was 0.26 +/- 0.05 mm and 0.38 +/- 0.06 mm at 3 months and 6 months respectively, significantly lower than for those in conventional balloon group (0.78 +/- 0.19 mm and 0.89 +/- 0.16 mm, respectively, P

经皮冠状动脉介入治疗术后再狭窄患者的凋亡抑制因子survivin水平及阿托伐他汀对其影响

目的探讨经皮冠状动脉介入治疗(PCI)术后再狭窄患者的血浆中凋亡抑制因子survivin水平及PCI术后短期应用阿托伐他汀对血浆survivin的影响。方法29例PCI术后6个月内复查冠状动脉造影的患者,按照冠状动脉造影结果分为再狭窄组(13例)、无再狭窄组(16例),并以同期冠状动脉造影完全正常者作为对照组(20例)。20例择期行PCI术的患者随机分为用药组和未用药组,用药组术后当天即予阿托伐他汀40mg/d,连用7d,两组其余治疗方案相同。采用酶联免疫吸附试验检测血浆survivin水平。结果再狭窄组的血浆survivin水平显著高于对照组和无再狭窄组(P值均<0.01),无再狭窄组的血浆survivin又显著高于对照组(P<0.01)。PCI术后患者血浆survivin水平于术后6h即急剧增高,未用药组在术后3d达最高峰,术后7d仍处于高水平;用药组于术后24h达最高峰;两组术后各时间点的血浆survivin水平均显著高于术前(P值均<0.01)。用药组术后3、7d的血浆survivin水平均显著低于未用药组(P值均<0.01)。结论PCI术后血浆survivin持续增高与PCI术后再狭窄有关,而阿托伐他汀可降低PCI术后血浆survivin的升高幅度。

A Multi-Center Randomized Double-Blind Placebo-Controlled Trial of Xiongshao Capsule(芎芍胶囊)in Preventing Restenosis after Percutaneous Coronary Intervention:A Subgroup Analysis of Senile Patients

Objective：To evaluate the safety and efficacy of Xiongshao Capsule（芎芍胶囊,XS）,consisting of Chuangxiongol and paeoniflorin,in preventing restenosis after percutaneous coronary intervention（PCI） in senile coronary heart disease（CHD） patients.Methods：A multi-center,randomized,double-blind,placebo-controlled trial was conducted.A total of 335 CHD patients were randomly assigned to treatment with oral administration of XS,or a placebo for 6 months after successful PCI.A clinical follow-up was performed at 1, 3 and 6 months after PCI and an angiographic follow-up was scheduled at 6 months.The primary endpoint was angiographic restenosis defined as a luminal stenosis≥50%in follow-up.The secondary endpoints were combined incidence of death,target lesion nonfatal myocardial infarction,repeat target-vessel angioplasty,and coronary artery bypass graft surgery（CABG）.The follow-up for the above clinical endpoint events was continued to 1 year after PCI.Results：The subgroup analysis of 152 senile patients（68 cases angiographic follow-up） showed that the restenosis rates tended to reduce in the XS group as compared with that in the placebo group （24.32%vs.38.71%,P0.05）,and the minimum lumen diameter（MLD） significantly increased in the follow-up （2.15±0.84 for XS vs.1.73±0.91 for placebo,P0.05）.The incidence of recurrent angina at 3 and 6 months after PCI was also significantly reduced in the XS group（4.11%and 12.33%） as compared with those in the placebo group（17.72%and 43.04%）,but there was no significant difference in the combined incidence of clinical outcomes（6.85%in the XS group vs.11.39%in the placebo group,P0.05）.No significant adverse reactions occurred within the 6-month follow-up period in the XS group.Conclusion：Administration of XS in addition to standardized Western medication for 6 months is demonstrated to be safe and effective in reducing post-PCI recurrent angina and inhibiting luminal restenosis after PCI in senile CHD patients.

Genetics of coronary artery disease and myocardial infarction

Atherosclerotic coronary artery disease(CAD) comprises a broad spectrum of clinical entities that include asymptomatic subclinical atherosclerosis and its clinical complications, such as angina pectoris, myocardial infarction(MI) and sudden cardiac death. CAD continues to be the leading cause of death in industrialized society. The long-recognized familial clustering of CAD suggests that genetics plays a central role in its development, with the heritability of CAD and MI estimated at approximately 50% to 60%. Understanding the genetic architecture of CAD and MI has proven to be difficult and costly due to the heterogeneity of clinical CAD and the underlying multi-decade complex pathophysiological processes that involve both genetic and environmental interactions. This review describes the clinical heterogeneity of CAD and MI to clarify the disease spectrum in genetic studies, provides a brief overview of the historical understanding and estimation of the heritability of CAD and MI, recounts major gene discoveries of potential causal mutations in familial CAD and MI, summarizes CAD and MIassociated genetic variants identified using candidate gene approaches and genome-wide association studies(GWAS), and summarizes the current status of the construction and validations of genetic risk scores for lifetime risk prediction and guidance for preventive strategies. Potential protective genetic factors against the development of CAD and MI are also discussed. Finally, GWAS have identified multiple genetic factors associated with an increased risk of in-stent restenosis following stent placement for obstructive CAD. This review will also address genetic factors associated with in-stent restenosis, which may ultimately guide clinical decision-making regarding revascularization strategies for patients with CAD and MI.

Assessment of Coronary Stents by 64-slice Computed Tomography: In-stent Lumen Visibility and Patency

Objective To assess lumen visibility of coronary stents by 64-slice computed tomography （CT） coronary angiography, and determine the value of 64-slice CT in non-invasive detecting of in-stent restenosis after coronary artery stent implantation. Methods Totally, 60 patients （54 males, aged 57.0±12.7 years） and /05 stents were investigated by 64-slice CT at a mean interval of 20.0±16.6 months after coronary stents implantation. Axial multi-planar reconstruction images of the stents and curved-planar reconstruction images through the median of the stents were reconstructed for evaluating stent image quality on a 5-point scale （1=excellent, 5=nonassessable）, and stent lumen diameter was detected. Conventional coronary angiography was performed in 18 patients, and 32 stents were evaluated. Results Image quality was good to excellent on average （score 1.71±0.76）. Stent image quality score was correlated to heart rate （r=0. 281, P〈0.01） and stent diameter （r=-0.480, P〈0.001）. All the stents were assessable in lumen visibility with an average visible lumen diameter percentage of 60.7%±13.6%. Visible lumen diameter percentage was correlated to heart rate （r=-0.193, P〈0.05）, stent diameter （r=0.403, P〈0.001）, and stent image quality score （r=-0.500, P〈0.001）. Visible lumen diameter percentage also varied depending on the stent type. In comparison with the conventional coronary angiography, 4 of 6 in-stent stenoses were correctly detected. The sensitivity and specificity for the detection of in-stent stenosis were 66.7% and 84.6%, respectively. Conclusions Using a 64-slice CT, the stent lumen is partly visible in most of the stents. And 64-slice CT may be useful in the assessment of stent patency.

Effect of Tongguan Capsules(通冠胶囊) on Restenosis after Coronary Stent Implantation:Study Protocol for A Randomized Controlled Trial

Background:Although percutaneous coronary intervention(PCI)had become widely employed therapeutic procedure for coronary artery disease,stent restenosis limited the benefits of this revascularization and the question how to prevent such events remained unresolved.While numerous empirical observations suggested Tongguan Capsules(通冠胶囊),a patented Chinese Medicine,could decrease frequency and duration of angina pectoris attacks,evidence supporting its efficacy on restenosis remained inadequate.Objective:This trial was designed to determine whether Tongguan Capsules would reduce restenosis rate in patients after successful stent implantation.Methods:Approximately 400 patients undergoing percutaneous coronary stent deployment were enrolled and randomized to control group or Tongguan Capsules(4.5 g/d)for 3 months.All patients received standard anti-platelet,anti-coagulation and lipid-decreasing treatments,concurrently.The primary clinical endpoint was the 12-month incidence of the major adverse cardiovascular events(defined as cardiac death,myocardial infarction,and recurrence of symptoms requiring additional revascularization).The angiographic end point was restenosis rate at 6 months.Conclusion:This study would provide important evidence for the use of Tongguan Capsules in patients after stent implantation in combination with routine therapies,which may significantly reduce incidence of the restenosis so as to potentially improve the clinical outcomes.(registration number:ChiCTR-TRC-ChiCTR-IIR-17011407)

Application of drug-coated balloon in coronary artery intervention： challenges and opportunities

In recent decades, the outcomes of coronary heart disease （CHD） have markedly improved, which can be partly attributed to the use of novel drugs （especially statins and antiplatelet drugs） and partly to the evolution ofpercutaneous coronary intervention （PCI）. From percutaneous transluminal coronary angioplasty to bare-metal stent and then to drug-eluting stent, every step of PCI is attractive to interventional cardiologist, great progress has been made for patients with CHD. In the past few years, some successor devices for treating CHD have cmerged. Undoubtedly, drug-coated balloon （DCB）, which was recommended by 2014 ESC Guidelines on myocardial revascularization, is a ＂shining star＂ among them. DCB involves a semi-compliant angioplasty balloon coated with an anti-proliferative agent that can exert antirestenotic efficacy by permeating into the vessel wall during balloon contact. This review discusses the conception and merits, preclinical data, emerging clinical indications, and results from clinical trials of this novel interventional technology. Although DCB has shown authentic efficacy in the treatment ofin-stent restenosis, its use in de novo coronary lesions is still in dispute. Hence, concerns and the future direction of DCB are also covered in this paper.