Classification and Current Treatment Options of In-Stent Restenosis

Coronary stent implantation is currently performed in > 80% of percutaneous coronary interventions. Its main late complication is the development of in-stent restenosis (ISR), occurring in 10-80% of lesions treated in daily practice. The classification by Mehran et al. is most commonly used. Current therapeutic options to treat ISR include repeat balloon angioplasty, repeat stenting, cutting balloon angioplasty, directional coronary atherectomy, rotational coronary atherectomy, brachytherapy, and drug-eluting stents (DES). DES have been effective in reducing binary restenosis in de novo lesions in randomized controlled trials. The novel use of DES to treat ISR has been shown to be safe and effective in multiple studies involving sirolimus- and paclitaxel-eluting stents. As DES implantation becomes more widespread, ISR in DES is emerging as a new problem. The use of debulking techniques to treat ISR in DES is to be cautioned against. In this new era, the optimal treatment of this new problem is currently unknown. We await further data to see whether repeat DES implantation may help solve this vexing clinical problem.     

The Acute Changes of Fractional Flow Reserve in DK (Double Kissing), Crush,and 1‐Stent Technique for True Bifurcation Lesions

Background: While many studies confirmed the importance of fractional flow reserve (FFR) in guiding complex percutaneous coronary interventions (PCI), data regarding the significance of FFR for bifurcation lesions are still lacking. Methods: Between October 2008 and October 2009, 51 patients with true bifurcation lesions were consecutively enrolled and randomized into double kissing (DK) crush (n = 25), and provisional 1‐stent (n = 26) groups. FFR measurements at baseline and hyperemia were measured at pre‐PCI, post‐PCI, and at 8‐month follow‐up. Results: Clinical follow‐ups were available in 100% of patients while only 33% of patients underwent angiographic follow‐up. Baseline clinical and angiographic characteristics were matched between the 2 groups. Pre‐PCI FFR of the main branch (MB) in the DK group was 0.76 ± 0.15, which was significantly lower than in the provisional 1‐stent group (0.83 ± 0.10, P = 0.029). This difference disappeared after the PCI procedure (0.92 ± 0.04 vs. 0.92 ± 0.05, P = 0.58). There were no significant differences in terms of baseline, angiographic, procedural indexes, and FFR of side branch (SB) between the 2 treatment arms. However, immediately after PCI, the patient with DK crush had higher FFR in the SB as compared to the provisional 1‐stent group (0.94 ± 0.03 vs. 0.90 ± 0.08, P = 0.028, respectively) and also they had lower diameter stenosis (8.59 ± 6.41% vs. 15.62 ± 11.69%, P = 0.015, respectively). Conclusion: In the acute phase, immediately after PCI for bifurcation lesion, DK crush stenting was associated with higher FFR and lower residual diameter stenosis in the SB, as compared with the provisional 1‐stent group. (J Interven Cardiol 2010;23:341–345)     

Randomized Comparison of FFR-Guided and Angiography-Guided Provisional Stenting of True Coronary Bifurcation Lesions: The DKCRUSH-VI Trial (Double Kissing Crush Versus Provisional Stenting Technique for Treatment of Coronary Bifurcation Lesions VI)

ObjectivesThis study sought to compare the outcomes of fractional flow reserve (FFR)–guided and angiography (Angio)–guided provisional side-branch (SB) stenting for true coronary bifurcation lesions.BackgroundAngio-guided provisional SB stenting after stenting of the main vessel provides favorable outcomes for the majority of coronary bifurcation lesions. Whether an FFR-guided provisional stenting approach is superior has not been studied.MethodsA total of 320 patients with single Medina 1,1,1 and 0,1,1 coronary bifurcation lesions undergoing stenting with a provisional SB approach were randomly assigned 1:1 to Angio-guided and FFR-guided groups. SB stenting was performed for Thrombolysis In Myocardial Infarction flow grade <3, ostial SB stenosis >70%, or greater than type A dissection after main vessel stenting in the Angio-guided group and for SB-FFR <0.80 in the FFR-guided group. The primary endpoint was the 1-year composite rate of major adverse cardiac events (cardiac death, myocardial infarction, and clinically driven target vessel revascularization).ResultsComparing the Angio-guided and FFR-guided groups, treatment of the SB (balloon or stenting) was performed in 63.1% and 56.3% of lesions respectively (p = 0.07); stenting of the SB was attempted in 38.1% and 25.9%, respectively (p = 0.01); and, when attempted, stenting was successful in 83.6% and 73.3% of SBs, respectively (p = 0.01). The 1-year composite major adverse cardiac event rate was 18.1% in both groups (hazard ratio: 0.91, 95% confidence interval: 0.48 to 1.88; p = 1.00). The 1-year target vessel revascularization and stent thrombosis rates were 6.9% and 5.6% (p = 0.82) and 1.3% and 0.6% (p = 0.56) in the Angio-guided and FFR-guided groups, respectively.ConclusionsIn this multicenter, randomized trial, angiographic and FFR guidance of provisional SB stenting of true coronary bifurcation lesions provided similar 1-year clinical outcomes. (Randomized Study on DK Crush Technique Versus Provisional Stenting Technique for Coronary Artery Bifurcation Lesions; ChiCTR-TRC-07000015)     

Angiographic and Clinical Outcomes after Implantation of Drug Eluting Stents in Bifurcation Lesions with Crush or Kissing Stent Technique

Background

Long‐term outcome after bifurcation stenting with drug‐eluting stents (DES) for obstructive coronary artery disease is poorly understood. In this study, we report 6–9‐month angiographic follow‐up and long‐term clinical outcomes after implantation of drug‐eluting stents by crush and kissing stent technique for coronary bifurcation lesions.

Methods

Consecutive patients undergoing bifurcation stenting with DES by crush or kissing stent technique were enrolled in a prospective registry. Angiographic follow‐up was obtained at 6–9 months and clinical follow‐up completed for a median of 38 months.

Results

A total of 86 patients participated in the study. Bifurcation stenting by crush technique was performed in 73 (85%) and by kissing stent in 13 (15%) patients. Stenting of left main bifurcation was applied in 24 (28%) patients. Angiographic follow‐up was completed in 75 (87%) patients and showed restenosis in the main for 8 (11%) and side branch for 20 (27%) patients. Clinical follow‐up was available for a median duration of 38 months. During follow‐up, 2 (2%) patients died, 4 (5%) experienced myocardial infarction (MI), and 11 (13%) underwent target vessel revascularization (TVR) with an overall major adverse cardiac event (MACE) rate of 16%. In left main cohort, angiographic restenosis occurred in 9 (37%) patients, and 3 (12%) patients required TVR. There were no deaths or stent thrombosis. A comparison of crush and kissing stent technique showed significantly higher angiographic restenosis with crush (26% vs 13% in kissing stent patients, P = 0.046) and 95% of restenosis in crush group involved ostium of the side branch. There was no difference in clinical outcomes between the crush and kissing stent groups. Final kissing balloon dilatation (FKB) was successful in 65 (89%) patients in the crush group and associated with a significant reduction in MACE (8% in FKB successful vs 37% in FKB unsuccessful, P = 0.04) during follow‐up.

Conclusion

Bifurcation stenting with crush or kissing stent technique is safe and associated with a low rate of TLR and MACE on long‐term follow‐up. Crush stenting is associated with a significantly higher rate of side branch restenosis compared to kissing stent technique. FKB is associated with significant reduction in MACE during follow‐up. (J Interven Cardiol 2013;26:145–152)

     

抗增殖药物涂层支架预防和治疗支架内再狭窄的临床研究进展

支架内再狭窄是介入治疗中的难题。新近多个有关雷帕霉素、紫杉醇涂层支架的临床试验显示药物涂层支架能有效预防支架内再狭窄。其对复杂病变的疗效有待于进一步研究。     

Comparison Among Drug-Eluting Balloon,Drug-Eluting Stent,and Plain Balloon Angioplasty for the Treatment of In-Stent Restenosis: A Network Meta-Analysis of 11 Randomized,Controlled Trials

ObjectivesA Bayesian network meta-analysis was performed comparing the efficacy and safety of drug-eluting balloons (DEB), drug-eluting stents (DES), or plain old balloon angioplasty (POBA) for treatment of in-stent restenosis (ISR).BackgroundOptimal treatment options for ISR have not been well established.MethodsRandomized, controlled trials comparing DEB, DES, and POBA for the treatment of ISR after percutaneous coronary intervention with bare metal stent or DES were included. The primary outcome was target lesion revascularization (TLR). The pairwise posterior median odds ratio (OR) with 95% credible interval (CrI) was the effect measure.ResultsThis analysis included 2,059 patients from 11 RCTs. The risk of TLR was markedly lower in patients treated with DEB (OR: 0.22, 95% CrI: 0.10 to 0.42) or DES (OR: 0.24, 95% CrI: 0.11 to 0.47) than in those treated with POBA in a random-effects model. In a comparison of DEB and DES, the risk of TLR (OR: 0.92, 95% CrI: 0.43 to 1.90) was similar. The risk of MI or all-cause mortality was lowest in the DEB group compared with the DES and POBA groups, which did not meet statistical significance. The risk of major adverse cardiac events, which was mainly driven by TLR, was also significantly lower in the DEB or and DES group (OR: 0.28, 95% CrI: 0.14 to 0.53) than in the POBA group, but it was similar between the DEB and DES groups (OR: 0.84, 95% CrI: 0.45 to 1.50). The probability of being ranked as the best treatment was 59.9% (DEB), 40.1% (DES), and 0.1% (POBA) in terms of TLR, whereas it was 63.0% (DEB), 35.3% (POBA), and 1.7% (DES) in terms of MI.ConclusionsLocal drug delivery by DEB or DES for ISR lesions was markedly better than POBA in preventing TLR, but not for MI or mortality. Among the 2 different strategies of drug delivery for ISR lesions, treatment with DEB showed a trend of less development of MI than did treatment with DES.     

Long-Term Outcomes of Left Main Bifurcation Double Stenting in Patients with STEMI and Cardiogenic Shock

The contribution of different left main (LM) bifurcation stenting techniques on long-term CV mortality has been poorly investigated. We evaluated the 3-year outcomes of revascularization of unprotected complex bifurcation LM in patients with cardiogenic shock (CS) with LM bifurcation/distal disease as culprit lesion. We analyzed 752 consecutive patients with STEMI admitted to our centre from 1 January 2014 to 1 March 2018, searching for patients with CS and complex distal/bifurcation LM disease as culprit lesion who received, at operators' discretion, LM double stenting by means of Culotte, T-stenting/TAP or Nano-crush technique. Fifty-seven patients (23 females, mean age 62.3 ± 10.5 years) with CS and STEMI with distal/bifurcation LM as culprit lesion were identified: 20 patients (35.0%) received Culotte, 16 patients (28.0%) received T-stenting/TAP and 20 (35.0%) received Nano-crush technique. At 3-year follow-up, clinical-driven target lesion revascularization, and mortality rate for all-causes were comparable among different stenting techniques. Conversely, considering 3-year CV mortality as outcome, a statistically significant difference was observed favoring Nano-crush when compared to patients treated with T stenting. Nano-crush obtained a larger improvement of ejection fraction on serial echocardiograms. CS with complex distal/bifurcation LM disease can be treated with acceptable rate of complication and short-term mortality using double stenting techniques. Techniques that minimize rewiring and kissing steps and shorten ischemic time should probably be preferred.     

Effectiveness and safety of sirolimus stent implantation for coronary in-stent restenosis: the TRUE (Tuscany Registry of Sirolimus for Unselected In-Stent Restenosis) Registry.

OBJECTIVES: This study sought to evaluate the effectiveness and safety of the sirolimus-eluting stent in the treatment of in-stent restenosis (ISR) in consecutive unselected patients undergoing coronary intervention in a real-world scenario. BACKGROUND: Restenosis after bare metal stenting is characterized by a high rate of re-restenosis once treated with repeated percutaneous coronary intervention. METHODS: The study was designed as a prospective two-center registry. We enrolled 244 patients with ISR in a native coronary artery or saphenous vein graft who had clinical indication for repeat intervention. RESULTS: Sirolimus stent implantation was successful in all lesions. At 9-month follow-up, death occurred in 4 (1.6%) patients, myocardial infarction in 4 (1.6%), and ischemia-driven target lesion revascularization (TLR) in 12 (4.9%), for a cumulative event-free survival of 227 (93%). Although 9-month follow-up angiography was planned in all patients, only 150 (62%) patients completed it, and restenosis was present in 13 (8.7%) patients. Diabetes and non-ST-segment elevation acute coronary syndrome at presentation were the only independent predictors of freedom from ischemia-driven TLR and major adverse cardiac events. CONCLUSIONS: Sirolimus stent implantation for the treatment of ISR is effective and safe. In diabetic patients and in those with acute coronary syndrome, the higher rate of recurrence requires further evaluation.     

Sympathetic Hyperactivity in Chronic Kidney Disease: Pathophysiology and (New) Treatment Options

Abundant evidence shows that chronic kidney disease (CKD) is a disease state characterized by increased sympathetic activation. Kidney injury (ischemia) plays a central role in this pathogenesis. Sympathetic excitation is associated with an increased risk of cardiovascular morbidity and mortality. Several pharmacologic strategies are developed to decrease sympathetic activity. However, these medications have limitations. Percutaneous catheter-based renal denervation has the potential to become a new treatment option for CKD. This current report focuses on the effects of sympathetic hyperactivity in CKD, and gives an overview in experimental as well as clinical evidence for a central role of the kidneys in the pathophysiology of sympathetic hyperactivity. Moreover, the effect of pharmacologic treatment and the potential beneficial effect of renal denervation will be discussed.