Daniel Todaro

Prospective Randomized Comparison of Sirolimus- or Everolimus-Eluting Stent to Treat Bifurcated Lesions by Provisional Approach

OBJECTIVES This study sought to compare the procedural performance and the acute angiographic result on side-branch ostium obtained using 2 different drug-eluting stents (DES) to treat patients with bifurcated coronary lesions. BACKGROUND Drug-eluting stents are routinely used in percutaneous coronary interventions (PCI) of bifurcated coronary lesions. Different DES types have major technical differences that may influence the procedural and clinical performance in bifurcation PCI. METHODS Consecutive patients with bifurcated lesions undergoing DES implantation using a systematic provisional-stenting strategy were randomized to sirolimus-eluting stent (SES) or everolimus-eluting stent (EES) before intervention. The procedural details for PCI were prospectively recorded to assess the occurrence of any trouble in the side-branch (SB) management (primary end point). Post-PCI angiographic result (primary end point: minimal lumen diameter at SB ostium) was evaluated offline by 3-dimensional reconstruction and quantitative coronary analysis. Clinical outcome was prospectively recorded up to 18 months to assess the occurrence of target bifurcation failure. RESULTS A total of 150 patients were enrolled in the study (29% diabetics, 17% unprotected left main). The stent was successfully implanted according to randomization in all cases. Procedural performance was not significantly different between the 2 kinds of DES. Three-dimensional reconstruction and quantitative coronary analysis showed similar post-PCI results in the main vessel and better results in the SB with EES than with SES (minimal lumen diameter at SB ostium: 1.94 ± 0.72 mm vs. 1.64 ± 0.62 mm; p = 0.013). At 18 months, target bifurcation failure occurred in 7 (9.0%) of SES-treated patients versus 8 (10.7%) of EES patients (p = 0.57). CONCLUSIONS In patients with bifurcated lesions treated by provisional stenting technique, EES compared with SES is associated with similar procedural performance and better 3-dimensional reconstruction and quantitative coronary analysis result in the SB. Both DES are associated with low rates of major adverse events and angiographic failure. (Sirolimus Versus Everolimus-Eluting Stent Randomized Assessment in Bifurcated Lesions and Clinical Significance of Residual Side-Branch Stenosis [SEA-SIDE]; NCT00697372).

MicroRNAs and ischemic heart disease: towards a better comprehension of pathogenesis, new diagnostic tools and new therapeutic targets.

MicroRNAs are key, recently discovered, regulators of gene expression. They are involved in many physiological cellular pathways so it is not surprising that an altered microRNA expression pattern can be involved in the pathogenesis of many disease states. The possibility to manipulate microRNAs to obtain a therapeutical effect is very attractive since they represent specific targets in a particular cellular pathway and because it is quite easy to synthesize short oligonucleotides with the ability to interfere with microRNA mechanism of action. The main problem for microRNA-based therapy is represented by delivery. In the last two years many studies have underlined the involvement of microRNAs in many aspects of ischemic heart disease, the leading cause of morbidity and mortality in the Western World. MiR-29 is involved in fibrotic reaction after myocardial infarction while miR-21 may exert a fundamental role in post-angioplasty restenosis. MiR-208 is involved in the shift toward a fetal gene expression pattern in contractile proteins in heart failure. MiR-1 influences susceptibility to cardiac arrhythmias after myocardial infarction. This review will focus on microRNAs involvement in multiple aspects of ischemic heart disease and on their promising novel therapeutic applications including some recent patents.

Kissing inflation is feasible with all second-generation drug-eluting balloons.

OBJECTIVE To assess the feasibility of kissing second-generation drug-eluting balloons (DEB), which have better mechanical properties than the first-generation DEB, in order to optimize provisional bare-metal stenting (BMS) when treating coronary bifurcation lesions in patients with contraindication to drug-eluting stents. METHODS Consecutive patients with anticipated low compliance to dual antiplatelet therapy who are undergoing provisional stenting with an open-cell design BMS and final kissing balloon with second-generation DEB were enrolled in this feasibility study. Angiographic success and procedural success (i.e., angiographic success in absence of in hospital major cardiovascular events) were registered. Clinical follow-up was also attempted in all patients. RESULTS A total of 14 patients (mean age 66±9 years, nine men) participated on the study. The DEB used were SeQuent Please (B. Braun Melsungen, Berlin, Germany) in six patients, In.Pact Falcon (Medtronic Invatec, Roncadelle, Italy) in four patients, New Dior (Eurocor, Bonn, Germany) in two patients and Pantera Lux (Biotronik, Berlin, Germany) in another two patients. All procedures, but one, were performed by transradial access through a 6-French high-flow guiding catheter. True bifurcation was present in 50% of the patients. Angiographic and procedural success was obtained in all patients. At a mean follow-up of 234±81 days, all contacted patients were asymptomatic and free from major adverse cardiac events (including cardiac death, nonfatal myocardial infarction and target bifurcation revascularization). CONCLUSION At the advent of dedicated bifurcation stents, kissing DEB appears safe and effective and can be used to implement innovative, simpler, safer and possibly more effective bifurcation techniques. These remarkable results have laid the ground for an ongoing prospective registry of the kissing DEB technique (KISSING DEBBIE study, ClinicalTrials.gov NCT01009996).

Glycoprotein Iib/iiia inhibitor to reduce postpercutaneous coronary intervention myonecrosis and improve coronary flow in diabetics: the ‘optimize-it’ pilot randomized study

Background Subgroup analyses of trials enrolling acute coronary syndrome patients suggest that inhibition of glycoprotein IIb/IIIa can improve the outcome of diabetic patients undergoing percutaneous coronary interventions (PCIs), possibly by improving microvascular perfusion. However, the efficacy of small-molecule IIb/IIIa receptor inhibitors to improve microvascular perfusion in stable diabetic patients undergoing elective PCI has not been specifically investigated. Methods We randomized consecutive stable diabetic patients, undergoing elective PCI, to tirofiban or placebo groups along with double antiplatelet therapy. High-dose bolus (25 μg/kg per 3 min) of tirofiban was administered immediately before PCI followed by 8 h continuous infusion (0.15 μg/kg per min). Postprocedural myonecrosis was assessed prospectively by measurement of cardiac troponin T (cTnT) at 6 and 24 h after PCI. The primary end-points were post-PCI coronary flow estimated by corrected thrombolysis in myocardial infarction frame count and post-PCI myocardial infarction. Platelet aggregation was measured by platelet function analyser-100 values. Results Forty-six patients entered the study (22 randomized to placebo and 24 randomized to tirofiban). The study drug was associated with a significant increase of platelet function analyser-100 values that peaked immediately after PCI and was maintained at 6 h (pre-PCI: 131 ± 65 s; post-PCI: 222 ± 49 s; after 6 h: 219 ± 55 s). Post-PCI corrected thrombolysis in myocardial infarction frame count was similar in tirofiban and in placebo groups (10.2 ± 3.6 vs. 12.0 ± 7.6, P = 0.30, respectively). The prevalence of raised cTnT levels was similar in the two groups (25 vs. 30%, P = 0.56, respectively). At multivariate analysis, direct stenting (associated with reduced myonecrosis) and postdilatation (associated with increased myonecrosis) predicted cTnT elevation. Conclusion A high-dose bolus of tirofiban in stable diabetic patients undergoing elective PCI, along with double antiplatelet therapy, was associated with a significant further inhibition of platelet aggregation which, however, did not translate in a lower incidence of post-PCI distal embolization.

Comparison of the transradial and transfemoral approaches for coronary angiographic evaluation in patients with internal mammary artery grafts.

Objective Transradial access for coronary angiography may offer some advantages in comparison with conventional transfemoral access in specific subgroups of patients. Therefore, the aim of this study was to compare the transradial and transfemoral approaches in patients with previous coronary artery bypass graft (CABG) surgery using the left internal mammary artery (IMA). Methods The time to left IMA cannulation, the time needed for left IMA evaluation, and total procedure time were compared in 60 patients previously submitted to CABG surgery using the left IMA. The homolateral radial access was attempted in 20 consecutive patients (TR group), whereas the transfemoral approach was undertaken in 40 patients (2: 1, TF group), matched for age, sex and number of grafts. Results In the TR group, the time to left IMA cannulation and the time needed for left IMA evaluation were 39% and 46%, respectively, lower than those in the TF group (P = 0.01 and P = 0.001, respectively), whereas total procedure time was similar. In the subgroup of patients with less than three saphenous vein grafts (n = 36), the time to left IMA cannulation, the time needed for left IMA evaluation as well as total procedure time were significantly reduced (P = 0.01, P = 0.001 and P = 0.004, respectively). The rate of ad-hoc coronary angioplasty procedures was unaffected by the access site (20% in the TR group and 27% in the TF group, P = 0.53). Conclusions The present study shows that the homolateral transradial approach facilitates left IMA evaluation in patients with previous CABG surgery undergoing coronary angiography, in particular in patients with a lower number of coronary artery bypass conduits, in the absence of an excess of periprocedural complications.

Prospective evaluation of myocardial ischemia related to post‐procedural side‐branch stenosis in bifurcated lesions treated by provisional approach with drug‐eluting stents

Objectives: To prospectively assess the impact of post‐procedural side‐branch (SB) stenosis on inducible myocardial ischemia in patients with bifurcated lesions undergoing percutaneous interventions. Background: Provisional‐stenting with drug‐eluting stents (DES) is the recommended strategy to treat percutaneously bifurcated lesions but is associated to variable degrees of residual SB stenosis. The role of SB residual stenosis on post‐procedural myocardial ischemia is uncertain. Methods: Patients with bifurcations treated by DES according to provisional‐stenting technique were enrolled in the study if they had no other untreated lesion. Patients were divided into two groups according to post‐procedural 3D‐quantitative coronary analysis (3DQCA): group OR (optimal result: stenosis < 50% of SB lumen area at 3DQCA) and group SR, suboptimal result: (stenosis ≥ 50% of SB lumen area at 3DQCA). Treadmill exercise stress test (EST) was performed within 1 week from PCI. The primary study endpoint was myocardial ischemia (≥1 mm ST‐segment depression at EST). Results: Sixty patients were enrolled: 49 (81.7%) comprised group OR and 11 (18.3%) group SR. Post‐PCI myocardial ischemia at EST was inducible in 17 (34.7%) patients of group OR versus 10 (90.9%) patients of group SR (P = 0.0007). During the follow‐up, patients of Group SR (vs. Group OR) had a significantly higher occurrence of inducible myocardial ischemia during late (>8 weeks) stress tests (P < 0.001). Conclusions: In patients with bifurcated lesions treated by a provisional‐stenting technique, residual SB stenosis ≥ 50% at 3DQCA is associated with post‐procedural inducible myocardial ischemia at EST.

Outcome of patients treated by a novel thin-strut cobalt-chromium stent in the drug-eluting stent era: Results of the SKICE (Skylor in real world practice) registry.

Objectives: To investigate the outcome of patients undergoing percutaneous coronary interventions (PCI) with implantation of a new thin‐strut cobalt‐chromium bare‐metal‐stent (BMS) in the drug‐eluting‐stent (DES) era. Background: Despite the contemporary penetration of DES in the clinical practice, a relevant percentage of patients are still treated by BMS. Data on clinical outcome of novel BMSs are lacking. Methods: This is a single‐centre‐registry enrolling patients treated by Skylor™ stent implantation. During the study, the criteria for BMS selection adopted at our institution (“internal” criteria) were as follows: (1) limited compliance to prolonged double antiplatelet therapy, (2) ST‐elevation myocardial infarction (STEMI) or saphenous vein grafts (SVG) interventions, and (3) in the absence of these conditions, noncomplex (no bifurcations, no chronic total occlusions) lesions considered at low restenosis risk on the basis of arbitrary angiographic criteria (short lesions, large vessels). Primary and secondary end‐points were respectively major adverse cardiovascular events (MACE) and target vessel failure (TVF) up to 9‐month. Results: A total of 150 patients were treated with Skylor™ stent on 169 lesions. At 9‐month follow‐up, MACE occurred in 12 patients (8.0%) and TVF in 21 lesions (12.4%). By multivariable analysis, the predictors of MACE were Euroscore≥9 and ejection fraction < 30% while the predictors of TVF were the absence of the angiographic criteria of low restenosis risk and ejection fraction < 30%. Conclusions: In the DES era, the use of a last‐generation BMS in patients with limited compliance to double antiplatelet therapy, STEMI or SVG interventions, and noncomplex angiographic lesions may be associated with acceptable clinical outcome.

Comparative assessment of mammalian target of rapamycin inhibitor-eluting stents in the treatment of coronary artery bifurcation lesions: The CASTOR-Bifurcation registry†

Drug‐eluting stents (DES) have revolutionized the treatment of coronary bifurcation lesions. Among different DES types, sirolimus‐eluting stents (SES) showed better outcomes than paclitaxel‐eluting stents. Because novel sirolimus analogues have been implemented in DES, a prospective observational comparison was undertaken to compare major mammalian target of rapamycin inhibitor‐eluting stents in the treatment of bifurcation lesions according to the provisional T‐stenting and small protrusion (TAP) technique. Overall, 187 patients (165 men, 65 ± 10 years) were enrolled in the study: 80 patients received a SES, whereas zotarolimus‐eluting stents (ZES) were implanted in 53 patients and everolimus‐eluting stents (EvES) in 62 patients. Primary end‐point of the study was the 12‐month incidence of target bifurcation failure (TBF) defined as occurrence of cardiovascular death, nonfatal myocardial infarction (MI), and target vessel revascularization (TVR) or angiographic documentation of >50% restenosis on the main vessel or TIMI flow <3 on the side branch. Groups were homogeneous according to main clinical and angiographic characteristics. Overall, 17 (9.1%) patients had TBF: 4 (2.1%) patients had nonfatal non‐ST‐segment elevation MI, 9 (4.8%) patients underwent TVR, and 6 (3.2%) patients had an angiographic restenosis. The rate of TBF was statistically different among the three groups (7.9% in SES group, 18% in ZES group, and 3.3% in EvES group, P = 0.024). Previous MI was associated with a worse outcome (P = 0.025), whereas final kissing balloon was associated with a better outcome (P = 0.045). In conclusion, in this prospective registry, significant differences between DES were found in the outcome of patients treated for coronary bifurcation lesions according to provisional TAP technique. Thus, prospective randomized trials in this field are needed.

Comparison of two- and three-dimensional quantitative coronary angiography to intravascular ultrasound in the assessment of intermediate left main stenosis.

Angiographic evaluation of intermediate left main coronary artery stenosis (LMS) is often limited. Three-dimensional (3D) quantitative coronary angiography has recently developed to overcome 2-dimensional (2D) quantitative coronary angiographic (QCA) limitations. In patients with angiographically intermediate LMS, we investigated whether 3D quantitative coronary angiography was superior to 2D quantitative coronary angiography in predicting the presence of a significant LMS, defined as a minimum luminal area <6 mm(2) at intravascular ultrasound (IVUS). 2D and 3D quantitative coronary angiography were compared in their measurements of minimum luminal area, percent area stenosis, minimum luminal diameter, and percent diameter stenosis and in their prediction of an IVUS minimum luminal area <6 mm(2). In total 58 target lesions were interrogated, 25 (43%) of which had an IVUS minimum luminal area <6 mm(2). Correlation between 3D-QCA minimum luminal area and IVUS minimum luminal area was stronger than the correlation between 2D-QCA minimum luminal area (or minimum luminal diameter) and IVUS minimum luminal area (R = 0.67, p = 0.0001, and R = 0.40, p = 0.001, respectively, p = 0.04 for comparison). To predict IVUS minimum luminal area <6 mm(2), the most accurate 2D-QCA measurement was minimum luminal diameter (area under curve 0.81, cutoff 2.2 mm, p = 0.0001), and the most accurate 3D-QCA measurement was minimum luminal area (area under curve 0.86, cutoff 5.6 mm(2), p = 0.0001). 2D-QCA percent diameter stenosis did not significantly predict IVUS minimum luminal area <6 mm(2) (area under curve 0.56, cutoff 38%, p = 0.45). In conclusion, the accuracy of quantitative coronary angiography in predicting LM IVUS minimum luminal area <6 mm(2) is limited. When IVUS is not available or contraindicated, 3D quantitative coronary angiography may assist in the evaluation of intermediate LMS. Among 2D-QCA parameters, minimum luminal diameter is more accurate than percent diameter stenosis in predicting significant LMS.

Complexity and simplicity in percutaneous bifurcation interventions.

We read with interest the paper by Catakoglu and Aytekin describing a novel stenting technique aiming at ensuring side branch (SB) access when treating bifurcation lesions. We praise the commitment of the authors to preserve SB access, however, a few points of their strategy deserve some comments. As a first step, the authors recommend to predilate both the main vessel (MV) and the SB. Predilation of a SB without severe atherosclerotic disease is generally not recommended because of the risk of dissection and the subsequent probability to recross, through a dissection plane, a strut which is too proximal with respect to the carina. Bench testing of provisional stenting has indeed shown that rewiring through the strut closest to the carina provides a far better scaffolding than proximal rewiring. Accordingly, SB predilation is also discouraged in order to take advantage of the carina shift ensuing MV stenting so that the wire could cross the stent exactly at the carina level. In the highway technique, the incomplete stent expansion in the proximal MV due to the simultaneous inflation of a SB balloon is of concern for distal strut rewiring. Owing to stent underexpansion in the proximal MV, the stent cell which is closest to the carina is likely not facing the SB ostium, thus possibly preventing optimal SB rewiring. Just the opposite, optimisation of proximal MV stent expansion with a slightly bigger balloon (the so called POT, which stands for proximal optimisation technique) has been proposed as a mean to favour SB rewiring through the carina cell. Prior to this stage, the highway technique requires both SB balloon and SB wire to be removed. However, jailed wire removal should be avoided until effective recrossing has been performed because it marks the SB, it keeps it open and modifies favourably the angle between the two bifurcation branches. On the whole, the highway technique is a rather complex approach to improve SB access following provisional MV stenting. In the same issue of EuroIntervention, the description by Burzotta et al of the jailed balloon technique offers a far simpler approach to SB preservation when performing provisional stenting. When choosing this strategy, a balloon is just left jailed in the SB during MV stent inflation in order to reduce carina shift in addition to a favourable modification of the bifurcation angle. The jailed balloon helps rewire the SB; in case of an unsuccessful attempt, the jailed balloon may be inflated to displace the carina toward the MV, thus facilitating SB rewiring. A main concern with this technique is related to the possible risk of balloon entrapment in the SB, which, however, never happened in the authors descriptive series. In this respect, we would like to report an unexpected drawback that we encountered during our learning curve with the technique (Figure 1). Despite high pressure deployment of the MV stent, removal of its delivery catheter pulled the jailed balloon out of the SB due to friction between the stent delivery system and the shaft of the jailed balloon in the guiding catheter. We guess this harmless event could be reassuring about jailed balloon entrapment.