Salvatore D. Tomasello

In-hospital outcomes of percutaneous coronary intervention in patients with chronic total occlusion: insights from the ERCTO (European Registry of Chronic Total Occlusion) registry.

AIMSnIn comparison with non-occlusive lesions, percutaneous coronary intervention (PCI) of chronic total occlusions (CTO) represents a greater challenge for the interventionalist, due to lower procedural success rates, relatively higher incidence of procedural complications and the increased rate of restenosis. The European Registry of Chronic Total Occlusion (ERCTO) was created with the goal of evaluating the real impact of CTO PCI in the European context, trying to analyse the rates of procedural success, technical information from the CTO procedures and patient outcome.nnnMETHODS AND RESULTSnData collection was carried out in 16 centres across Europe, starting from the beginning of January 2008. In two years of activity, a total of 1,914 patients with 1,983 CTO lesions were consecutively enrolled in the registry. Overall procedural success was achieved in 1,607 lesions (82.9%); anterograde procedures obtained higher procedural success of retrograde ones (83.2% versus 64.5%, p<0.001). Coronary perforation occurred more frequently in patients who underwent retrograde approach (4.7% versus 2.1%, p=0.04). Although no differences were observed in terms of 30-day major adverse cardiac events between anterograde and retrograde treated patients, a trend toward higher periprocedural non-Q-wave myocardial infarction was found in patients in which the retrograde approach was attempted (2.1% versus 1% p=0.08). Moreover, retrograde approach was related with longer procedural and fluoroscopy times (156.9±62.5 min vs. 98.2±52.8 min and 73.3±59.9 min vs. 38.2±43.9 min respectively, p<0.001) and higher contrast load administration (402±161 cc vs. 302±184 cc, p<0.001).nnnCONCLUSIONSnThe first report of the ERCTO registry by the EuroCTO club shows a high procedural success rate obtained by expert European operators in a real-world consecutive series of patients, comparable with those reported by Japanese registries. The rate of observed procedural adverse events was low and similar to the non-CTO PCI series. In this registry, retrograde procedures were associated with extended fluoroscopy exposure and procedural time, increased contrast load administration as well as a higher incidence of coronary perforations. Such outcomes should become the standard of care that all centres undertaking CTO PCI should aspire to.

Recanalisation of chronic total coronary occlusions: 2012 consensus document from the EuroCTO club.

Georgios Sianos1*, MD, PhD, FESC; Gerald S. Werner2, MD, PhD, FESC, FACC, FSCI; Alfredo R. Galassi3, MD, FESC, FACC, FSCAI; Michail I. Papafaklis4, MD, PhD; Javier Escaned5, MD, PhD, FESC; David Hildick-Smith6, MD, FESC; Evald Hoj Christiansen7, MD, PhD; Anthony Gershlick8, MD, FRCP, FESC; Mauro Carlino9, MD, FESC; Angelos Karlas1, MD; Nikolaos V. Konstantinidis1, MD; Salvatore D. Tomasello3, MD; Carlo Di Mario10, MD, PhD, FRCP, FESC; Nicolaus Reifart11, MD, PhD, FESC for the EuroCTO Club

Pharmacodynamic Effects of Different Aspirin Dosing Regimens in Type 2 Diabetes Mellitus Patients With Coronary Artery Disease

Background— Patients with type 2 diabetes mellitus (T2DM) have reduced aspirin-induced pharmacodynamic effects. This may be attributed to increased platelet turnover rates resulting in an increased proportion of non–aspirin-inhibited platelets during the daily dosing interval. The hypothesis of this study was that an increase in the frequency of drug administration [twice daily (bid) versus once daily (od)] may provide more effective platelet inhibition in T2DM patients. Methods and Results— T2DM patients with stable coronary artery disease were prospectively recruited. Patients modified their aspirin regimen on a weekly basis according to the following scheme: 81 mg/od, 81 mg/bid, 162 mg/od, 162 mg/bid, and 325 mg/od. Pharmacodynamic assessments included light-transmittance aggregometry after arachidonic acid, collagen and adenosine diphosphate stimuli; VerifyNow-Aspirin assay; and serum thromboxane B2 (TXB2) levels. Twenty patients were analyzed. All patients were sensitive and compliant to aspirin irrespective of dose, as assessed by arachidonic acid–induced aggregation. When aspirin was administered once daily, there was no significant effect on platelet reactivity by increasing the once-daily dosing using aspirin-sensitive assays (collagen-induced aggregation and VerifyNow-Aspirin). An increase in aspirin dose by means of a second daily administration was associated with a significant reduction in platelet reactivity assessed by collagen-induced aggregation and VerifyNow-Aspirin between 81 mg/od and 81 mg/bid (P<0.05 for both assays) and between 81 mg/od and 162 mg/bid (P<0.05 for both assays). There was no impact of aspirin dosing regimens on adenosine diphosphate–induced aggregation. A dose-dependent effect of aspirin was observed on serum TXB2 levels (P=0.003). Conclusions— Aspirin dosing regimens are associated with different pharmacodynamic effects in platelets from T2DM patients and stable coronary artery disease, with a twice-daily, low-dose aspirin administration resulting in greater platelet inhibition than once-daily administration as assessed by aspirin-sensitive assays and a dose-dependent effect on serum TXB2 levels. The clinical implications of a modified aspirin regimen tailored to T2DM patients warrant further investigation. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01201785.

Retrograde Recanalization of Chronic Total Occlusions in Europe: Procedural, In-Hospital, and Long-Term Outcomes From the Multicenter ERCTO Registry

BACKGROUNDnA retrograde approach improves the success rate of percutaneous coronary interventions (PCIs) for chronic total occlusions (CTOs).nnnOBJECTIVESnThe authors describe the European experience with and outcomes of retrograde PCI revascularization for coronary CTOs.nnnMETHODSnFollow-up data were collected from 1,395 patients with 1,582 CTO lesions enrolled between January 2008 and December 2012 for retrograde CTO PCI at 44 European centers. Major adverse cardiac and cerebrovascular events were defined as the composite of cardiac death, myocardial infarction, stroke, and further revascularization.nnnRESULTSnThe mean patient age was 62.0 ± 10.4 years; 88.5% were men. Procedural and clinical success rates were 75.3% and 71.2%, respectively. The mean clinical follow-up duration was 24.7 ± 15.0 months. Compared with patients with failed retrograde PCI, successfully revascularized patients showed lower rates of cardiac death (0.6% vs. 4.3%, respectively; pxa0< 0.001), myocardial infarction (2.3% vs. 5.4%, respectively; pxa0= 0.001), further revascularization (8.6% vs. 23.6%, respectively; pxa0< 0.001), and major adverse cardiac and cerebrovascular events (8.7% vs. 23.9%, respectively; pxa0< 0.001). Female sex (hazard ratio [HR]: 2.06; 95% confidence interval [CI]: 1.33 to 3.18; pxa0= 0.001), prior PCIxa0(HR: 1.73; 95% CI: 1.16 to 2.60; pxa0= 0.011), low left ventricular ejection fraction (HR: 2.43; 95% CI: 1.22 to 4.83; pxa0=xa00.011), J-CTO (Multicenter CTO Registry in Japan) scorexa0≥3 (HR: 2.08; 95% CI: 1.32 to 3.27; pxa0= 0.002), and procedural failure (HR: 2.48; 95% CI: 1.72 to 3.57; pxa0< 0.001) were independent predictors of major adverse cardiac andxa0cerebrovascular events at long-term follow-up.nnnCONCLUSIONSnThe number of retrograde procedures in Europe has increased, with high percents of success, low rates of major complications, and good long-term outcomes.

Long‐term outcomes of bifurcation lesions after implantation of drug‐eluting stents with the “mini‐crush technique”

Objectives: To evaluate clinical and angiographic long‐term outcome of “the mini‐crush” technique for treating bifurcation lesions. Background: Despite proven efficacy of drug‐eluting stent (DES) within most lesions subsets, bifurcation lesions continue to exhibit high restenosis rate using current DES stenting technique. Methods: We report a new stenting technique which was employed in 45 consecutive patients (52 lesions) between April 2004 and July 2005 to treat true bifurcation lesions using DES in both branches. Results: Using this technique procedural success was obtained in 100% of cases, without complications and with excellent angiographic result in 96.1% and 98.1% of main vessel and side branch. Preprocedure reference vessel diameter and minimal lumen diameter (MLD) were 2.68 ± 0.48 and 0.90 ± 0.55 mm for the main branch, respectively and 2.28 ± 0.34 and 1.14 ± 0.47 mm for the side branch, respectively. Postprocedure MLD was 2.56 ± 0.39 mm for the main branch and 2.16 ± 0.29 mm for the side branch. There were no in‐hospital major adverse cardiac events (MACE). At 72 days after procedure there was one case of side branch stent thrombosis (2.2%), which resulted in non Q‐wave MI. Angiographic follow up was obtained in 100% of patients at 7.5 ± 1.3 months. Target lesion revascularization (TLR) was 12.2%; no death and Q‐wave MI were observed; reference vessel diameter and MLD for the main branch were 2.79 ± 0.51 and 1.99 ± 0.65 mm respectively and for the side branch 2.28 ± 0.40 and 1.63 ± 0.48 mm respectively. Restenosis rate in the main branch was 12.2% while in the side branch was 2.0%. Conclusions: In‐hospital outcome indicates that the mini‐crush technique for bifurcation lesions with DES can be easily performed. It provides very low total MACE rate and restenosis at 8‐month follow‐up. These results confirmed the advantage of this specific technique to give complete coverage of the ostium of the side branch using two stents technique.

Transient Impairment of Vasomotion Function After Successful Chronic Total Occlusion Recanalization

OBJECTIVESnThe aim of our study was to assess coronary vasomotion after successful revascularization of chronic total occlusion (CTO).nnnBACKGROUNDnIt is largely unknown whether the recovery of anterograde flow after CTO recanalization with drug-eluting stent implantation affects vascular function in distal coronary segments.nnnMETHODSnOne hundred consecutive CTOs successfully treated with drug-eluting stents underwent coronary diameter measurement after intracoronary nitroglycerin injection 5, 20, and 35 mm distal to the stented coronary segment using 3-dimensional quantitative coronary angiography. In a subgroup of 14 patients, coronary vasomotion was tested in distal segments: incremental atrial pacing for endothelium-dependent cases; and intracoronary nitroglycerin injection for endothelium-independent cases. In another subgroup of 13 patients, distal vessels were assessed by intracoronary ultrasounds.nnnRESULTSnVessel diameters significantly increased at follow-up as compared to baseline values (2.0 ± 0.52 mm vs. 2.25 ± 0.50 mm, 1.76 ± 0.49 mm vs. 2.05 ± 0.58 mm, 1.54 ± 0.53 mm vs. 2.04 ± 0.58 mm, at each segment analyzed; p < 0.001). At baseline, distal segments failed to respond to both endothelium-dependent and -independent stimuli. At follow-up, atrial pacing induced vasoconstriction, whereas nitroglycerine administration resulted in significant vasodilation (p < 0.05). Intracoronary ultrasounds failed to show changes of the cross-sectional area of distal segments at follow-up angiography.nnnCONCLUSIONSnRecanalization of CTO is followed by a hibernation of vascular wall at distal coronary segments that fail to respond to endothelium-dependent and -independent stimuli. Distal vessel diameter increases over time in the absence of positive remodeling and in spite of persistent endothelial dysfunction. This severe impairment of vasomotor tone after CTO reopening suggests that intracoronary ultrasound assessment is of paramount importance for the selection of stent size.

Management strategies in patients affected by chronic total occlusions: results from the Italian Registry of Chronic Total Occlusions

BACKGROUNDnThrough contemporary literature, the optimal strategy to manage coronary chronic total occlusions (CTOs) remains under debate.nnnOBJECTIVESnThe aim of the Italian Registry of Chronic Total Occlusions (IRCTO) was to provide data on prevalence, characteristics, and outcome of CTO patients according to the management strategy.nnnMETHODSnThe IRCTO is a prospective real world multicentre registry enrolling patients showing at least one CTO. Clinical and angiographic data were collected independently from the therapeutic strategy [optimal medical therapy (MT), percutaneous coronary intervention (PCI), or coronary artery bypass grafting (CABG)]; a comparative 1-year clinical follow-up was performed.nnnRESULTSnA total of 1777 patients were enrolled for an overall CTO prevalence of 13.3%. The adopted therapeutic strategies were as follows: MT in 826 patients (46.5%), PCI in 776 patients (43.7%), and CABG in the remaining 175 patients (9.8%). At 1-year follow-up, patients undergoing PCI showed lower rate of major adverse cardiac and cerebrovascular events (MACCE) (2.6% vs. 8.2% and vs. 6.9%; P < 0.001 and P < 0.01) and cardiac death (1.4% vs. 4.7% and vs. 6.3%; P < 0.001 and P < 0.001) in comparison with those treated with MT and CABG, respectively. After propensity score-matching analysis, patients treated with PCI showed lower incidence of cardiac death (1.5 vs. 4.4%; P < 0.001), acute myocardial infarction (1.1 vs. 2.9%; P = 0.03), and re-hospitalization (2.3 vs. 4.4% P = 0.04) in comparison with those managed by MT.nnnCONCLUSIONSnOur data showed how CTO PCI might significantly improve the survival and decrease MACCE occurrence at 1 year follow-up in comparison with MT and/or CABG.

Appropriateness of percutaneous revascularization of coronary chronic total occlusions: an overview.

Coronary chronic total occlusions (CTOs) are commonly encountered in patients undergoing coronary angiography. Several observational studies have demonstrated that successful CTO revascularization is associated with better cardiovascular outcomes and enhanced quality of life (QOL). However, in the absence of randomized trials, its prognostic benefit for patients remains debated. Over the past decade, the interest of the interventional community in CTO percutaneous coronary intervention (PCI) has exponentially grown due to important developments in dedicated equipment and techniques, resulting in high success and low complication rates. Both European and American guidelines have assigned a class IIa (level of evidence B) recommendation for CTO PCI. In the current review, we focus on the impact of CTO revascularization on clinical outcomes and QOL and on appropriate patient selection, and we provide a critical assessment of the current guidelines and recommendations on CTO PCI.

Mini-STAR as bail-out strategy for percutaneous coronary intervention of chronic total occlusion.

Background: Although the advancement of the equipment and the presence of innovative techniques, percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) continues to be affected by lower procedural success in comparison with non occluded vessel PCI. Objective: We describe a new technique for the treatment of coronary CTO which utilizes a new generation of polymeric wires. Methods and Result: From March 2009 to June 2010 different strategies were adopted as “bail out” after an initial attempt failed in 117 consecutive CTO lesions. Among these, conventional strategies (CS) such as parallel wire, sub‐intimal tracking and re‐entry (STAR), microchannel technique, intracoronary ultrasound guided revascularization and anchor balloon, were used in 75 cases (64.1%), while in the remaining a new technique, the “mini‐STAR,” was used (39.9%). Although no substantial differences were observed regarding the distribution of clinical features and angiographic lesions characteristics between the populations, mini‐STAR was able to achieve a higher rate of procedural success in comparison with other CS (97.6% vs. 52%, P < 0.001) with lower contrast agent use (442 ± 259 cm3 vs. 561 ± 243 cm3, P = 0.01) and shorter procedural and fluoroscopy times (122 ± 61 vs. 157 ± 74 min, P = 0.009 and 60 ± 31 min vs. 75 ± 38 min, P = 0.03, respectively). No differences were observed in term of peri‐procedural complications such as procedural myocardial infarction, coronary perforations, and contrast‐induced nephropathy between mini‐STAR and CS. Conclusion: The mini‐STAR technique is a promising strategy for the treatment of CTO lesions, achieving a high procedural success rate and low occurrence of procedural adverse events.

Cigarette Smoking Is Associated With a Dose-Response Effect in Clopidogrel-Treated Patients With Diabetes Mellitus and Coronary Artery Disease : Results of a Pharmacodynamic Study

OBJECTIVESnThis study sought to assess the presence of a dose-response effect of cigarette smoking and its impact on high on-treatment platelet reactivity (HPR) in patients with diabetes mellitus treated with clopidogrel.nnnBACKGROUNDnCigarette smoking is an inducer of cytochrome P450 1A2, a hepatic enzyme involved in clopidogrel metabolism. If cigarette smoking is associated with a dose-response effect on pharmacodynamic measures in clopidogrel-treated patients is unknown.nnnMETHODSnA total of 134 type 2 diabetes mellitus patients on maintenance aspirin and clopidogrel therapy were studied. Patients were divided into 3 groups according to cotinine levels: <3 ng/ml (nonsmokers), 3 to 199 ng/ml (light smokers), and ≥ 200 ng/ml (heavy smokers). Platelet function was assessed by light transmittance aggregometry, VerifyNow P2Y12 assay (Accumetrics, San Diego, California), and vasodilator-stimulated phosphoprotein. Rates of HPR were defined using established cutoff values.nnnRESULTSnA dose-response effect was observed for all pharmacodynamic parameters tested. Serum cotinine levels were inversely associated with platelet reactivity as assessed by light transmittance aggregometry using 5 and 20 μmol/l adenosine diphosphate (p < 0.0001 for all). Accordingly, platelet disaggregation increased with levels of serum cotinine (p < 0.0001). Similar results were found with P2Y(12) reaction units (p < 0.0001) and inhibition of platelet aggregation (p = 0.005) as defined by VerifyNow P2Y12 testing, and platelet reactivity index (p = 0.002) as assessed by vasodilator-stimulated phosphoprotein. Higher serum cotinine levels were significantly associated with lower rates of HPR, as defined according to various pharmacodynamic cutoff measures.nnnCONCLUSIONSnCigarette smoking is associated with a dose-response effect on clopidogrel-induced antiplatelet effects and lower rates of HPR in diabetes mellitus patients.