Corrado Lettieri

Randomized Study of the Crush Technique Versus Provisional Side-Branch Stenting in True Coronary Bifurcations The CACTUS (Coronary Bifurcations: Application of the Crushing Technique Using Sirolimus-Eluting Stents) Study

Background— Sirolimus-eluting stents have been reported to be effective in the treatment of coronary bifurcations. Still, it has not been fully clarified which strategy would provide the best results with true bifurcation lesions. Methods and Results— The CACTUS trial (Coronary bifurcations: Application of the Crushing Technique Using Sirolimus-eluting stents) is a prospective, randomized, multicenter study comparing 2 different techniques of stenting, with mandatory final kissing-balloon inflation, in true bifurcations: (1) elective “crush” stenting and (2) stenting of only the main branch, with provisional side-branch T-stenting. From August 2004 to June 2007, 350 patients were enrolled in 12 European centers. The primary angiographic end point was the in-segment restenosis rate, and the primary clinical end point was the occurrence of major adverse cardiac events (cardiac death, myocardial infarction, or target-vessel revascularization) at 6 months. At 6 months, angiographic restenosis rates were not different between the crush group (4.6% and 13.2% in the main branch and side branch, respectively) and the provisional stenting group (6.7% and 14.7% in the main branch and side branch, respectively; P=NS). Additional stenting on the side branch in the provisional stenting group was required in 31% of lesions. Rates of major adverse cardiac events were also similar in the 2 groups (15.8% in the crush group versus 15% in the provisional stenting group, P=NS). Conclusions— In most bifurcations with a significant stenosis in both branches, a provisional strategy of stenting the main branch only is effective, with the need to implant a second stent on the side branch occurring in approximately one third of cases. The implantation of 2 stents does not appear to be associated with a higher incidence of adverse events at 6 months.

Emergency percutaneous coronary intervention in patients with ST-elevation myocardial infarction complicated by out-of-hospital cardiac arrest: Early and medium-term outcome

BACKGROUND The role of emergency reperfusion therapy in patients with ST-elevation myocardial infarction (STEMI) resuscitated after an out-of-hospital cardiac arrest (OHCA) has not been clearly established yet. The aim of this study was to evaluate the in-hospital and postdischarge outcomes of STEMI patients surviving OHCA and undergoing emergency angioplasty (percutaneous coronary intervention [PCI]) within an established regional network. METHODS We prospectively collected data on 2,617 consecutive patients with STEMI treated with emergency PCI in 2005; in-hospital and 6-month outcomes of 99 patients who had experienced OHCA were compared with those of 2,518 patients without OHCA. The OHCA patients also underwent a cerebral performance evaluation after 12 months. RESULTS OHCA patients were at higher clinical risk at presentation (cardiogenic shock 26% vs 5%, P < .0001). Percutaneous coronary intervention was successful in 80% of the OHCA and 89% of the non-OHCA patients (P = NS). In-hospital mortality rates were 22% and 3%, respectively (P < .0001). Independent predictors of in-hospital mortality among OHCA patients were longer delay between the call to the emergency medical system and the start of cardiopulmonary resuscitation (odds ratio [OR] 3.5, P = .03), nonshockable initial rhythms (OR 10.5, P = .002), cardiogenic shock (OR 3.05, P = .035), and a Glasgow Coma Scale score of 3 on admission (OR 2.9, P = .032). The 6-month composite rate of death, myocardial infarction, and revascularization among OHCA patients surviving the acute phase was comparable to that of non-OHCA patients (16% vs 13.9%, P = NS), and 87% of them showed a favorable neurologic recovery after 1 year. CONCLUSIONS Resuscitated OHCA patients undergoing emergency PCI for STEMI have worse clinical presentation and higher in-hospital mortality compared to those without OHCA. However, subsequent cardiac events are similar, and neurologic recovery is more favorable than reported in most previous series.

Management and Long-Term Prognosis of Spontaneous Coronary Artery Dissection

The optimal management and short- and long-term prognoses of spontaneous coronary artery dissection (SCAD) remain not well defined. The aim of this observational multicenter study was to assess long-term clinical outcomes in patients with SCAD. In-hospital and long-term outcomes were assessed in 134 patients with documented SCAD, as well as the clinical impact and predictors of a conservative rather than a revascularization strategy of treatment. The mean age was 52 ± 11, years and 81% of patients were female. SCAD presented as an acute coronary syndromes in 93% of patients. A conservative strategy was performed in 58% of patients and revascularization in 42%. On multivariate analysis, distal versus proximal or mid location of dissection (odds ratio 9.27) and basal Thrombolysis In Myocardial Infarction (TIMI) flow grade 2 or 3 versus 0 or 1 (odds ratio 0.20) were independent predictors of conservative versus revascularization strategy. A conservative strategy was associated with better in-hospital outcomes compared with revascularization (rates of major adverse cardiac events 3.8% and 16.1%, respectively, p = 0.028); however, no significant differences were observed in the long-term outcomes. In conclusion, in this large observational study of patients with SCAD, angiographic features significantly influenced the treatment strategy, providing an excellent short- and long-term prognosis.

Comparison of effectiveness and safety of sirolimus-eluting stents versus bare-metal stents in patients with diabetes mellitus (from the Italian Multicenter Randomized DESSERT Study).

Few studies directly compared drug-eluting stents and bare-metal stents (BMSs) in diabetic patients. DESSERT was an Italian multicenter randomized trial to show the efficacy of sirolimus-eluting stents (SESs) compared with BMSs in de novo lesions of diabetic patients treated with insulin and/or oral antidiabetics for > or =3 months on top of glycoprotein IIb/IIIa inhibitors. The primary end point was in-stent late lumen loss, assessed using centralized quantitative coronary angiography at 8-month follow-up. Centrally adjudicated composite major adverse cardiac events (MACEs) and target-vessel failure (TVF; death, treated vessel-related acute myocardial infarction, and target-vessel revascularization) at 30 days and 9 and 12 months were secondary end points. Seventy-five patients were randomly assigned to an SES (109 lesions), and 75 (109 lesions), to a BMS. The 2 groups were well balanced for clinical, anatomic, and procedural characteristics. In-stent late lumen loss decreased from 0.96 +/- 0.61 mm for BMSs to 0.14 +/- 0.33 for SESs (p <0.001), and in-segment binary restenosis was 38.8% versus 3.6%, respectively (p <0.001). Twelve-month clinical events were significantly lower in the sirolimus group: MACEs 22.1% versus 40% (p = 0.023), target-lesion revascularization 5.9% versus 30% (p <0.001), and TVF 14.7% versus 34.3% (p = 0.008). At multivariate analysis, stent type was confirmed as an independent predictor of in-segment late loss (p <0.001), binary restenosis (p <0.001), 12-month TVF (p = 0.010), and 12-month MACEs (p = 0.037). In conclusion, the randomized DESSERT showed SESs to be safe and effective in decreasing both angiographic parameters of restenosis and incidence of MACEs compared with BMSs in diabetic patients with de novo 1- or 2-vessel coronary stenoses.

Perioperative management of antiplatelet therapy in patients with coronary stents undergoing cardiac and non-cardiac surgery: a consensus document from Italian cardiological, surgical and anaesthesiological societies

Optimal perioperative antiplatelet therapy in patients with coronary stents undergoing surgery still remains poorly defined and a matter of debate among cardiologists, surgeons and anaesthesiologists. Surgery represents one of the most common reasons for premature antiplatelet therapy discontinuation, which is associated with a significant increase in mortality and major adverse cardiac events, in particular stent thrombosis. Clinical practice guidelines provide little support with regard to managing antiplatelet therapy in the perioperative phase in the case of patients with non-deferrable surgical interventions and/or high haemorrhagic risk. Moreover, a standard definition of ischaemic and haemorrhagic risk has never been determined. Finally, recommendations shared by cardiologists, surgeons and anaesthesiologists are lacking. The present consensus document provides practical recommendations on the perioperative management of antiplatelet therapy in patients with coronary stents undergoing surgery. Cardiologists, surgeons and anaesthesiologists have contributed equally to its creation. On the basis of clinical and angiographic data, the individual thrombotic risk has been defined. All surgical interventions have been classified according to their inherent haemorrhagic risk. A consensus on the optimal antiplatelet regimen in the perioperative phase has been reached on the basis of the ischaemic and haemorrhagic risk. Aspirin should be continued perioperatively in the majority of surgical operations, whereas dual antiplatelet therapy should not be withdrawn for surgery in the case of low bleeding risk. In selected patients at high risk for both bleeding and ischaemic events, when oral antiplatelet therapy withdrawal is required, perioperative treatment with short-acting intravenous glycoprotein IIb/IIIa inhibitors (tirofiban or eptifibatide) should be taken into consideration.

Impact of prehospital diagnosis in the management of ST elevation myocardial infarction in the era of primary percutaneous coronary intervention: reduction of treatment delay and mortality.

Objectives The aim of the study is to assess, as primary endpoints, in-hospital mortality and percutaneous coronary intervention (PCI) mortality and to compare the outcome in ST elevation myocardial infarction (STEMI) patients with different pathways to a catheterization laboratory in the context of an area with 24 h availability of catheter facilities. Methods Three hundred and ninety-nine STEMI patients, referred to an interventional centre for primary PCI, were divided into two groups according to the different pathways to the catheterization laboratory. Group A had 263 patients diagnosed following admission to First Aid. Group B had 136 patients diagnosed in a prehospital setting with telemedicine equipment and transferred directly to the interventional centre by advanced life support (ALS) ambulance. Results Significantly shorter treatment delay was observed in group B patients than in group A (262 ± 112 vs. 148 ± 81 min in group A vs. B, P < 0.001). A significant reduction in total mortality was observed in group B compared with group A (8.7 vs. 3% in group A vs. B, P < 0.05). After multivariate analysis, predictors of in-hospital mortality are age and Killip class (P < 0.01), different pathways to catheterization laboratory, pre-PCI TIMI flow and onset-to-balloon time (P < 0.05). Conclusion The present study shows a reduction in treatment delay and in-hospital mortality by prehospital ECG and direct referral to catheterization laboratory.

Importance and limits of pre-hospital electrocardiogram in patients with ST elevation myocardial infarction undergoing percutaneous coronary angioplasty

Background: The purpose of this study is to present data on the effects of pre-hospital electrocardiogram (PH-ECG) on the outcome of ST elevation myocardial infarction (STEMI) patients treated with percutaneous coronary angioplasty (PCI) included in a registry undertaken in the Italian region of Lombardy. Pre-hospital 12-lead electrocardiogram is recommended by current guidelines in order to achieve faster times to reperfusion in patients with STEMI. Methods: The registry includes 3901 STEMI patients who underwent primary PCI over an 18-month period. Results: Mean age was 63 ± 12 years. Admission through the emergency medical system (EMS) occurred in 1603 patients (40%): they were older, more frequently had previous MI, TIMI flow = 0 at entry and were more frequently in Killip class >1 than patients who were not admitted through the EMS. Among the patients admitted through the EMS, PH-ECG was obtained in 475 patients (12%). These patients had less frequently an anterior MI, but more frequently had absence of TIMI flow at entry than patients whose ECG was not teletransmitted. Moreover, they had a significantly shorter first medical contact-to-balloon time and a trend toward a lower 30-day death rate (5.3% vs 7.9 %, p = 0.06). However, only patients in Killip class 2–3 had a significantly lower mortality when the diagnostic ECG was transmitted, whereas no difference was found in Killip class 1 or Killip class 4 patients. Conclusions: In this registry, PH-ECG significantly decreased first medical contact-to-balloon time. Attempts to achieve faster reperfusion times should be undertaken, as this may result in improved outcome, particularly in patients with mild to moderate symptoms of heart failure.

Safety of clopidogrel and proton pump inhibitors in patients undergoing drug-eluting stent implantation.

ObjectiveA pharmacodynamic interaction between clopidogrel and proton pump inhibitors (PPIs) has been suggested, leading to reduced clopidogrel-induced platelet inhibitory effects. However, data from clinical studies are conflicting. The aim of this study was to evaluate the safety of long-term clopidogrel and PPI therapy. MethodsA total of 1328 consecutive patients (age 63±11 years; 81% male) undergoing drug-eluting stent implantation and 1-year follow-up were included. All patients were treated with a standard aspirin and clopidogrel treatment regimen for 12 months. The concomitant PPI therapy for the same duration was at the discretion of the clinical cardiologist. PPI therapy included lansoprazole (30 mg/day), pantoprazole (20 mg/day), or omeprazole (20 mg/day). At 1-year follow-up, major adverse cardiac events (MACE), defined as death, myocardial infarction (MI), acute coronary syndrome leading to hospitalization and nonfatal stroke, were recorded. All cause death, any stent thrombosis (ST), and bleeding (Thrombolysis in MI major and minor) were also assessed. ResultsLansoprazole, pantoprazole, and omeprazole were administered to 855, 178, and 125 patients, whereas 170 were not prescribed any PPI therapy. Among patients treated with PPIs, those on pantoprazole had more often prior MI, multivessel coronary artery disease, and chronic kidney disease, whereas earlier peptic ulcer was more frequent among patients treated with omeprazole. The incidence of 1-year MACE was not statistically different between patients in the PPI and no-PPI groups (7.5 vs. 5.0%; P=0.26). Similarly, 1-year rates of all cause death, ST, and Thrombolysis in MI major and minor bleedings did not significantly differ. After statistical adjustment for potential confounders, the concomitant use of clopidogrel and PPIs was not associated with the risk of 1-year MACE [odds ratio (OR) 1.54, P=0.38], death (OR: 0.97, P=0.961), and ST (OR: 1.01, P=0.998). No differences across the three PPI types were found. ConclusionThe association of clopidogrel and PPIs after drug-eluting stent implantation, prescribed on clinical judgement, seems safe.

Perioperative management of oral antiplatelet therapy and clinical outcomes in coronary stent patients undergoing surgery. Results of a multicentre registry.

The aim was to investigate the perioperative risk of ischaemic and bleeding events in patients with coronary stents undergoing cardiac and non-cardiac surgery and how these outcomes are affected by the perioperative use of oral antiplatelet therapy. This was a multicentre, retrospective, observational study conducted in patients with coronary stent(s) undergoing cardiac or non-cardiac surgery. The primary efficacy endpoint was the 30-day incidence of major adverse cardiac events (MACE), defined as the composite of cardiac death, myocardial infarction (MI) or stroke. The primary safety endpoint was the 30-day incidence of Bleeding Academic Research Consortium (BARC) bleeding ≥ 2. A total of 666 patients were included. Of these, 371 (55.7 %) discontinued their antiplatelet medication(s) (all or partly) before undergoing surgery. At 30 days, patients with perioperative discontinuation of antiplatelet therapy experienced a significantly higher incidence of MACE (7.5 % vs 0.3 %, p< 0.001), cardiac death (2.7 % vs 0.3 %, p=0.027), and MI (4.0 % vs 0 %, p< 0.001). After adjustment, peri-operative antiplatelet discontinuation was the strongest independent predictor of 30-day MACE (odds ratio [OR]=25.8, confidence interval [CI]=3.37-198, p=0.002). Perioperative aspirin (adjusted OR 0.27, 95 % CI 0.11-0.71, p=0.008) was significantly associated with a lower risk of MACE. The overall incidence of BARC ≥ 2 bleeding events at 30-days was significantly higher in patients who discontinued oral antiplatelet therapy (25.6 % vs 13.9 %, p< 0.001). However, after adjustment, antiplatelet discontinuation was not independently associated with BARC ≥ 2 bleeding. In conclusion antiplatelet discontinuation increases the 30-day risk of MACE, in patients with coronary stents undergoing cardiac and non-cardiac surgery, while not offering significant protection from BARC≥ 2 bleeding.

The no-reflow phenomenon in acute myocardial infarction after primary angioplasty: incidence, predictive factors, and long-term outcomes

Objective We evaluated the incidence and predictive factors of impaired microcirculation, defined as myocardial blush grade (MBG) 0, in patients undergoing primary angioplasty for ST-elevation myocardial infarction. Methods Since 2001, in our province a network has been operating for the treatment of ST-elevation myocardial infarction based on the use of primary angioplasty in all high-risk patients and, up to December 2005, 530 patients were treated. Core angiographic analysis was performed, and images were technically adequate to assess epicardial and myocardial perfusion rates in 530 patients. Outcomes were examined according to postprocedural myocardial blush. Results Patients with MBG 0–1 had more diabetes and previous anterior myocardial infarction, longer delay to mechanical reperfusion, higher baseline mean leukocyte count, higher baseline C-reactive protein level as well as higher in-hospital mortality. The correlation between MBG, Thrombolysis in Myocardial Infarction (TIMI) flow grade and ST-segment resolution suggests that MBG is an optimal marker of reperfusion. Conclusions Our results indicate that a fair percentage of patients with TIMI 3 flow after primary angioplasty do not show signs of effective reperfusion (MBG 0) and have a higher in-hospital mortality rate. Myocardial reperfusion after primary angioplasty, as assessed by MBG, strongly correlates with other markers of reperfusion success, including ST-segment resolution.