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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ahj.2007.04.041 Byline: Maarten J. Suttorp (a), Gerrit J. Laarman (b) Abstract: Primary intracoronary drug-eluting stent placement after the successful crossing of total coronary occlusions decreases restenosis rate at long-term follow-up compared with bare-metal stent implantation. The PRISON II trial was the first randomized study to show the safety and efficacy of sirolimus-eluting stents in patients with totally occluded native coronary arteries. The sirolimus-eluting stent is superior to the bare-metal stent in treating patients with total coronary occlusions, with significant reduction in angiographic binary in-stent and in-segment restenosis resulting in significantly reduced need for target lesion and target vessel revascularization. Whether sirolimus-eluting stents are superior to other drug-eluting stents in total coronary occlusions is unknown. In this prospective, randomized trial, sirolimus-eluting stent implantation will be compared with zotarolimus-eluting stent implantation for the treatment of total coronary occlusions. A total of 300 patients will be followed for up to 5 years with angiographic follow-up at 8 months. Quantitative coronary analysis will be performed by an independent core laboratory. The primary end point will be in-segment late luminal loss at 8 months angiographic follow-up. Author Affiliation: (a) Department of Interventional Cardiology St Antonius Hospital Nieuwegein, Nieuwegein, The Netherlands (b) Amsterdam Department of Interventional Cardiology-OLVG, Amsteradm, The Netherlands Article History: Received 22 January 2007; Accepted 22 April 2007 Article Note: (footnote) Clinical trial registration: Clinicaltrials.gov under ID number NCT00428454.

A study determines whether paclitaxel-eluting stents are superior to uncoated stents in the setting of primary percutaneous coronary intervention (PCI) in terms of the rate of serious adverse cardiac events at 1 year. Results indicate that although the use of paclitaxel-eluting stents reduces the incidence of serious adverse cardiac events at 1 year as compared with uncoated stents, the difference is not statistically significant.

Abstract: The principal therapy in patients with myocardial infarction to limit infarct size is myocardial reperfusion by mechanical or pharmacological intervention. Reperfusion has been proposed to cause myocardial injury beyond that caused by the preceding ischaemia, termed “reperfusion injury” (RI). While the precise mechanism of RI is still incompletely understood, a large number of clinical studies have been performed over the past decade targeting some of the postulated mechanisms of RI. These clinical studies were based on experimental data demonstrating significant myocardial salvage. Nevertheless, clinical benefits were absent or very limited. The purpose of this review is to provide an overview of the various strategies that inhibit RI and to discuss potential mechanisms that may contribute to the discrepancy between the promising pre-clinical data and the rather disappointing results obtained from prospective clinical trials. There are numerous differences between the experimental models and clinical studies, including the fact that experimental studies typically use abrupt occlusion and reperfusion protocols in animals with previously healthy myocardium that apparently do not predict the therapeutic efficacy of novel cardioprotective agents in a clinical setting with pre-existing progressive coronary disease, intermittent coronary occlusion, and relatively late reperfusion. However, discrepancies also exist between experimental studies. Future experimental studies of reperfusion injury should use models that mimic the clinical situation more closely. Furthermore, future large clinical trials should only be performed in cases where the drug under investigation proved to reduce RI in a series of well-designed (possibly multicenter) experimental studies and in clinical trials with predefined subgroups. [Copyright &y& Elsevier]

An abstract of the article "Increased nitrosative/oxidative stress lowers myocardial protein kinase G activity in heart failure with preserved ejection fraction" by Loek van Heerebeek and colleagues is presented.

Aims: The present study was designed to examine the five-year angiographic follow-up of MACE-free patients enrolled in the PRISON II study., Methods and Results: In the PRISON II study a total of 200 patients were randomised to either bare metal stents (BMS) or sirolimus-eluting stents (SES) after successful recanalisation of total coronary occlusions (TCO). Patients free of MACE with available angiography at six months were approached for repeated angiography at five years. The primary endpoint was in-stent very late luminal loss (VLLL) at five years. The secondary endpoint was additional late luminal loss (ALLL) between six months and five years. At five years, repeated angiography was performed in 72 patients, 50/82 (61%) in the SES group and 22/58 (38%) in the BMS group. In-stent VLLL was lower in the SES group (0.19 mm ± 0.72 vs. 0.51 mm ± 0.71, p=0.09) compared to the BMS group and in-segment VLLL was comparable in both groups (0.01 mm±0.58 vs. 0.03 mm ± 0.73, p=0.89). Late catch-up in lumen diameter was observed in the SES group with a trend towards increased ALLL compared to the BMS group (in-stent, 0.35 mm ± 0.88 vs. 0.04 mm ± 0.81, p=0.16; in-segment, 0.20 mm ± 0.74 vs. -0.05 mm ± 0.73, p=0.19)., Conclusions: At five-year angiographic follow-up, late catch-up was observed after successful recanalisation of TCOs treated with SES. Despite a late catch-up, the angiographic results of SES were superior in-stent and similar in-segment compared to BMS.

Aims: The aim of this study was to examine the five-year clinical outcome in patients enrolled in the Primary Stenting of Totally Occluded Native Coronary Arteries II (PRISON II) study., Methods and Results: Patients with totally occluded coronary arteries were randomised to either sirolimus-eluting stent (SES, n=100) or bare metal stent (BMS, n=100) implantation. At five years, patients in the SES group had significantly lower rates of target lesion revascularisation (12% vs. 30%, p=0.001), target vessel revascularisation (17% vs. 34%, p=0.009) and major adverse cardiac events (12% vs. 36%, p<0.001). There were no significant differences in death and myocardial infarction. Eight (8%) cases of stent thrombosis (seven definite and one probable; one early, one late, and six very late) were noticed in the SES group versus three cases (3%, one definite and two possible; all very late) in the BMS group (p=0.21)., Conclusions: The results of the present study show that the documented superior short-term angiographic and clinical results of SES in patients with total coronary occlusions are maintained during long-term 5-year follow-up as compared with BMS. On the other hand, there is a trend to a higher stent thrombosis rate in the SES group.

Aims: Comparison of magnetic guidewire navigation in percutaneous coronary intervention (magnetic PCI) across distal and/or complex lesions versus conventional navigation (conventional PCI)., Methods and Results: Forty-seven consecutive patients (age 61 +/- 10 yr) undergoing elective single vessel magnetic PCI for distal and/or complex lesions were matched by age and lesion location with 45 patients undergoing conventional PCI (age 63 +/- 10 yr). Technical success rate was defined as an intraluminal wire position distal to the stenosis. Procedural outcome and costs were evaluated. Baseline demographics and angiographic characteristics of the two groups were similar. The technical success rate did not differ between magnetic and conventional PCI (95.7 vs 97.8%; p = 1.00). Significantly shorter procedural and fluoroscopy time were observed for magnetic compared to conventional PCI (29.9 +/- 17.6 vs 41.1 +/- 21 min, p = 0.007; 7.5 +/- 7.3 vs 16.1 +/- 22.4 min, p = 0.02 respectively). Less contrast was used in the magnetic PCI group (58 ml/patient; P = 0.02). These advantages resulted in a mean estimated saving of 1400 euro per patient (P < 0.001). Advantages of procedural outcome were even more pronounced in the ACC/AHA lesion class C subgroup., Conclusions: Magnetic compared to conventional PCI is an attractive novel technique that proved to be feasible and safe and might be faster in distal and especially complex lesions.

Aims: This follow-up study was performed to assess the long-term effects of paclitaxel-eluting stents (PES) compared with bare-metal stents (BMS) in patients who had undergone a percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI)., Methods and Results: The PASSION trial randomly assigned 619 patients with STEMI to receive either a PES or BMS. The composite endpoint for the follow-up study was the occurrence of the combination of cardiac death, recurrent myocardial infarction, target lesion revascularisation (TLR) or stent thrombosis at two years. A trend towards a lower rate of the composite endpoint was observed in the PES compared to the BMS group (hazard ratio [HR] 0.70; 95% C.I. 0.45-1.09). This was driven by a reduced TLR in favour of PES (HR 0.60; 95% C.I. 0.34-1.09). Angiographically proven stent thrombosis at two years did not differ significantly between groups (2.1% in the PES group versus 1.4%; HR 1.48; 95% C.I. 0.42-5.23)., Conclusions: PES implantation for STEMI did not significantly improve clinical outcome at two years after the index event, although there was a trend towards a lower rate of target-lesion revascularisation. The rate of stent thrombosis did not differ significantly between groups.

Background: Excessive diastolic left ventricular stiffness is an important contributor to heart failure in patients with diabetes mellitus. Diabetes is presumed to increase stiffness through myocardial deposition of collagen and advanced glycation end products (AGEs). Cardiomyocyte resting tension also elevates stiffness, especially in heart failure with normal left ventricular ejection fraction (LVEF). The contribution to diastolic stiffness of fibrosis, AGEs, and cardiomyocyte resting tension was assessed in diabetic heart failure patients with normal or reduced LVEF., Methods and Results: Left ventricular endomyocardial biopsy samples were procured in 28 patients with normal LVEF and 36 patients with reduced LVEF, all without coronary artery disease. Sixteen patients with normal LVEF and 10 with reduced LVEF had diabetes mellitus. Biopsy samples were used for quantification of collagen and AGEs and for isolation of cardiomyocytes to measure resting tension. Diabetic heart failure patients had higher diastolic left ventricular stiffness irrespective of LVEF. Diabetes mellitus increased the myocardial collagen volume fraction only in patients with reduced LVEF (from 14.6+/-1.0% to 22.4+/-2.2%, P<0.001) and increased cardiomyocyte resting tension only in patients with normal LVEF (from 5.1+/-0.7 to 8.5+/-0.9 kN/m2, P=0.006). Diabetes increased myocardial AGE deposition in patients with reduced LVEF (from 8.8+/-2.5 to 24.1+/-3.8 score/mm2; P=0.005) and less so in patients with normal LVEF (from 8.2+/-2.5 to 15.7+/-2.7 score/mm2, P=NS)., Conclusions: Mechanisms responsible for the increased diastolic stiffness of the diabetic heart differ in heart failure with reduced and normal LVEF: Fibrosis and AGEs are more important when LVEF is reduced, whereas cardiomyocyte resting tension is more important when LVEF is normal.

Background: To support the clinical distinction between systolic heart failure (SHF) and diastolic heart failure (DHF), left ventricular (LV) myocardial structure and function were compared in LV endomyocardial biopsy samples of patients with systolic and diastolic heart failure., Methods and Results: Patients hospitalized for worsening heart failure were classified as having SHF (n=22; LV ejection fraction (EF) 34+/-2%) or DHF (n=22; LVEF 62+/-2%). No patient had coronary artery disease or biopsy evidence of infiltrative or inflammatory myocardial disease. More DHF patients had a history of arterial hypertension and were obese. Biopsy samples were analyzed with histomorphometry and electron microscopy. Single cardiomyocytes were isolated from the samples, stretched to a sarcomere length of 2.2 microm to measure passive force (Fpassive), and activated with calcium-containing solutions to measure total force. Cardiomyocyte diameter was higher in DHF (20.3+/-0.6 versus 15.1+/-0.4 microm, P<0.001), but collagen volume fraction was equally elevated. Myofibrillar density was lower in SHF (36+/-2% versus 46+/-2%, P<0.001). Cardiomyocytes of DHF patients had higher Fpassive (7.1+/-0.6 versus 5.3+/-0.3 kN/m2; P<0.01), but their total force was comparable. After administration of protein kinase A to the cardiomyocytes, the drop in Fpassive was larger (P<0.01) in DHF than in SHF., Conclusions: LV myocardial structure and function differ in SHF and DHF because of distinct cardiomyocyte abnormalities. These findings support the clinical separation of heart failure patients into SHF and DHF phenotypes.