MISSION!: optimization of acute and chronic care for patients with acute myocardial infarction.

BACKGROUND: Guideline implementation programs for patients with acute myocardial infarction (AMI) enhance adherence to evidence-based medicine (EBM) and improve clinical outcome. Although undertreatment of patients with AMI is well recognized in both acute and chronic phases of care, most implementation programs focus on acute and secondary prevention strategies during the index hospitalization phase only. HYPOTHESIS: Implementation of an all-phase integrated AMI care program maximizes EBM in daily practice and improves the care for patients with AMI. AIM: The objective of this study is to assess the effects of the MISSION! program on adherence to EBM for patients with AMI by the use of performance indicators. DESIGN: The MISSION! protocol is based on the most recent American College of Cardiology/American Heart Association and European Society of Cardiology guidelines for patients with AMI. It contains a prehospital, inhospital, and outpatient clinical framework for decision making and treatment, up to 1 year after the index event. MISSION! concentrates on rapid AMI diagnosis and early reperfusion, followed by active lifestyle improvement and structured medical therapy. Because MISSION! covers both acute and chronic AMI phase, this design implies an intensive multidisciplinary collaboration among all regional health care providers. CONCLUSION: Continuum of care for patients with AMI is warranted to take full advantage of EBM in day-to-day practice. This manuscript describes the rationale, design, and preliminary results of MISSION!, an all-phase integrated AMI care program.

Role of calcified spots detected by intravascular ultrasound in patients with ST-segment elevation acute myocardial infarction.

Electron beam computed tomographic studies have demonstrated that the extent of intracoronary calcium is related to risk of coronary events. This study was performed to gain further insight into the distribution of focal calcifications and their relation to the site of plaque rupture within the culprit artery in consecutive patients (n = 60) with acute myocardial infarction (AMI) using intravascular ultrasound imaging. Calcifications in the culprit lesion and adjacent segments were classified and counted according to their arc (< 45 degrees, 45 degrees to 90 degrees, 90 degrees to 180 degrees, > 180 degrees), length (< 1.5, 1.5 to 3.0, 3.0 to 6.0, > 6.0 mm), and dispersion (number of spots per millimeter). Calcifications at the edge of a visible rupture or ulceration were considered related to the AMI. Compared with adjacent proximal and distal segments, the culprit lesion contained more calcified spots per millimeter (0.14, 0.10, and 0.21, respectively, p < 0.05). Small calcified spots (arc < 45 degrees, length < 1.5 mm) were more common (p < 0.05). Plaque rupture or ulceration was manifest in 31 culprit lesions (52%), 14 (45%) of which contained focal calcifications. These calcified spots extended more often to 90 degrees to 180 degrees of the vessel circumference and were more often of moderate length (3 to 6 mm) compared with culprit lesions without visible plaque rupture (p < 0.05). In conclusion, culprit lesions in patients with AMI contain more and smaller calcifications compared with adjacent segments. Calcifications related to plaque rupture appear to be larger and extend over a wider arc compared with these calcified spots. Those larger calcified spots may play a role in plaque instability in a subgroup of lesions.

Histopathologic alterations following local delivery of dexamethasone to inhibit restenosis in murine arteries.

OBJECTIVE: Dexamethasone-eluting stents are currently under evaluation to prevent post-angioplasty restenosis. The efficacy and safety of dexamethasone as an anti-restenotic agent is still unclear. We assess the effect of perivascular delivery of dexamethasone on vascular pathology in a mouse model of restenosis. METHODS AND RESULTS: In this study we investigate the ability of both systemic and local dexamethasone treatment to inhibit neointima formation after cuff placement around C57BL/6 mouse femoral artery. As in the clinical situation, systemic dexamethasone treatment shows adverse side effects in animals, including weight loss. In contrast, local delivery of dexamethasone using a drug-eluting polymer cuff inhibits neointima formation and has no systemic adverse effects. Pathobiological examination of the experimental arteries, however, reveals a dose-dependent medial atrophy, a reduction in vascular smooth muscle cells and collagen content, an increase in apoptotic cell count and disruption of the internal elastic lamina. CONCLUSIONS: Our results demonstrate that although local dexamethasone delivery is effective as an inhibitor for neointima formation, it is dose-dependently associated with adverse vascular morphological changes pointing to a loss of vascular integrity.

Local perivascular delivery of anti-restenotic agents from a drug-eluting poly(epsilon-caprolactone) stent cuff.

The introduction of drug-eluting stents (DES) to prevent in-stent restenosis is one of the major advances in interventional cardiology. Currently many types of DES are under evaluation for effectiveness and safety, a time-consuming and difficult procedure in humans. An animal model that allows rapid evaluation of the present and upcoming therapeutic approaches to prevent in-stent restenosis is most valuable and still lacking. Here, a perivascular cuff to induce restenosis was constructed of a poly(epsilon-caprolactone) (PCL) formulation suitable for the controlled delivery of drugs. Placing the PCL cuff around the femoral artery, in vivo, resulted in reproducible restenosis-like lesions containing predominantly smooth muscle-actin positive cells. Loading the cuff with the anti-restenotic compounds paclitaxel and rapamycin resulted, in vitro, in a sustained and dose-dependent release for at least 3 weeks. Paclitaxel- and rapamycin-eluting PCL cuffs placed around the femoral artery of mice in vivo significantly reduced intimal thickening by 76 +/- 2% and 75 +/- 6%, respectively, at 21 days. Perivascular sustained release of both anti-restenotic agents is restricted to the cuffed vessel segment with no systemic adverse effects or effect on cuffed contralateral femoral arteries. Drug-eluting PCL cuffs provide an easy and rapid tool to evaluate anti-restenotic agents to be used in combination with the DES strategies.

Drug-eluting stents: results, promises and problems.

In-stent restenosis is the major drawback of percutaneous coronary interventions, occurring in 10-40% of the patients. Recently, new stents have emerged which are loaded with anti-inflammatory, anti-migratory, anti-proliferative or pro-healing drugs. These drugs are supposed to inhibit inflammation and neointimal growth and subsequently in-stent restenosis. In this review article the results of human clinical studies investigating drug-eluting stents are discussed from a clinical point of view, focussing on the efficacy in the prevention of restenosis and their potential side effects. Both success and failure in the field of drug-eluting stents have been described. Successful devices are the sirolimus-eluting and the polymer-based paclitaxel-eluting stents. Potentially dangerous side effects of drug-eluting stents are adverse drug interactions, incomplete stent apposition and increased in-stent thrombosis rates. Demonstration of long-term efficacy is mandatory since in some animal studies a delayed healing has been observed. Currently, the successful drug-eluting stents are under investigation in all types of lesions. We conclude that the results with some drug-eluting stents are promising, but further evidence on long-term efficacy and safety, also in high-risk subgroups, is needed.

Evaluation of patients with previous coronary stent implantation with 64-section CT.

PURPOSE: To prospectively evaluate the diagnostic accuracy of 64-section computed tomography (CT) for the assessment of in-stent or peristent restenosis, with conventional coronary angiography as the reference standard. MATERIALS AND METHODS: The study was approved by the medical ethics committee, and informed consent was obtained in all 50 enrolled patients (40 men, 10 women; mean age, 60 years +/- 11 [standard deviation]). In addition to conventional coronary angiography with quantitative coronary angiography, 64-section CT was performed. For each stent, assessability was determined and was related to stent characteristics and heart rate by using a chi(2) test. On the interpretable images of stents and peristent lumina (5.00 mm proximal and distal to the stent), the presence of significant (> or =50%) restenosis was determined. For this analysis, partially overlapping stents were considered to represent a single stent. RESULTS: Of 76 stents, 65 (86%) were determined to be assessable. Increased heart rate and overlapping positioning were associated with increased uninterpretability of the images of stents (P < .05), whereas location of the stent and thickness of the strut were not. In seven patients, stents were placed in an overlapping manner, resulting in 58 stents available for the evaluation of significant (> or =50%) in-stent restenosis. All six significant (> or =50%) in-stent restenoses were detected, and the absence of significant (> or =50%) restenosis was correctly identified in the 52 remaining stents, resulting in sensitivity and specificity of 100%. Sensitivity and specificity for the detection of significant (> or =50%) peristent stenosis were 100% and 98%, respectively. CONCLUSION: In selected patients with previous stent implantation, 64-section CT can be used to evaluate in-stent restenosis with high accuracy. Accordingly, the technique may be useful for noninvasive exclusion of in-stent or peristent restenosis, thereby avoiding invasive imaging in a considerable number of patients.