This review summarizes the most recent developments in providing advanced supportive measures for cardiopulmonary resuscitation, and the results obtained using these new therapies in patients with cardiac arrest caused by acute myocardial infarction (AMI). Also detailed are new approaches such as extracorporeal cardiopulmonary resuscitation (ECPR), intra-arrest percutaneous coronary intervention, or the regional models for systems of care aiming to reduce the critical times from cardiac arrest to initiation of ECPR and coronary revascularization.

Out-of-hospital cardiac arrest (OHCA) occurring as the first manifestation of an acute myocardial infarction is associated with very high mortality rates. As in comatose patients the etiology of cardiac arrest may be unclear, especially in cases without ST-segment elevation on the surface electrocardiogram, the decision to perform or not to perform urgent coronary angiography can have a significant impact on the prognosis of these patients. This review summarises the current knowledge and recommendations for treating patients with acute myocardial infarction presenting with OHCA. New therapeutic measures for the post-resuscitation phase are presented, such as hypothermia or extracardiac life support, together with strategies aiming to restore the coronary flow in the resuscitation phase using intra-arrest percutaneous revascularization performed during resuscitation. The role of regional networks in providing rapid access to the hospital facilities and to a catheterization laboratory for these critical cardiovascular emergencies is described.

Cost‐effectiveness of percutaneous coronary intervention (PCI) using drug‐eluting stents (DES), and coronary artery bypass surgery (CABG) was analyzed in patients with multivessel coronary artery disease over a 5‐year follow‐up.

BACKGROUND AND AIM OF THE STUDY:Restenosis occurs invariably within 12 months following balloon valvuloplasty (BAV) in calcific aortic valve disease (CAVD), and is a limiting factor of this treatment. Cellular proliferation secondary to balloon injury is thought to play a pivotal role in the mechanism of restenosis. The study aim was to investigate the potential role of a paclitaxel-eluting valvuloplasty balloon to mitigate the progression of restenosis in an animal model of CAVD.METHODS:Fifty-three rabbits were fed with an aortic stenosis (AS)-inducing diet (cholesterol 0.5% plus vitamin D3 50,000 IU/day) for three months. The surviving animals (n = 40) underwent echocardiographic and invasive assessments, followed by valvuloplasty, randomly using either a paclitaxel-coated (3 μg/mm2) or a plain balloon. At one month after BAV, the surviving animals (n = 28) underwent repeat assessments, followed by histology and micro-computed tomography (MicroCT) analysis of the aortic valve.RESULTS:The baseline and post-BAV transvalvular gradients, aortic valve area (AVA), left ventricular stroke work loss (SWL) and aortic valve resistance (AVR) were similar between the groups (14 rabbits were assigned to paclitaxel-eluting, and 14 to plain balloon). Significant differences between the groups were observed at one-month post-BAV, which was suggestive of diminished restenosis in the paclitaxel-balloon group (mean maximum transvalvular pressure gradient 7.7 ± 7.7 versus 3.6 ± 3.7 mmHg, p = 0.08; AVA 0.91 ± 0.59 versus 0.55 ± 0.22 cm2, p = 0.04; SWL 3.5 ± 4.0 versus 8.6 ± 8.0%, p = 0.047; AVR 86 ± 71 versus 177 ± 137 dynes/s/cm(-5), p = 0.039). Histology demonstrated decreased leaflet thickness (0.60 ± 0.15 versus 0.71 ± 0.17 mm, p = 0.03), proliferating cell nuclear antigen (PCNA) staining (grade 1.53 ± 0.04 versus 2.24 ± 0.55, p = 0.049), and calcification in the paclitaxel-balloon group.CONCLUSION:Use of a paclitaxel-eluting valvuloplasty balloon in an animal model of AS resulted in attenuated restenosis, secondary to decrease in valve proliferation and calcification.

Cost-effectiveness of percutaneous coronary intervention (PCI) using drug-eluting stents (DES) was compared to the costs of coronary artery bypass surgery (CABG) in patients with multivessel coronary artery disease in the first 5 years follow-up (FUP). 199 patients with multivessel DES-PCI (n=114,

Objectives This study evaluated the protective effect of nitric oxide-coating of introducer sheath on the local complications in juvenile porcine femoral arteries with similar size to human radial arteries.Background Insertion of an introducer sheath induces vasospasm and transient or permanent vessel occlusion of radial arteries.Methods Nitric oxide-coated or control introducer sheaths with or without spasmolytic cocktail (control + C-sheath) were inserted into porcine femoral arteries, followed by percutaneous coronary intervention (PCI). The diameter of the femoral artery at the puncture site, distally and proximally, was measured by quantitative angiography. Histopathological and histomorphometric parameters of the femoral arteries were analyzed 1 h or 1 week after PCI.Results Insertion of femoral sheath led to mild or severe spasms, with significantly higher vessel diameter at the access site (2.69 +/- 0.81 mm vs. 1.77 +/- 0.77 mm and 1.85 +/- 0.66 mm, p < 0.001), and proximal and distal to it, during PCI in the nitric oxide-sheath group versus the control-sheath and control + C-sheath groups, respectively. Immediately following PCI, significantly less lumina! thrombosis (12% vs. 33% and 31% of all analyzed segments, p < 0.001) was observed in the nitric oxide-sheath arteries. At 1 week, lower intimal inflammation score (0.43 +/- 11 vs. 1.03 +/- 0.35 and 1.04 +/- 0.32, p < 0.05), less luminal thrombosis (8% vs. 21% and 30% p < 0.05), and smaller intimal hyperplasia (0.31 +/- 0.31 mm(2) vs. 0.47 +/- 1.00 mm(2) and 0.86 +/- 0.82 mm(2), p < 0.05) were observed in NO-sheath arteries at the injury site.Conclusions Nitric oxide coating on the introducer sheath prevents local complications during PCI and results in less vascular thrombosis and inflammation at the access site, contributing to patency of the access vessel with similar size to the radial artery. (J Am Coll Cardiol Intv 2011;4:98-106) (C) 2011 by the American College of Cardiology Foundation

AIMS:Genes encoding vascular endothelial growth factor (VEGF) can potentially augment myocardial perfusion in patients with coronary artery disease (CAD). We conducted a randomised, double-blind, placebo-controlled gene therapy study with the adenovirus carrying VEGF121 (BIOBYPASS [AdGVVEGF121.10NH]).METHODS AND RESULTS:Seventeen patients with severe CAD were 2:1 randomised to BIOBYPASS (n=12; 61 years) or placebo (n=5; 64) as 12 intra-myocardial injections into the ischaemic area using the NOGA XP® system. The study was terminated prematurely due to a company product portfolio decision. Mean change in total exercise duration from baseline to 12, 26 and 52 weeks was 20.2, 21.4 and 16.4 sec in BIOBYPASS treated and 46.2, 31.4 and 12.4 sec in placebo (NS). Change from baseline to at least 1 mm ST depression during exercise at 12, 26 and 52 weeks did not differ between BIOBYPASS and placebo. Change in stress-induced ischaemia score was similar in the BIOBYPASS (3.4%) and placebo (2.0%) groups. An improvement in symptoms was seen in patients treated with BIOBYPASS, but no difference between the groups.CONCLUSIONS:Direct intramyocardial injection of BIOBYPASS (AdGVVEGF121.10NH) was safe but did not improve exercise capacity, time to ischaemic threshold or myocardial perfusion compared to sham injection in patients with refractory myocardial ischaemia.

PURPOSE:To evaluate the development of neointimal hyperplasia after implantation of drug-eluting stents (paclitaxel) compared to bare metal stents in porcine internal carotid arteries (ICAs).METHODS:While drug-eluting stents have effectively reduced neointimal proliferation in porcine external carotid arteries, the porcine internal carotid artery (ICA) is more sensitive to shear stress and altered flow conditions. Thus, a study was conducted to evaluate bare vs. drug-eluting stents in porcine ICAs. Under general anesthesia, 18 domestic pigs were implanted with paclitaxel-eluting (n = 18) and bare (n = 18) stents in the left and right ICAs, respectively. After 1 and 3 months, control carotid angiography was performed, followed by histopathological and histomorphometric analyses of the stented ICA.RESULTS:Histopathological results (fibrin deposition, necrosis, inflammation) were similar in the groups at 1 and 3 months. Moreover, the injury score and rate of endothelialization did not differ between the groups. Histomorphometric analysis after 1 month revealed significantly (p<0.05) less neointimal hyperplasia after implantation of paclitaxel-eluting stents. The antiproliferative effect of paclitaxel-eluting stents were maintained during the 3-month follow-up: the neointimal area was 0.7 ± 0.5 vs. 1.2 ± 0.6 mm(2) (p<0.01), the area stenosis was 23.5% ± 13.9% vs. 37.8% ± 14.4% (p<0.01), the maximal neointimal thickness was 0.2 ± 0.1 vs. 0.2 ± 0.9 mm (p<0.05) in paclitaxel-eluting vs. bare stents, respectively. Implantation of paclitaxel-eluting and bare stents did not lead to edge restenosis or vessel remodeling in porcine ICAs at 1 or 3 months.CONCLUSION:Compared to bare metal stents, drug-eluting stents implanted in the porcine ICA produced significantly less neointimal hyperplasia.

Summary Percutaneous coronary intervention (PCI) represents the most important treatment of coronary artery stenosis today. But instent restenosis (ISR) is a limitation for the outcome. Fas and Fas Ligand have been implicated in apoptosis and vessel wall inflammation. Their role in ISR is not known so far. In this prospective study we studied 137 patients with stable coronary artery disease who underwent elective PCI. Blood samples were taken directly before and 24 hours after PCI. Soluble (s)Fas and sFas Ligand serum levels were measured by ELISA. Restenosis was evaluated six to eight months later either by coronary angiography or by exercise testing. During the follow-up period, 18 patients (13%) developed ISR. At baseline, patients with ISR had significantly lower median sFas, as well as sFas Ligand levels compared to patients without ISR (sFAS: ISR 492 pg/ml, no ISR 967 pg/ml, p=0.014; sFAS Ligand: ISR: 26 pg/ml, no ISR: 42 pg/ml, p=0.001). After PCI median sFas levels significantly decreased in patients with ISR compared to patients without ISR [ISR: –152 pg/ml (IQR –36 to –227), no ISR: –38 pg/ml (IQR –173 to +150 pg/ml), p=0.03]. sFas Ligand levels after PCI significantly increased in ISR patients compared to patients without ISR [ISR: 14 pg/ ml (IQR –3 to +26 pg/ml), no ISR –6 pg/ml (IQR –22 to +21 pg/ml), p=0.014]. In conclusion, sFas and sFas Ligand seem to be associated with the development of ISR. Determination of serum levels before and after PCI might help identifying patients at higher risk of ISR.

Taxus™ stent implantations with the aim of complete revascularization can be safe for patients with multivessel disease. The Austrian Multivessel Taxus Stent (AUTAX) registry including patients with post-percutaneous coronary intervention lesions provides additional information to the Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) study.

SummaryThe aim of the sub-study of the MYSTAR randomised trial was to analyse the changes in myocardial perfusion in NOGA-defined regions of interest (ROI) with intramyocardial injections of autologous bone marrow mononuclear cells (BM-MNC) using an elaborated transformation algorithm. Patients with recent first acute myocardial infarction (AMI) and left ventricular (LV) ejection fraction (EF) between 30–45% received BM-MNC by intramyocardial followed by intracoronary injection 68 ± 34 days post-AMI (pooled data of MYSTAR). NOGA-guided endocardial mapping and 99m-Sestamibi-SPECT (single photon emission computer tomography) were performed at baseline and at three months follow-up (FUP). ROI was delineated as a best polygon by connecting of injection points of NOGA polar maps. ROIs were projected onto baseline and FUP polar maps of SPECT calculating the perfusion severity of ROI. Infarct size was decreased (from 27.2 ± 10.7% to 24.1 ± 11.5%, p<0.001), and global EF increased (from 38 ± 6.1% to 41.5 ± 8.4%, p<0.001) three months after BM-MNC delivery. Analysis of ROI resulted in a significant increase in unipolar voltage (index of myocardial viability) (from 7.9 ± 3.0 mV to 9.9 ± 2.7 mV at FUP, p<0.001) and local linear shortening (index of local wall motion disturbances) (from 11.0 ± 3.9% to 12.7 ± 3.4%, p=0.01). NOGA-guided analysis of the intramyocardially treated area revealed a significantly increased tracer up-take both at rest (from 56.7 ± 16.1% to 62.9 ± 14.2%, p=0.003) and at stress (from 59.3 ± 14.2% to 62.3 ± 14.9%, p=0.01). Patients exhibiting ≥5% improvement in perfusion defect severity received a significantly higher number of intramyocardial BM-MNC. In conclusion, combined cardiac BM-MNC delivery induces significant improvement in myocardial viability and perfusion in the intramyocardially injected area.Clinical Trials Gov Nr: NCT00384982.

Background In the setting of primary percutaneous coronary intervention, patients with a chronic total occlusion in a non-infarct related artery were recently identified as a high-risk subgroup. It is unclear whether ST-elevation myocardial infarction patients with a chronic total occlusion in a non-infarct related artery should undergo additional percutaneous coronary intervention of the chronic total occlusion on top of optimal medical therapy shortly after primary percutaneous coronary intervention. Possible beneficial effects include reduction in adverse left ventricular remodeling and preservation of global left ventricular function and improved clinical outcome during future coronary events. Methods/Design The Evaluating Xience V and left ventricular function in Percutaneous coronary intervention on occLusiOns afteR ST-Elevation myocardial infarction (EXPLORE) trial is a randomized, prospective, multicenter, two-arm trial with blinded evaluation of endpoints. Three hundred patients after primary percutaneous coronary intervention for ST-elevation myocardial infarction with a chronic total occlusion in a non-infarct related artery are randomized to either elective percutaneous coronary intervention of the chronic total occlusion within seven days or standard medical treatment. When assigned to the invasive arm, an everolimus-eluting coronary stent is used. Primary endpoints are left ventricular ejection fraction and left ventricular end-diastolic volume assessed by cardiac Magnetic Resonance Imaging at four months. Clinical follow-up will continue until five years. Discussion The ongoing EXPLORE trial is the first randomized clinical trial powered to investigate whether recanalization of a chronic total occlusion in a non-infarct related artery after primary percutaneous coronary intervention for ST-elevation myocardial infarction results in a better preserved residual left ventricular ejection fraction, reduced end-diastolic volume and enhanced clinical outcome. Trial registration trialregister.nl NTR1108.

SummaryEffects of ischaemic preconditioning (IP) on the mobilisation and recruitment of haematopoietic (HSCs) and mesenchymal stem (MSC) cells were determined in porcine coronary occlusion/reperfusion. Thirtythree pigs underwent percutaneous occlusion of the left anterior descending coronary artery (LAD) for 90 minutes (min), followed by 120 min reperfusion. IP was performed in 16 of the 33 pigs by two cycles of 5 min balloon occlusion/reperfusion prior to the 90 min occlusion (group IP vs. group C). Peripheral blood and myocardial tissue concentration of bone marrow origin HSCs (characterised by coexpression of CD31+, CD90+, CD45+) and MSCs (characterised by coexpression of CD44+, CD90+, CD45-) were measured by flow cytometry in the early phase of IP. Plasma/serum levels of stem cell mobilisation factors (stromal cell-derived factor-1α [SDF-1α], vascular endothelial growth factor [VEGF], tumour necrosis factor α[TNF-α] and interleukin-8 [IL-8]) were measured. IP led to a significant increase in circulating HSCs as compared with the group C (475 ± 233 vs. 281 ± 264 /μl, p=0.032) in the early phase of IP. In contrast, a rapid and prolonged decrease in level of circulating MSCs was observed in group IP as compared with group C (19 ± 12 vs. 32 ± 17 /μl, p=0.015). The recruitment of HSCs and MSCs in infarct and border zone was significantly greater in IP group, indicating a faster homing of MSCs as compared with the rate of mobilisation. Rapid increase in VEGF, TNF-α and IL-8 levels was induced by IP, which, however, was not correlated with the levels of circulating SCs. In conclusion, IP resulted in differential mobilisation and recruitment of HSCs and MSCs in the early phase of cardioprotection.