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N -Acetyl-Ser-Asp-Lys-Pro (AcSDKP) is a specific substrate for the N-terminal site of ACE and increases 5-fold during ACE inhibitor therapy. It is known to inhibit the proliferation of hematopoietic stem cells and has also recently been reported to inhibit the growth of cardiac fibroblasts. We investigated its mode of action in cardiac fibroblasts by assessing its influence on transforming growth factor β 1 (TGFβ1)–mediated Smad signaling. AcSDKP inhibited the proliferation of isolated cardiac fibroblasts ( P 0 /G 1 phase to S phase of the cell cycle. In cardiac fibroblasts transfected with a Smad-sensitive luciferase reporter construct, AcSDKP decreased luciferase activity by 55±9.7% ( P =0.01). Moreover, phosphorylation and nuclear translocation of Smad2 was decreased in cardiac fibroblasts treated with AcSDKP. To conclude, AcSDKP inhibits the growth of cardiac fibroblasts and also inhibits TGFβ1-stimulated phosphorylation of Smad2. Because AcSDKP increases substantially during ACE inhibitor therapy, this suggests a novel pathway independent of angiotensin II, by which ACE inhibitors can inhibit cardiac fibrosis.

Objective: Pre-hospital life-threatening ventricular tachycardia/fibrillation (VT/VF) is relatively common in the acute phase of ST-elevation myocardial infarction (STEMI). We evaluated the prognostic impact of out-of-hospital cardiac arrest (OHCA) due to VT/VF in non-selected patients with STEMI admitted for primary percutaneous coronary intervention (PCI). Methods: Prospective hospital registry was used to collect data of consecutive STEMI patients admitted to our hospital between 2005 and 2010. Patients with OHCA were identified from this registry, and their medical records were reviewed. Results: During the study period, 4653 patients were admitted with STEMI. Data regarding OHCA due to VT/VF was available in 4643 patients (99.8%). A total of 326 patients (7.0%) had OHCA due to VT/VF. Patients with OHCA were younger (60.3 ± 11.8 vs. 64.1 ± 12.9 year, p1:17.5% vs. 7.7%, pConclusion: In a large non-selected STEMI patient population admitted for primary PCI, OHCA due to VT/VF was associated with higher in-hospital mortality but did not affect the long-term prognosis.

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In patients with posterior wall myocardial infarction due to an occlusion of the circumflex coronary artery, a standard ECG does not show ST-elevation in half of the cases.Two male patients aged 55 and 52 years were admitted to our hospital because of chest pain and suspected myocardial infarction. In both patients, standard electrocardiograms (ECGs) showed no signs of ischemia. Pharmacological treatment with acetylsalicylic acid, heparin, clopidogrel and nitroglycerin did not relieve their chest pain. Echocardiography and the posterior ECG leads revealed signs of ischemia in the posterior wall. Coronary angiography revealed that the circumflex coronary artery was totally occluded in both patients. They were treated successfully by percutaneous coronary intervention.In approximately 50% of patients with myocardial infarction due to occlusion of the circumflex coronary artery, ST-segment elevation is limited or absent on the standard 12-lead ECG. These two cases emphasise that posterior ECG and echocardiography are valuable tools for detecting posterior wall infarction.

Background Glycoprotein (GP) IIb/IIIa inhibitors reduce ischemic complications in patients with non-ST-elevation acute coronary syndromes (NSTEACS) who undergo invasive procedures. However the optimal timing of therapy (upstream – at hospital admission in all patients prior to coronary catheterization, or downstream – after coronary angiography selectively in patients prior to percutaneous coronary intervention) is still debated. The aim of this meta-analysis was to compare the outcome of NSTEACS patients randomized to routine upstream versus deferred selective downstream GP IIb/IIIa inhibitors. Methods We scanned the literature from January 1990 to May 2009 to identify all randomized trials comparing upstream administration of GP IIb/IIIa inhibitors versus its downstream use in invasively managed NSTEACS. Results In 5 randomized trials a total of 9753 patients were randomized to upstream GP IIb/IIIa inhibitors therapy versus 9716 patients randomized to deferred selective downstream therapy. Upstream therapy was associated with reduced in-hospital or 30-day major adverse ischemic cardiac events (odds ratio=0.90 [95% confidence interval 0.82–0.98], p =0.02). However the risk of major bleeding was significantly higher with upstream therapy (odds ratio=1.35 [1.11–1.63], p =0.002). Combining ischemic and hemorrhagic events in a net clinical end-point showed no significant differences between the two approaches (odds ratio=1.01 [0.92–1.10], p =0.88). Conclusions In conclusion early administration of GP IIb/IIIa inhibitors in NSTEACS is associated with significant reduction in ischemic events compared to a selective deferred therapy after coronary angiography. However upstream therapy is also associated with increased bleeding complications. This approach should therefore be reserved for patients at high ischemic and/or low hemorrhagic risk.

Background— The use of upstream small-molecule glycoprotein (GP) IIb/IIIa inhibitors in non–ST-segment elevation acute coronary syndromes (NSTE ACS) has been studied in multiple randomized clinical trials. We systematically reviewed the effect of upstream GP IIb/IIIa inhibitor use in NSTE ACS as reported in published clinical trials. Methods and Results— Randomized clinical trials of upstream small-molecule GP IIb/IIIa inhibitors in NSTE ACS were identified through a PubMed and EMBASE search and were included if they contained 30-day outcome data. Odds ratios were generated from the published data and pooled by means of random effects modeling. The primary outcome measures were 30-day death and 30-day death or myocardial infarction. Primary safety measures were major bleeding and transfusion during the index hospitalization. Twelve clinical trials were included, evaluating tirofiban, eptifibatide, and lamifiban. Of these, 7 evaluated upstream GP IIb/IIIa inhibitors versus placebo (n=24 031) and 5 evaluated a strategy of upstream GP IIb/IIIa inhibitors versus upstream placebo with later provisional use at the time of percutaneous coronary intervention (n=19 643). Overall, upstream GP IIb/IIIa inhibitor use was associated with an 11% reduction in 30-day death/myocardial infarction (odds ratio [OR], 0.89; 95% confidence interval [CI], 0.83 to 0.95) but no significant mortality effect (OR, 0.93; 95% CI, 0.83 to 1.05). The risk of major bleeding was 23% higher in patients treated with upstream GP IIb/IIIa inhibitors (OR, 1.23; 95% CI, 1.02 to 1.48). Results were similar when only trials comparing upstream GP IIb/IIIa inhibitors versus placebo were considered: 30-day death/myocardial infarction (OR, 0.88; 95% CI, 0.81 to 0.95); 30-day death (OR, 0.89; 95% CI, 0.76 to 1.03); and major bleeding (OR, 1.17; 95% CI, 0.88 to 1.54). Upstream versus selective use at percutaneous coronary intervention trended toward lower 30-day death/myocardial infarction (OR, 0.91; 95% CI, 0.82 to 1.01) but had no effect on mortality (OR, 1.00; 95% CI, 0.81 to 1.23) and increased major bleeding risk by 34% (OR, 1.34; 95% CI, 1.10 to 1.63). Conclusions— In NSTE ACS, treatment with upstream small-molecule GP IIb/IIIa inhibitors provides a significant but modest ischemic benefit when compared with initial placebo. Compared with delayed, selective use at percutaneous coronary intervention, early upstream use is associated with a trend toward fewer ischemic events. However, these modest benefits are associated with an increased risk of bleeding.

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Item does not contain fulltext BACKGROUND: Diabetes mellitus contributes to the increase of cardiovascular deaths worldwide. Despite continuous treatment evolution, patients with diabetes suffering from an acute coronary syndrome still have a high morbidity and mortality. We aimed to analyze the impact of diabetes on one-year outcome in an unselected patient population with non-ST-elevation myocardial infarction (non-STEMI). METHODS: Retrospective analysis of 847 unselected patients with non-STEMI. We compared the baseline characteristics, treatment and outcome of patients versus those without diabetes. RESULTS: A total of 138 patients had diabetes (16%) and 709 (84%) had no diabetes. Patients with diabetes were older, often had hypertension, hyperlipidemia, previous myocardial infarction and Killip class >/=2 on admission. Approximately 80% of both patients, with and without diabetes, underwent diagnostic coronary angiography. Multivessel disease was more present among patients with diabetes, but patients with diabetes were treated more often conservatively. At one-year follow up rates of death and major adverse cardiac events were significantly higher in patients with diabetes compared to those without diabetes (8% vs. 3%; P=0.001 and 23% vs. 14%; P=0.008, respectively). Even after adjustment for differences in baseline characteristics, diabetes remained an independent predictor of mortality (OR: 2.25; CI95%: 1.05-3.91). CONCLUSIONS: In an unselected patient population with non-STEMI, patients with diabetes have higher risk factors on admission, less often undergo coronary revascularisation and have worse outcome at one-year follow-up. Diabetes is an independent predictor of one-year mortality in patients with non-STEMI.

Two young patients, a 23-year-old man and a 30-year-old woman, without any risk factors for coronary artery disease, apart from the woman being a smoker, were admitted to our hospital because of acute myocardial infarction (MI) due to spontaneous dissection of a coronary artery (SDCA). The first patient developed acute chest pain while playing soccer. The second patient had unspecific chest pain in the preceding four weeks and was admitted after successful resuscitation with ventricular fibrillation. Both patients were treated with primary percutaneous coronary intervention. SDCA is a rare cause of MI and sudden cardiac death with an indistinguishable presentation due to plaque rupture. The majority of cases occur in young women. It is associated with various pathophysiological mechanisms and can manifest during pregnancy, in the postpartum period, in collagen diseases, cocaine abuse, severe hypertension, smoking, oral contraceptives, heavy exercise, or vasospasm. Treatment, pharmacological or with revascularization, is based on the severity of the dissection. Patients who survive the acute phase have good long-term prognoses.

To compare the efficacy of rapamycin-eluting stents (RES) and paclitaxel-eluting stents (PES) in patients undergo percutaneous coronary intervention.RES and PES differ significantly with respect to polymer coating and antiproliferative drugs. It is not yet clear whether there are any differences between RES and PES with regard to clinical outcomes.Systematic searches were conducted of randomized, controlled trials (RCTs) comparing RES with PES in Medline and the Cochrane Database of systematic reviews. A meta-analysis was done of all available randomized studies comparing PES with RES. Information on study design, inclusion and exclusion criteria, number of patients and clinical outcomes was extracted by two investigators. Disagreements were resolved by consensus. The primary outcome was reintervention, target lesion revascularization (TLR) and target vessel revascularization (TVR). Stent restenosis, myocardial infarction (MI) and all-cause mortality were secondary endpoints.Twenty-one RCTs of RES versus PES with a total number of 10,147 patients were included in this meta-analysis. Indication for angioplasty was either acute coronary syndrome or stable angina. The mean follow-up period ranged from 6 to 24 months. The rates of TLR were 4.9% vs. 7.0%; p = 0.0009 and the rates of TVR were 5.1 vs. 8.3%; p0.001 for RES vs. PES, respectively. The incidence of stent restenosis was 3.9% for RES vs. 5.3% for PES; p = 0.004. Rates of MI and all-cause mortality were comparable.This meta-analysis demonstrates that, as compared to PES, RES seems to be associated with a lower risk of reintervention and stent restenosis. The risk of MI and all-cause death was similar between the two stents.

Background: Guidelines are mainly based upon results of randomised controlled clinical trials. However, due to low external validity of these trials, their results can not reasonably be applied to all patients in routine practice. In our hospital, all patients with ST-elevation myocardial infarction (STEMI) are eligible for inclusion in one of our ongoing trials or registries. To asses differences between patients enrolled versus not-enrolled in a trial or registry, we evaluated all patients with a discharge diagnose of STEMI during the study period. Methods: Retrospectively, individual patient data from all patients with a discharge diagnosis of STEMI between Jan 2001 and Dec 2001 were evaluated. Follow-up data were obtained until Dec 2004. Results: A total of 583 patients were discharged with a diagnosis of STEMI. About 455 (78%) patients were enrolled in one of the ongoing clinical trials or registry and 128 were not. Not-enrolled patients were significantly older; more often had a history of previous MI and had higher risk profiles. Multivariate analysis revealed that higher age was the only independent predictor for non enrolment. Not-enrolled patients were more often treated conservatively and had a higher mortality rate (36% vs. 6%, P

Despite their proven beneficial effects and inclusion in the guidelines, glycoprotein (GP) IIb/IIIA blockers are underused in daily practice in patients with non ST-segment elevation acute coronary syndrome (NSTE ACS). This study combines the data from two randomized controlled trials, comparing routine upstream versus selective down stream use of tirofiban in patients with NSTE ACS. Inclusion criteria for both studies (ELISA-1 and 2) were angina pectoris, with ST depression >1 mm and or a positive cardiac biomarkers. All patients were scheduled for coronary angiography. The primary and secondary end points for both studies were enzymatic infarct size (LDHQ48) and initial TIMI flow of the culprit lesion respectively. From August 2000 to January 2005, 273 patients were randomized to routine upstream tirofiban and 275 patients to selective down stream use of tirofiban. Selective down stream tirofiban was used in 55 patients (20%). Patients in the upstream group more often had a patent culprit lesion (65% vs. 50%, P=0.003) and a significantly smaller enzymatic infarct size, LDHQ48 median (25–75%): 125 (55–309) vs. 189 (68–504) IU/l, P=0.006 as compared to the selective down stream group. Subgroup analysis showed that routine upstream tirofiban was particularly effective in males, patients with a positive troponin on admission and in those not pretreated with clopidogrel. Routine upstream GP IIb/IIIa is mainly effective in patients with elevated troponin on admission and those not pretreated with clopidogrel. Large scale randomized trials are needed to evaluate the effect of GP IIb/IIIa blockers on top of clopidogrel pretreatment on major adverse cardiac events.

Despite data showing that time to treatment is very important in ST-elevation myocardial infarct patients, unacceptable long delays to reperfusion remain present in daily life practice. We sought to evaluate the feasibility and effect of improving logistics by early infarct diagnosis in the ambulance and immediate triage to a percutaneous coronary intervention (PCI) center performed by paramedics only without interference of a physician.In the On-TIME study, 209 patients were included after prehospital infarct diagnosis and triage in the ambulance (ambulance group, n = 209). Infarct diagnosis was made by highly trained paramedics with the help of a computerized electrocardiographic algorithm. The accuracy of diagnosis, time to treatment, left ventricular function, and clinical outcome were compared with the patients who were diagnosed and triaged at a referral non-PCI center (referred group, n = 258). Left ventricular function was assessed before discharge using a nuclear technique.Acute myocardial infarction was accurately diagnosed in 95% of patients in the ambulance group, as compared with 99% in the referred group (P = .01). The percentage of patients in whom pharmacologic pretreatment (heparin, aspirin, tirofiban, or placebo) was initiated in the ambulance within 90 minutes after the onset of symptoms was 59% in the ambulance group versus 43% in the referred group (P.01). A left ventricular ejection fraction of40% was present in 25% in the ambulance group, as compared with 38% in the referred group (P = .013). After multivariate analysis, ambulance triage was independently associated with a left ventricular ejection fraction40% and a favorable long-term clinical outcome.Early, prehospital infarct diagnosis, triage, and therapy in the ambulance with direct transportation to the nearest PCI center, performed by trained paramedics only, is feasible in 95% of patients. Ambulance triage resulted in earlier diagnosis and initiation of therapy and was independently associated with a better left ventricular function and clinical outcome, as compared with triage and transportation from a referral non-PCI center.

With great interest, we read the paper by Gyongyosi et al. 1 who describe the results of the ReoPro-BRIDGING trial. However, we feel that the study results should be interpreted with caution. The primary endpoint is the corrected TIMI frame count (CTFC) of the infarct related vessel (IRV) at initial angiography. However, the limitation of CTFC is that it can only be measured in patients with TIMI 2 flow or more, as the dye will not reach …

Objective N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a potent natural inhibitor of hematopoietic stem cell proliferation which is degraded mainly by angiotensin-converting enzyme (ACE). In vitro, Ac-SDKP inhibits collagen production by cardiac fibroblasts; while in vivo it blocks collagen deposition in the left ventricle (LV) of rats with hypertension or myocardial infarction (MI). In addition, it reportedly prevents and reverses macrophage infiltration in the LV of rats with MI. We tested the hypothesis that when Ac-SDKP is infused at doses that cause plasma concentrations similar to those observed after ACE inhibition, it mimics the anti-inflammatory and antifibrotic effects of ACE inhibitors (ACEi) in the heart, and, further, that these effects are independent of changes in blood pressure. Design and methods Rats were divided into five groups: (1) controls, (2) Ang II (750 mug/kg per day, s.c.), (3) Ang II + captopril (100 mg/kg per day in drinking water), (4) Ang II + Ac-SDKP (400 mug/kg per day, s.c.), and (5) Ang II + Ac-SDKP (800 mug/kg per day, s.c.). We measured LV cell proliferation, inflammatory cell infiltration, cytokine expression, hypertrophy and fibrosis. Results Plasma Ac-SDKP was five-fold higher in rats given ACEi and four- and ten-fold higher in rats given 400 and 800 mug/kg per day Ac-SDKP, respectively. ACEi significantly decreased Ang II-induced cell proliferation (Ki-67), LV macrophage/mast cell infiltration, transforming growth factor-beta, connective tissue growth factor and collagen deposition without affecting hypertension, LV hypertrophy or myocyte cross-sectional area, and these effects were mimicked by exogenous Ac-SDKP (400 mug/kg per day) which raised plasma Ac-SDKP to levels similar to ACEi BP was not decreased by either ACEi or Ac-SDKP. Conclusions We concluded that Ac-SDKP may be an important mediator of the anti-inflammatory and antifibrotic effects of ACEi in hypertension independent of its hemodynamic effects. (C) 2004 Lippincott Williams Wilkins.

An 86-year-old woman was admitted because of back pain, dyspnoea and fever. She also complained about general malaise and anorexia. Because of suspicion of lymphoma a CT scan of thorax and abdomen was performed. No lymphoma was obvious. However, a mycotic aneurysm of the aortic arch was visible (Fig. 1). Blood and urine cultures grew E. coli sensitive to ciprophloxacine. Fig. 1 Computed tomography of the thorax demonstrating the mycotic aneurysm of the aortic arch (focal dilatation of the aorta). Air pockets are visible, indicating gas-forming inflammation (arrow) Mycotic aneurysm is an unusual, life-threatening pathological entity that encompasses a spectrum of different types of arterial infection associated with high morbidity and mortality. Mycotic aneurysm can develop either when a new aneurysm is produced by infection of the arterial wall or when a pre-existing aneurysm becomes secondarily infected. Arterial trauma, bacterial endocarditis, impaired immunity and salmonella septicaemia are common risk factors for developing mycotic aneurysm [1]. The growth of mycotic aneurysms is rapid—several centimetres per month. The virulence of the organisms and arterial blood pressure may be responsible for such rapid enlargement [2]. Early and precise diagnosis of aortic mycotic aneurysm may be difficult especially in the early stages because of lack of specific symptoms; however, it should be suspected in patients with fever of unknown origin who have undergone any invasive procedure of the cardiovascular system. CT scanning with contrast enhancement is considered to be the method of choice for the diagnosis of a mycotic aortic aneurysm. CT features of mycotic aneurysm of the aorta include a hazy aortic wall with rupture, gas-forming inflammation around the aneurysm, and thrombus formation within a false lumen after aneurysmal rupture [3]. Management options include antibiotic therapy alone or in combination with surgical or endovascular therapy. However, as far as we know, there are no randomised trials to guide the management of mycotic aneurysm. The prognosis of patients with mycotic aneurysms is poor and depends upon the artery involved, treatments received, and underlying conditions. Some reports of aortic mycotic aneurysms document a mortality of 23 to 60%. Prognosis may be better when medical and surgical therapies are combined [4].

Purpose: Pre-hospital ventricular arrhythmia is common in the acute phase of ST-elevation myocardial infarction (STEMI). We assessed the prognostic impact of out of hospital cardiac arrest (OHCA) in a non-selected STEMI patient population treated with primary percutaneous coronary intervention (PCI). Methods: Registry database of all individual STEMI patients admitted to our hospital during 2005-2010. Patients with OHCA were identified from the register, and their medical records were reviewed. Results: During the study period 4653 patients were admitted with STEMI. Information regarding OHCA was available in 4640 patients (99.7%). A total of 326 patients (7.0%) had OHCA. Patients with OHCA were younger (60.3±11.8 vs. 64.1±12.9, p 1) 17.5% vs. 7.7%, p

Background In the present study we sought to determine the long-term prognostic value of left ventricular ejection fraction (LVEF), assessed by planar radionuclide ventriculography (PRV), after ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PPCI). Methods In total 925 patients underwent PRV for LVEF assessment after PPCI for myocardial infarction before discharge from the hospital. PRV was performed with a standard dose of 500 Mbq of 99mTc-pertechnetate. Average follow-up time was 2.5 years. Results Mean (± SD) age was 60 ± 12 years. Mean (± SD) LVEF was 45.7 ± 12.2 %. 1 year survival was 97.3 % and 3 year survival was 94.2 %. Killip class, multi vessel-disease, previous cardiovascular events, peak creatin kinase and its MB fraction, age and LVEF proved to be univariate predictors of mortality. When entered in a forward conditional Cox regression model age and LVEF were independent predictors of 1 and 3 year mortality. Conclusion LVEF assessed by PRV is a powerful independent predictor of long term mortality after PPCI for STEMI.

Coronary artery spasm (CAS) plays an important role in the pathogenesis of a wide variety of ischemic heart diseases. Several case reports have shown that CAS due to hypocalcemia can mimic myocardial infarction. However, in all these cases there were coexisting electrolyte abnormalities or other medical conditions that are risk factors for coronary spasm. We describe recurrent acute coronary syndrome in an otherwise healthy young woman without cardiac risk factors caused by coronary spasms, alternatively occurring in all three major coronary arteries.

Background The worse prognosis in patients without ST-elevation (non-STEMI) as compared to ST-elevation myocardial infarction (STEMI), may be due to treatment differences. We aimed to evaluate the differences in characteristics, treatment and outcome in patients with non-STEMI versus STEMI in an unselected patient population. Methods Individual patient data from all patients in our hospital with a discharge diagnosis of MI between Jan 2001 and Jan 2002 were evaluated. Follow-up data were obtained until December 2004. Patients were categorized according to the presenting electrocardiogram into non-STEMI or STEMI. Results A total of 824 patients were discharged with a diagnosis of MI, 29% with non-STEMI and 71% with STEMI. Patients with non-STEMI were significantly older and had a higher cardiovascular risk profile. They underwent less frequently coronary angiography and revascularization and received less often clopidogrel and ACE-inhibitor on discharge. Long-term mortality was significantly higher in the non-STEMI patients as compared to STEMI patients, 20% vs. 12%, p = 0.006, respectively. However, multivariate analysis showed that age, diabetes, hypertension and no reperfusion therapy (but not non-STEMI presentation) were independent and significant predictors of long-term mortality. Conclusion In an unselected cohort of patients discharged with MI, there were significant differences in baseline characteristics, and (invasive) treatment between STEMI and non-STEMI. Long-term mortality was also different, but this was due to differences in baseline characteristics and treatment. More aggressive treatment may improve outcome in non-STEMI patients.

Current guidelines recommend immediate revascularization in patients with ST-segment elevation acute coronary syndrome (STE-ACS). However, to date no evidence exists for optimal treatment of ACS patients with initial ST elevation but normalization of ST-segment elevation and anginal symptoms before