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1.  Long-term clinical outcome of ST-segment elevation myocardial infarction patients with and without diabetes mellitus in the Zwolle trial 
Netherlands Heart Journal  2003;11(10):387-393.
Objectives
We sought to compare long-term survival after ST-segment elevation myocardial infarction (STEMI) in patients with and without diabetes mellitus (DM) treated with primary percutaneous coronary intervention (PCI) or thrombolytic therapy.
Background
DM is an adverse prognostic factor after STEMI. However, there is only limited information about long-term clinical outcome in STEMI patients with DM treated with PCI or thrombolysis.
Methods
Patients with STEMI (n=395) were randomised to treatment either with intravenous streptokinase or PCI. Mean follow-up was 8±2 years. We studied long-term mortality of patients with DM (n=32) and without DM (n=363) and the interaction with the treatment regimen.
Results
After eight years, a total of 17 patients with DM (53%) died compared with 88 (24%) patients without DM (OR 3.5, p<0.001). Reduced left ventricular ejection fraction (LVEF) after STEMI was more often present in patients with DM compared with patients without DM (31% vs. 15%, p=0.01). Multivariate analysis revealed that DM (OR 2.6, 95% CI 1.4-4.7, p=0.002), reduced LVEF (OR 2.4, 95% CI 1.5-3.8, p<0.001) and age ≥60 years (OR 2.4, 95% CI 1.5-3.8, p<0.001) were independent risk factors for long-term mortality. Patients with DM treated with PCI had less LVEF (13% vs. 53%, p=0.01) and lower long-term mortality rates (38% vs. 69%, p=0.08) compared with treatment with thrombolysis.
Conclusions
STEMI patients with DM are a high-risk group with higher long-term mortality rates compared with patients without DM. PCI is the treatment of choice, particularly in DM patients.
PMCID: PMC2499982
diabetes mellitus; acute myocardial infarction; angioplasty; clinical outcome; ventricular function
2.  Does a single bolus thrombolytic reduce door to needle time in a district general hospital? 
Emergency Medicine Journal : EMJ  2004;21(2):162-164.
Objectives: To answer the question "In patients presenting with ST elevation acute myocardial infarction (STEMI) and no contraindication to thrombolysis, does the introduction of Tenecteplase reduce door to needle times?"
Methods: Firstly, an observational study was performed to compare the time taken to prepare standard thrombolytic therapy with Tenecteplase. Secondly, door to needle times were compared before and after the introduction of Tenecteplase. The study was powered to be 80% sure of finding a change of 10% in the number of patients meeting the national service framework standard of a 30 minute door to needle time.
Results: Tenecteplase takes 10.5 minutes less time to prepare than standard treatment (p value <0.001). After the introduction of Tenecteplase the percentage of patients receiving thrombolysis in 30 minutes increased from 58% to 76% (p value <0.01)
Conclusion: Tenecteplase is quicker to prepare than standard therapy, resulting in a significant improvement in performance against the national service framework target.
doi:10.1136/emj.2002.003244
PMCID: PMC1726278  PMID: 14988339
3.  A successfully thrombolysed acute inferior myocardial infarction due to type A aortic dissection with lethal consequences: the importance of early cardiac echocardiography 
Thrombolysis, a standard therapy for ST elevation myocardial infarction (STEMI) in non-PCI-capable hospitals, may be catastrophic for patients with aortic dissection leading to further expansion, rupture and uncontrolled bleeding. Stanford type A aortic dissection, rarely may mimic myocardial infarction. We report a case of a patient with an inferior STEMI thrombolysed with tenecteplase and followed by clinical and electrocardiographic evidence of successful reperfusion, which was found later to be a lethal acute aortic dissection. Prognostic implications of early diagnosis applying transthoracic echocardiography (TTE) are described.
doi:10.1186/1749-8090-6-101
PMCID: PMC3174121  PMID: 21864356
4.  Reviewing time intervals from onset of the symptoms to thrombolytic therapy in patients with ST segment elevation myocardial infarction (STEMI) 
BACKGROUND:
Coronary artery diseases are one of the causes of early death all over the world. In developed countries, ischemic heart disease is responsible for half of the entire mortalities; however in developing countries it is estimated that from 9 million deaths per year, 32 percent are due to coronary artery disease. Acute coronary syndromes are responsible for over 250,000 deaths per year caused by progressive atherosclerotic process which would lead to rupture of the atherosclerotic plaque and establishing thrombosis. This study aimed to determine time intervals between the onset of the heart attack symptoms to thrombolytic therapy in patients with ST segment elevation myocardial infarction (STEMI) in selected hospitals of Isfahan University of Medical Sciences.
METHODS:
In this study, 180 subjects with first time STEMI were enrolled by categorized random sampling in cardiac care units of four hospitals affiliated to Isfahan University of Medical Sciences during 9 months. Necessary information were collected by asking the patients and reviewing their records. The data included demographic, prehospital and in-hospital data of the patients.
RESULTS:
The mean duration of time interval from the onset of heart attack symptoms to the first action in order to seek medical care was 01:16’(01:36’) (h:m [SD]), from the symptoms onset to admission in emergency unit was 02:29’(02:00’) and from admission in emergency unit to administration of thrombolytic drug was 01:04’(01:14’).
CONCLUSIONS:
Time interval between onset of the acute coronary symptoms and seek for medical care and arrival to the emergency unit in this study had a better condition than other studies, but the interval between the emergency admission and thrombolytic therapy was longer than other studies.
PMCID: PMC3208947  PMID: 22069414
Acute coronary syndrome; acute myocardial infarction; thrombolytic therapy
5.  Predictors of contractile recovery after revascularization in patients with anterior myocardial infarction who received thrombolysis 
BACKGROUND:
Identification of viable myocardium after myocardial infarction has gained paramount importance with the current progress in coronary revascularization.
OBJECTIVE:
To explore the prognostic power of certain patient characteristics to predict myocardial contractile recovery after revascularization in patients presenting with acute anterior ST elevation myocardial infarction (STEMI) who received thrombolytic therapy.
METHODS:
Seventy-three consecutive patients presenting with first acute anterior STEMI who had received thrombolytic therapy and had significant coronary stenosis or occlusion of the infarct-related artery amenable for revascularization were enrolled. All patients underwent echocardiographic assessment of regional wall motion and left ventricular ejection fraction. Patients underwent coronary revascularization by either percutaneous angioplasty or surgical bypass. Echocardiography was repeated two to three months following revascularization. Patients were classified into two groups: group 1 had evidence of contractile recovery after revascularization at follow-up echocardiography and group 2 had no such evidence of recovery.
RESULTS:
Predictors of contractile recovery after revascularization included a shorter time from symptom onset to the institution of thrombolytic therapy, a lower baseline wall motion score index, the presence of grade 3 collaterals to the infarct-related artery and the use of beta-blockers. Instead, the presence of diabetes mellitus and a totally occluded infarct-related artery predicted poor contractile recovery.
CONCLUSIONS:
Myocardial contractile recovery after revascularization in patients presenting with first acute anterior STEMI may be predicted by the absence of diabetes, a shorter time from symptom onset to thrombolytic therapy, the use of beta-blockers, a lower initial wall motion index score and the presence of collaterals to the infarct-related artery.
PMCID: PMC3005410  PMID: 22477594
Myocardial infarction; Predictors; Revascularization; Viability
6.  Cardiovascular magnetic resonance of scar and ischemia burden early after acute ST elevation and non-ST elevation myocardial infarction 
Background
The acute coronary syndrome diagnosis includes different classifications of myocardial infarction, which have been shown to differ in their pathology, as well as their early and late prognosis. These differences may relate to the underlying extent of infarction and/or residual myocardial ischemia. The study aim was to compare scar and ischemia mass between acute non-ST elevation myocardial infarction (NSTEMI), ST-elevation MI with Q-wave formation (Q-STEMI) and ST-elevation MI without Q-wave formation (Non-Q STEMI) in-vivo, using cardiovascular magnetic resonance (CMR).
Methods and results
This was a prospective cohort study of twenty five consecutive patients with NSTEMI, 25 patients with thrombolysed Q-STEMI and 25 patients with thrombolysed Non-Q STEMI. Myocardial function (cine imaging), ischemia (adenosine stress first pass myocardial perfusion) and scar (late gadolinium enhancement) were assessed by CMR 2–6 days after presentation and before any invasive revascularisation procedure. All subjects gave written informed consent and ethical committee approval was obtained. Scar mass was highest in Q-STEMI, followed by Non-Q STEMI and NSTEMI (24.1%, 15.2% and 3.8% of LV mass, respectively; p < 0.0001). Ischemia mass showed the reverse trend and was lowest in Q-STEMI, followed by Non-Q STEMI and NSTEMI (6.9%, 14.7% and 19.9% of LV mass, respectively; p = 0.012). The combined mass of scar and ischemia was similar between the three groups (p = 0.17). The ratio of scar to ischemia was 3.5, 1.0 and 0.2 for Q-STEMI, Non-Q STEMI and NSTEMI, respectively.
Conclusion
Prior to revascularisation, the ratio of scar to ischemia differs between NSTEMI, Non-Q STEMI and Q-STEMI, whilst the combined scar and ischemia mass is similar between these three types of MI. These results provide in-vivo confirmation of the diverse pathophysiology of different types of acute myocardial infarction and may explain their divergent early and late prognosis.
doi:10.1186/1532-429X-10-47
PMCID: PMC2584062  PMID: 18950527
7.  Effect of Thrombolytic Therapy on the Incidence of Early Left Ventricular Infarct Expansion in Acute Anterior Myocardial Infarction 
Oman Medical Journal  2011;26(6):431-435.
Objectives
To determine the incidence of early left ventricular infarct expansion within five days after first anterior ST-segment elevation myocardial infarction and the effect of early thrombolytic therapy on the incidence of early infarct expansion compared with late thrombolytic therapy.
Methods
In a prospective study of 101 patients (75males and 26 females), with the first attack of acute anterior myocardial infarction, their ages ranged from 40-80 years (mean age: 61.07±10.78) who had been admitted to the Coronary Care Unit of Hawler Teaching Hospital for the period from July 2007 through to September 2009. Those who received alteplase ≤3 hours of acute myocardial infarction were labelled as group-I (49 patients) and those who received alteplase >3-12 hours were labelled as group-II (52 patients).
Results
The incidence of early left ventricular infarct expansion was diagnosed by 2D-echocardiography and was found to be 17.8%. Group I patients had a lower incidence of early left ventricular infarct expansion (8.16%) compared with group-II (26.92%; p=0.014). Patients with early left ventricular infarct expansion had a higher frequency rate of left ventricular systolic dysfunction (94.44%) compared to patients without early left ventricular infarct expansion (8.43%; p<0.001). There was a significant difference in the incidence of in-hospital mortality between the patients who developed early left ventricular infarct expansion (11.1%) compared with patients without early left ventricular infarct expansion (1.2%; p=0.025).
Conclusion
Early reperfusion therapy in acute anterior myocardial infarction can decrease the incidence of early left ventricular infarct expansion, preserve left ventricular systolic function and decrease in-hospital mortality.
doi:10.5001/omj.2011.109
PMCID: PMC3251193  PMID: 22253953
Left ventricular infarct expansion; Alteplase
8.  Are patients with non-ST elevation myocardial infarction undertreated? 
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.
doi:10.1186/1471-2261-7-8
PMCID: PMC1832214  PMID: 17338808
9.  Transfer for urgent percutaneous coronary intervention early after thrombolysis for ST-elevation myocardial infarction: The TRANSFER-AMI pilot feasibility study 
The Canadian Journal of Cardiology  2006;22(13):1121-1126.
BACKGROUND
Most hospitals in Canada do not have percutaneous coronary intervention (PCI) facilities and use thrombolysis as reperfusion therapy for ST-elevation myocardial infarction (STEMI). Urgent PCI after thrombolysis may optimize reperfusion and prevent reinfarction and recurrent ischemia.
OBJECTIVE
To determine the feasibility of transferring high-risk STEMI patients from community hospitals in Ontario to PCI centres for urgent PCI within 6 h of thrombolysis.
METHODS
Patients with anterior or high-risk inferior STEMI received tenecteplase and were urgently transferred to PCI centres. PCI was performed if at least 70% stenosis was present in the infarct-related artery, regardless of flow, using coronary stents. Transfer of stable patients back to community hospitals was encouraged 24 h to 48 h after PCI.
RESULTS
Eighteen patients were transferred and underwent PCI a median of 3.9 h (range 2.7 h to 6.4 h) after thrombolysis. No complications occurred during transfer. One death occurred that was related to failed reperfusion and cardiogenic shock. Minor access-site bleeding occurred in five patients. Fifteen patients were transferred back to their community hospitals within 24 h of PCI. There were no further deaths or reinfarctions at one-year follow-up.
CONCLUSIONS
Transfer of high-risk STEMI patients for urgent PCI within 6 h after thrombolysis appears feasible. The randomized trial phase of the Trial of Routine ANgioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI) will compare this strategy with standard treatment after thrombolysis.
PMCID: PMC2569051  PMID: 17102829
Angioplasty; Clinical trials; Myocardial infarction; Thrombolysis
10.  Acute myocardial infarction system of care in the third world 
Netherlands Heart Journal  2012;20(6):254-259.
Background
We studied the characteristics of ST-elevation myocardial infarction (STEMI) patients from a local acute coronary syndrome (ACS) registry in order to find and build an appropriate acute myocardial infarction (AMI) system of care in Jakarta, Indonesia.
Methods
Data were collected from the Jakarta Acute Coronary Syndrome (JAC) registry 2008–2009, which contained 2103 ACS patients, including 654 acute STEMI patients admitted to the National Cardiovascular Center Harapan Kita, Jakarta, Indonesia.
Results
The proportion of patients who did not receive reperfusion therapy was 59% in all STEMI patients and the majority of them (52%) came from inter-hospital referral. The time from onset of infarction to hospital admission was more than 12 h in almost 80% cases and 60% had an anterior wall MI. In-hospital mortality was significantly higher in patients who did not receive reperfusion therapy compared with patients receiving acute reperfusion therapy, either with primary percutaneous coronary intervention (PPCI) or fibrinolytic therapy (13.3% vs 5.3% vs 6.2%, p < 0.001).
Conclusion
The Jakarta Cardiovascular Care Unit Network System was built to improve the care of AMI in Jakarta. This network will harmonise the activities of all hospitals in Jakarta and will provide the best cardiovascular services to the community by giving two reperfusion therapy options (PPCI or pharmaco-invasive strategy) depending on the time needed for the patient to reach the cath-lab.
doi:10.1007/s12471-012-0259-9
PMCID: PMC3370084  PMID: 22328356
ST-elevation myocardial infarction; System of care; Pharmaco-invasive strategy
11.  Efficacy and Safety of Low-Molecular-Weight Heparins As An Adjunct to Thrombolysis in Acute ST-Elevation Myocardial Infarction 
Current Cardiology Reviews  2008;4(1):63-71.
A 48-hour course of intravenous unfractionated heparin (UFH) is the standard of treatment in conjunction with fibrin-specific thrombolysis in ST-elevation myocardial infarction (STEMI). In recent trials, the efficacy and safety of in-hospital administration of subcutaneous low-molecular-weight heparins (LMWH), previously proven effective in non-ST-elevation acute coronary syndromes, have been investigated in the setting of STEMI. The aim of this review was to evaluate the available evidence supporting the use of LMWH in STEMI.
Overall, about 27,000 patients treated with various thrombolytic regimens, were included in 12 open-label randomized clinical trials, where dalteparin, reviparin or enoxaparin were administered. While acknowledging the wide variability in study dimensions, designs and end-points, a higher efficacy of LMWH was observed overall as compared to placebo, and also to UFH (mainly as regards the occurrence of reinfarction). As regards safety, bleedings were more frequent than placebo and comparable to UFH in LMWH groups, with the exception of the pre-hospital ASSENT-3 PLUS trial, where in elderly patients, enoxaparin had an incidence of intracranial hemorrhage twice higher than UFH. In a recent double-blind, randomized, mega-trial including over 20,000 patients, the superior efficacy on in-hospital and 30-day adverse cardiac events (namely reinfarction), and comparable safety on intracranial bleedings, of enoxaparin compared to UFH, was shown.
In conclusion, in-hospital subcutaneous administration of dalteparin, reviparin and enoxaparin, as an adjunct to various thrombolytics in STEMI, appears feasible and at least as effective and safe as 48-hour intravenous treatment with UFH. In accordance with the available strongest evidence, an initial intravenous bolus of enoxaparin followed by twice daily subcutaneous administration for about 1 week should be the preferred regimen, and should be strongly considered instead of intravenous UFH. Along with its easiness of use, not requiring laboratory monitoring, subcutaneous administration of LMWH following STEMI treated with thrombolysis allows extended antithrombotic treatment, while permitting early mobilization (and rehabilitation) of patients.
doi:10.2174/157340308783565438
PMCID: PMC2774587  PMID: 19924279
ST-elevation acute myocardial infarction; enoxaparin; dalteparin; reviparin; unfractionated heparin.
12.  Pharmacological and Non-Pharmacological Recanalization Strategies in Acute Ischemic Stroke 
According to the guidelines of the European Stroke Organization (ESO) and the American Stroke Association (ASA), acute stroke patients should be managed at stroke units that include well organized pre- and in-hospital care. In ischemic stroke the restoration of blood flow has to occur within a limited time window that is accomplished by fibrinolytic therapy. Newer generation thrombolytic agents (alteplase, pro-urokinase, reteplase, tenecteplase, desmoteplase) have shorter half-life and are more fibrin-specific. Only alteplase has Food and Drug Administration (FDA) approval for the treatment of acute stroke (1996). The National Institute of Neurological Disorders and Stroke (NINDS) trial proved that alteplase was effective in all subtypes of ischemic strokes within the first 3 h. In the European cooperative acute stroke study III trial, intravenous (IV) alteplase therapy was found to be safe and effective (with some restrictions) if applied within the first 3–4.5 h. In middle cerebral artery (MCA) occlusion additional transcranial Doppler insonication may improve the breakdown of the blood clot. According to the ESO and ASA guidelines, intra-arterial (IA) thrombolysis is an option for recanalization within 6 h of MCA occlusion. Further trials on the IA therapy are needed, as previous studies have involved relatively small number of patients (compared to IV trials) and the optimal IA dose of alteplase has not been determined (20–30 mg is used most commonly in 2 h). Patients undergoing combined (IV + IA) thrombolysis had significantly better outcome than the placebo group or the IV therapy alone in the NINDS trial (Interventional Management of Stroke trials). If thrombolysis fails or it is contraindicated, mechanical devices [e.g., mechanical embolus removal in cerebral ischemia (MERCI)- approved in 2004] might be used to remove the occluding clot. Stenting can also be an option in case of acute internal carotid artery occlusion in the future. An intra-aortic balloon was used to increase the collateral blood flow in the Safety and Efficacy of NeuroFlo™ Technology in Ischemic Stroke trial (results are under evaluation). Currently, there is no approved effective neuroprotective drug.
doi:10.3389/fneur.2011.00032
PMCID: PMC3105226  PMID: 21660098
intravenous thrombolysis; intra-arterial thrombolysis; acute stroke; mechanism of recanalization; thrombectomy; alteplase; stroke unit; therapeutic time window
13.  Cardiac Function, Perfusion, Metabolism, and Innervation following Autologous Stem Cell Therapy for Acute ST-Elevation Myocardial Infarction. A FINCELL-INSIGHT Sub-Study with PET and MRI 
Purpose: Beneficial mechanisms of bone marrow cell (BMC) therapy for acute ST-segment elevation myocardial infarct (STEMI) are largely unknown in humans. Therefore, we evaluated the feasibility of serial positron emission tomography (PET) and MRI studies to provide insight into the effects of BMCs on the healing process of ischemic myocardial damage. Methods: Nineteen patients with successful primary reteplase thrombolysis (mean 2.4 h after symptoms) for STEMI were randomized for BMC therapy (2.9 × 106 CD34+ cells) or placebo after bone marrow aspiration in a double-blind, multi-center study. Three days post-MI, coronary angioplasty, and paclitaxel eluting stent implantation preceded either BMC or placebo therapy. Cardiac PET and MRI studies were performed 7–12 days after therapies and repeated after 6 months, and images were analyzed at a central core laboratory. Results: In BMC-treated patients, there was a decrease in [11C]-HED defect size (−4.9 ± 4.0 vs. −1.6 ± 2.2%, p = 0.08) and an increase in [18F]-FDG uptake in the infarct area at risk (0.06 ± 0.09 vs. −0.05 ± 0.16, p = 0.07) compared to controls, as well as less left ventricular dilatation (−4.4 ± 13.3 vs. 8.0 ± 16.7 mL/m2, p = 0.12) at 6 months follow-up. However, BMC treatment was inferior to placebo in terms of changes in rest perfusion in the area at risk (−0.09 ± 0.17 vs. 0.10 ± 0.17, p = 0.03) and infarct size (0.4 ± 4.2 vs. −5.1 ± 5.9 g, p = 0.047), and no effect was observed on ejection fraction (p = 0.37). Conclusion: After the acute phase of STEMI, BMC therapy showed only minor trends of long-term benefit in patients with rapid successful thrombolysis. There was a trend of more decrease in innervation defect size and enhanced glucose metabolism in the infarct-related myocardium and also a trend of less ventricular dilatation in the BMC-treated group compared to placebo. However, no consistently better outcome was observed in the BMC-treated group compared to placebo.
doi:10.3389/fphys.2012.00006
PMCID: PMC3277266  PMID: 22363288
stem cell therapy; myocardial infarct; PET; MRI
14.  Validation of the Thrombolysis in Myocardial Infarction (TIMI) risk index for predicting early mortality in a population-based cohort of STEMI and non-STEMI patients 
BACKGROUND:
The Thrombolysis In Myocardial Infarction (TIMI) risk index for the prediction of 30-day mortality was developed and validated in patients with ST-segment elevation myocardial infarction (STEMI) who were being treated with thrombolytics in randomized clinical trials. When tested in clinical registries of patients with STEMI, the index performed poorly in an older (65 years and older) Medicare population, but it was a good predictor of early death among the more representative population on the National Registry of Myocardial Infarction-3 and -4 databases. It has not been tested in a population outside the United States or among non-STEMI patients.
METHODS:
The TIMI risk index was applied to the Enhanced Feedback for Effective Cardiac Treatment (EFFECT) study cohort of 11,510 acute MI patients from Ontario. The model’s discriminatory capacity and calibration were tested in all patients and in subgroups determined by age, sex, diagnosis and reperfusion status.
RESULTS:
The TIMI risk index was strongly associated with 30-day mortality for both STEMI and non-STEMI patients. The C statistic was 0.82 for STEMI and 0.80 for non-STEMI patients, with overlapping 95% CI. The discriminatory capacity was somewhat lower for patients older than 65 years of age (0.74). The model was well calibrated.
CONCLUSIONS:
The TIMI risk index is a simple, valid and moderately accurate tool for the stratification of risk for early death in STEMI and non-STEMI patients in the community setting. Its routine clinical use is warranted.
PMCID: PMC2649172  PMID: 17245483
Coronary disease; Myocardial infarction; Risk factors
15.  Management and in-hospital outcome of patients with acute myocardial infarction admitted to intensive care units at the turn of the century: results from the French nationwide USIC 2000 registry 
Heart  2004;90(12):1404-1410.
Objective: To assess actual practices and in-hospital outcome of patients with acute myocardial infarction on a nationwide scale.
Methods: Of 443 intensive care units in France, 369 (83%) prospectively collected data on all cases of infarction (within < 48 hours of symptom onset) in November 2000.
Results: 2320 patients (median age 68 years, 73% men) were included, of whom 83% had ST segment elevation infarction (STEMI). Patients without STEMI were older and had a more frequent history of cardiovascular disease. Median time to admission was 5.0 hours for patients with and 6.5 hours for those without STEMI. Reperfusion therapy was used for 53% of patients with STEMI (thrombolysis 28%, primary angioplasty 25%). In-hospital mortality was 8.7% (5.5% of patients without and 9.3% of those with STEMI). Multivariate analysis found that age, Killip class, lower blood pressure, higher heart rate on admission, anterior location of infarct, STEMI, diabetes mellitus, previous stroke, and no current smoking independently predicted in-hospital mortality. At hospital discharge, 95% received antiplatelet agents, 75% received β blockers, and over 60% received statins. Angiotensin converting enzyme inhibitors were prescribed for 40% of the patients without and 52% of those with ST elevation.
Conclusions: This nationwide registry, including all types of centres irrespective of their size and experience, shows continued improvement in patient care and outcomes. Time from symptom onset to admission, however, has not improved in recent years and reperfusion therapy is used for just over 50% of patients with STEMI, with an increasing use of primary angioplasty.
doi:10.1136/hrt.2003.025460
PMCID: PMC1768566  PMID: 15547013
myocardial infarction; intensive care units; in-hospital outcome
16.  Random Treatment Assignment Using Mathematical Equipoise for Comparative Effectiveness Trials 
In controlled clinical trials, random assignment of treatment is appropriate only when there is equipoise, i.e., no clear preference among treatment options. However, even when equipoise appears absent because prior trials show, on average, one treatment yields superior outcomes, random assignment still may be appropriate for some patients and circumstances. In such cases, enrollment into trials may be assisted by real-time patient-specific predictions of treatment outcomes, to determine whether there is equipoise to justify randomization.
The Percutaneous Coronary Intervention Thrombolytic Predictive Instrument (PCI-TPI) computes probabilities of 30-day mortality for patients having ST elevation myocardial infarction (STEMI), if treated with thrombolytic therapy, and if treated with PCI. We estimated uncertainty around differences in their respective predicted benefits using the estimated uncertainty of the model coefficients. Using the 2,781-patient PCI-TPI development dataset, we evaluated the distribution of predicted benefits for each patient. For three typical clinical situations, randomization was potentially warranted for 70%, 93%, and 80% of patients.
Predictive models may allow real-time patient-specific determination of whether there is equipoise that justifies trial enrollment for a given patient. This approach may have utility for comparative effectiveness trials and for application of trial results to clinical practice.
doi:10.1111/j.1752-8062.2010.00253.x
PMCID: PMC3076795  PMID: 21348950
17.  Regionalization of ST-Segment Elevation Acute Coronary Syndromes Care Putting a National Policy in Proper Perspective 
A uniform policy for regionalization of ST-segment elevation myocardial infarction (STEMI) care raises several concerns. Transferring all STEMI patients to obtain primary percutaneous coronary intervention (PCI) may be less effective than transferring only high-risk STEMI patients. Delays in time to treatment >60 min associated with transferring patients for primary PCI may result in increased mortality for the average patient as compared with providing immediate fibrinolytic therapy at their initial hospital; yet more than 95% of patients transferred for primary PCI in the U.S. exceed this 60-min benchmark. Superior outcomes associated with treatment at higher-volume regional STEMI centers are inconsistent among centers, and there is no direct evidence that patients will benefit by a transfer to a high-volume hospital from a low-volume hospital. Published data suggest as many as 800 PCI patients would need to be transferred to a high-volume PCI hospital to avoid a single death at a low-volume PCI hospital. Although European randomized trial data suggest transferring patients with STEMI for primary PCI may be superior to immediate fibrinolytic therapy, these findings are unlikely to generalize to the U.S. health care system given size, geography, and organization. ST segment elevation myocardial infarction care regionalization would require a massive redistribution of health care resources, depriving several hospitals of advanced cardiac care facilities, expertise, and associated revenue. Clearer evidence of the benefits and discussion of potential harms are needed before adopting a national STEMI regionalization policy.
doi:10.1016/j.jacc.2005.11.053
PMCID: PMC2789345  PMID: 16580519
18.  Thrombolytic Therapy for Acute Coronary Obstruction: Status in 1986 
Texas Heart Institute Journal  1986;13(4):433-445.
The effect of thrombolysis in acute myocardial infarction on enzymatic infarct size, left ventricular function, and early mortality was studied in subsets of patients in a randomized trial at The Netherlands Interuniversity Cardiological Institute during a 5-year period. Early thrombolytic therapy with intracoronary streptokinase (152 patients) or with intracoronary streptokinase preceded by intravenous streptokinase (117 patients) was compared to conventional treatment (264 patients). All 533 patients were admitted to the coronary care unit within 4 hours after onset of symptoms indicative of acute myocardial infarction. There were 488 patients eligible for this detailed analysis, of whom 245 were allocated for thrombolytic therapy. Early angiography was performed in 212 of the 245 patients. Patency of the infarct-related artery was achieved in 181 patients (85%). Enzymatic infarct size measured from cumulative alpha HBDH release was smaller in patients allocated to thrombolytic therapy (median 760 U/l vs. 1179 U/l in controls, p = 0.0001). LVEF measured by radionuclide angiography before discharge was higher after thrombolytic therapy (median 50% vs. 43% in controls, p = 0.0001). The 12-month mortality was lower in patients allocated to thrombolytic therapy (8% vs. 16% in the control group, p < 0.01). In multivariate regression analysis, infarct size limitation, improvement of LVEF, and a 3-month mortality were predicted by ST, time from onset of symptoms to admission, and Killip class at admission. Thrombolysis was most useful in patients admitted within 2 hours after onset of symptoms and in patients with ST of 1.2 mV or more. On the other hand, no beneficial effects of streptokinase on enzymatic infarct size, left ventricular function, or mortality were observed in the subset of patients with ST less than 1.2 mV admitted 2 to 4 hours after onset of symptoms.
In the long term, improved survival and enhanced quality of life are most evident after thrombolytic therapy in patients with larger anterior wall infarction, and less pronounced in patients with smaller inferior wall infarction. (Texas Heart Institute Journal 1986; 13:433-445)
Images
PMCID: PMC324674  PMID: 15227352
Thrombolysis; streptokinase therapy; myocardial infarction
19.  Significance of initial ST segment changes for thrombolytic treatment in first inferior myocardial infarction. 
Heart  1997;77(6):506-511.
OBJECTIVE: To evaluate the benefit to risk ratio of thrombolytic treatment in patients with small inferior acute myocardial infarction (AMI). Controlled studies relating the benefit from thrombolysis with initial electrocardiographic features are scarce and of limited sample size. DESIGN: Retrospective study of 728 patients with a first inferior AMI of six hours' duration from the Intravenous Streptokinase in Acute Myocardial Infarction (ISAM) study comparing streptokinase with placebo stratified by the initial sum ST segment elevation (sigma ST) of 0.8 mV or less and greater than 0.8 mV, and 636 patients from the International Joint Efficacy Comparison of Thrombolytics (INJECT) trial comparing double blind streptokinase with reteplase stratified by either sigma ST or the presence of precordial ST segment depression. RESULTS: ISAM study patients with an sigma ST of greater than 0.8 mV had a significant mortality benefit from streptokinase throughout six years, while those with an sigma ST of 0.8 mV or less showed a trend to higher mortality at six months (6.3% streptokinase v 5.1% placebo). Despite significantly smaller infarcts and fewer clinical complications in patients with an sigma ST of 0.8 mV or less (ISAM and INJECT) or the absence of precordial ST segment depression (INJECT) thrombolytic treatment was associated with higher early mortality than in those with initially larger ST segment deviations. CONCLUSION: Thrombolytic treatment in patients with inferior AMI presenting with larger ST segment deviations is associated with improved survival throughout six years. The risk to benefit ratio, however, in terms of early mortality in patients who have an sigma ST of 0.8 mV or less and no precordial ST segment depression may be unfavourable.
PMCID: PMC484791  PMID: 9227292
20.  Rescue thrombolysis: alteplase as adjuvant treatment after streptokinase in acute myocardial infarction. 
British Heart Journal  1995;74(4):348-353.
BACKGROUND--In acute myocardial infarction patients who do not reperfuse their infarct arteries shortly after thrombolytic treatment have a high morbidity and mortality. Management of this high risk group remains problematic, especially in centres without access to interventional cardiology. Additional thrombolytic treatment may result in reperfusion and improved left ventricular function. METHODS--Failure of reperfusion was assessed non-invasively as less than 25% reduction of ST elevation in the electrocardiographic lead with maximum ST shift on a pretreatment electrocardiogram. 37 patients with acute myocardial infarction who showed electrocardiographic evidence of failed reperfusion 30 minutes after 1.5 MU streptokinase over 60 minutes were randomly allocated to receive either alteplase (tissue type plasminogen activator (rt-PA) 100 mg over three hours) (19 patients) or placebo (18 patients). 43 patients with electrocardiographic evidence of reperfusion after streptokinase acted as controls. Outcome was assessed from the Selvester Q wave score of a predischarge electrocardiogram and a nuclear gated scan for left ventricular ejection fraction 4-6 weeks after discharge. RESULTS--Among patients in whom ST segment elevation was not reduced after streptokinase, alteplase treatment resulted in a significantly smaller electrocardiographic infarct size (14% (8%) v 20% (9%), P = 0.03) and improved left ventricular ejection fraction (44 (10%) v 34% (16%), P = 0.04) compared with placebo. This benefit was confined to patients who failed fibrinogenolysis after streptokinase (fibrinogen > 1 g/l). In patients in whom ST segment elevation was reduced after streptokinase, infarct size and left ventricular ejection fraction were not significantly different from those in patients treated with additional alteplase. CONCLUSION--Patients without electrocardiographic evidence of reperfusion after streptokinase may benefit from further thrombolysis with alteplase.
PMCID: PMC484036  PMID: 7488444
21.  Peripheral Arterial Disease in Patients Presenting with Acute Coronary Syndrome in Six Middle Eastern Countries 
To describe prevalence and impact of peripheral arterial disease (PAD) in patients with acute coronary syndrome (ACS), data were collected over 5 months from 6 Middle Eastern countries. Patients were divided into 2 groups (with and without PAD). Out of 6705 consecutive ACS patients, PAD was reported in 177 patients. In comparison to non-PAD, PAD patients were older and more likely to have cardiovascular risk factors. They were more likely to have high Killip class, high GRACE risk score, and non-ST elevation ACS (NSTEACS) at presentation. Thrombolytics, antiplatelet use, and coronary intervention were comparable in both groups. When presented with ST-elevation myocardial infarction (STEMI), patients with PAD had worse outcomes, while in NSTEACS; PAD was associated with higher rate of heart failure in comparison to non-PAD patients. In diabetics, PAD was associated with 2-fold increase in mortality when compared to non-PAD (P = 0.028). After adjustment, PAD was associated with high mortality in STEMI (adjusted OR 2.6; 95% CI 1.23–5.65, P = 0.01). Prevalence of PAD in ACS in the Gulf region is low. Patients with PAD and ACS constitute a high risk group and require more attention. PAD in patients with STEMI is an independent predictor of in-hospital death.
doi:10.1155/2011/815902
PMCID: PMC3246760  PMID: 22220279
22.  Clinical implications of ST-segment non-resolution after thrombolysis for myocardial infarction 
Failed reperfusion after thrombolytic therapy for acute myocardial infarction is common and signifies a poor prognosis. We investigated the clinical consequences of non-resolution of the ST segment after thrombolytic therapy for acute ST-elevation myocardial infarction, in 85 consecutive patients admitted to a coronary care unit lacking rapid access to angioplasty. Failed thrombolysis was defined as <50% ST-segment resolution 180 minutes after the start of thrombolytic treatment. Outcomes were measured in terms of in-hospital adverse events, length of hospital stay, and mortality at 6 weeks and 1 year.
Thrombolysis was successful, in terms of ST-segment resolution, in 45 patients (53%). After adjustment for other factors, ST resolution was the only independent predictor of an uncomplicated recovery in hospital (odds ratio 6.8, 95% confidence interval 2.3 to 19.9; P<0.001). At 6 weeks and 1 year, overall mortality was lower in the ST resolution group, though these differences became non-significant on multivariate analysis. In patients who survived to hospital discharge, median length of stay was greater in successfully thrombolysed patients (9 days versus 8 days) despite their lower rate of complications.
ST-segment resolution is a useful marker of successful thrombolysis and relates to clinical outcome. If assessed routinely it might assist, along with other clinical markers, in the identification of low-risk patients who can be discharged early.
PMCID: PMC1079667  PMID: 15574852
23.  Immunoglobulin response to intravenous streptokinase in acute myocardial infarction. 
British Heart Journal  1991;66(2):139-142.
OBJECTIVE--To devise assays to assess and follow the specific antibody response in patients treated with streptokinase for acute myocardial infarction. DESIGN--Venous blood samples were collected before treatment with streptokinase started and subsequently at regular intervals over one year. Specific IgG and subclass IgG1 were assessed by an enzyme linked immunosorbent assay. SETTING--Coronary care unit in a general hospital. PATIENTS--48 patients with acute myocardial infarction: 22 patients had venous blood samples taken at presentation only; serial blood samples were taken from 20 patients who then received thrombolytic therapy with streptokinase and six patients who were unsuitable for thrombolytic therapy. RESULTS--Titres of antibodies to streptokinase were low at presentation in 36 (75%) of the 48 patients. Serial measurements made in 20 patients showed the virtual disappearance of antibody within the first 24 hours. This was followed by a steady increase in the specific IgG1 titre, which peaked at day 14 before gradually declining. Values at one year remained significantly higher than baseline values. There was no evidence of an IgM response in the patients studied. CONCLUSION--Low titres of antibodies to streptokinase were widespread in the population. Antibody was consumed after treatment and the subsequent immunoglobulin rise suggested a secondary immune responses; the recently described neutralising capacity to streptokinase is probably related to this antibody.
PMCID: PMC1024604  PMID: 1883664
24.  An artificial neural network to safely reduce the number of ambulance ECGs transmitted for physician assessment in a system with prehospital detection of ST elevation myocardial infarction 
Background
Pre-hospital electrocardiogram (ECG) transmission to an expert for interpretation and triage reduces time to acute percutaneous coronary intervention (PCI) in patients with ST elevation Myocardial Infarction (STEMI). In order to detect all STEMI patients, the ECG should be transmitted in all cases of suspected acute cardiac ischemia. The aim of this study was to examine the ability of an artificial neural network (ANN) to safely reduce the number of ECGs transmitted by identifying patients without STEMI and patients not needing acute PCI.
Methods
Five hundred and sixty ambulance ECGs transmitted to the coronary care unit (CCU) in routine care were prospectively collected. The ECG interpretation by the ANN was compared with the diagnosis (STEMI or not) and the need for an acute PCI (or not) as determined from the Swedish coronary angiography and angioplasty register. The CCU physician's real time ECG interpretation (STEMI or not) and triage decision (acute PCI or not) were registered for comparison.
Results
The ANN sensitivity, specificity, positive and negative predictive values for STEMI was 95%, 68%, 18% and 99%, respectively, and for a need of acute PCI it was 97%, 68%, 17% and 100%. The area under the ANN's receiver operating characteristics curve for STEMI detection was 0.93 (95% CI 0.89-0.96) and for predicting the need of acute PCI 0.94 (95% CI 0.90-0.97). If ECGs where the ANN did not identify a STEMI or a need of acute PCI were theoretically to be withheld from transmission, the number of ECGs sent to the CCU could have been reduced by 64% without missing any case with STEMI or a need of immediate PCI.
Conclusions
Our ANN had an excellent ability to predict STEMI and the need of acute PCI in ambulance ECGs, and has a potential to safely reduce the number of ECG transmitted to the CCU by almost two thirds.
doi:10.1186/1757-7241-20-8
PMCID: PMC3293011  PMID: 22296816
25.  Medical audit and formulary management: a policy for rational use of thrombolytic drugs. 
Postgraduate Medical Journal  1991;67(784):165-169.
In this article we report on the development, introduction, and maintenance of a policy to promote rational use of thrombolytic drugs by hospital doctors. The work was undertaken within the framework of the voluntarily operated Riverside East drugs guide (formulary) management system (FMS). The policy was introduced in October 1988 and revised in November 1989 to coincide with the launch of the new, expensive thrombolytic drugs, alteplase (rt-PA, Actilyse) in 1988 and antistreplase (APSAC, Eminase) in 1989. Streptokinase was recommended as the first-line drug for patients who had not received it within the last 6 months. The policy was communicated to all staff in meetings and a drugs guide bulletin and reinforced by ward pharmacists. Results over a 15 month period show voluntary compliance by prescribers with the recommended policy. One hundred and seventy-four patients (22% cardiac admissions) presented with acute myocardial infarction. Of these 43 (25%) received streptokinase, the first-line recommended drug, 7 received alteplase and none received anistreplase. The savings in drug expenditure from using streptokinase rather than alteplase or anistreplase for the 15-month period of investigation were over pounds 27,000. This work represents an example of the effectiveness of the Riverside East FMS model in influencing prescribing behaviour.
PMCID: PMC2398965  PMID: 1904156

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