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.
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.
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.
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.
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.
diabetes mellitus; acute myocardial infarction; angioplasty; clinical outcome; ventricular function
Traditionally, acute myocardial infarction (AMI) has been described as either STEMI (ST-elevation myocardial infarction) or non-STEMI myocardial infarction. This classification is historically related to the use of thrombolytic therapy, which is effective in STEMI. The current era of widespread use of coronary angiography (CAG), usually followed by primary percutaneous coronary intervention (PCI) puts this classification system into question.
To compare the outcomes of patients with STEMI and ST-depression myocardial infarction (STDMI) who were treated with emergency PCI.
This multicentre registry enrolled a total of 6 602 consecutive patients with AMI. Patients were divided into the following subgroups: STEMI (n = 3446), STDMI (n = 907), left bundle branch block (LBBB) AMI (n = 241), right bundle branch block (RBBB) AMI (n = 338) and other electrocardiographic (ECG) AMI (n = 1670). Baseline and angiographic characteristics were studied, and revascularisation therapies and in-hospital mortality were analysed.
Acute heart failure was present in 29.5% of the STDMI vs 27.4% of the STEMI patients (p < 0.001). STDMI patients had more extensive coronary atherosclerosis than patients with STEMI (three-vessel disease: 53.1 vs 30%, p < 0.001). The left main coronary artery was an infract-related artery (IRA) in 6.0% of STDMI vs 1.1% of STEMI patients (p < 0.001). TIMI flow 0–1 was found in 35.0% of STDMI vs 66.0% of STEMI patients (p < 0.001). Primary PCI was performed in 88.1% of STEMI (with a success rate of 90.8%) vs 61.8% of STDMI patients (with a success rate of 94.5%) (p = 0.012 for PCI success rates). In-hospital mortality was not significantly different (STDMI 6.3 vs STEMI 5.4%, p = 0.330).
These data suggest that similar strategies (emergency CAG with PCI whenever feasible) should be applied to both these types of AMI.
coronary artery disease; acute myocardial infarction; primary PCI
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.
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.
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.
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.
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’).
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.
Acute coronary syndrome; acute myocardial infarction; thrombolytic therapy
Identification of viable myocardium after myocardial infarction has gained paramount importance with the current progress in coronary revascularization.
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.
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.
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.
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.
Myocardial infarction; Predictors; Revascularization; Viability
Objective. Early restoration of coronary perfusion by thrombolysis or percutaneous coronary intervention is the main modality of treatment to salvage the ischemic myocardium. The earlier the procedure is completed, the greater the benefit is in saving myocardium and restoring its functions. The aim of the study is to compare the door-to-needle time (DNT) in acute ST elevation myocardial infarction (STEMI) in the period prior to December 2008 when the site of thrombolysis was in coronary care unit (CCU) and the period after that when the site was shifted to emergency department (ED). Methods. A retrospective, descriptive study was conducted at Al Khor Hospital, Qatar, in patients with acute STEMI who underwent thrombolysis at CCU and ED from April 2005 until December 2011, to compare the DNT, duration of hospitalization, and mortality. Results. A total of 211 patients with acute STEMI were eligible for thrombolysis; 58 patients were thrombolysed in the CCU and 153 in ED. The median DNT was reduced from 33.5 minutes in the CCU to 17 minutes in the ED representing a reduction of more than 50% with a P value of < 0.0001. Conclusion. The transfer of the thrombolysis site from CCU to the ED was associated with a dramatic and significant reduction in median door-to-needle time by more than half.
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.
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.
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.
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).
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).
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.
Left ventricular infarct expansion; Alteplase
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.
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.
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.
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.
Larger infarct size measured by creatine kinase (CK)-MB release is associated with higher mortality and has been used as an important surrogate endpoint in the evaluation of new treatments for ST-segment elevation myocardial infarction (STEMI). Traditional approaches to quantify infarct size include the observed CK-MB peak and calculated CK-MB area under the curve (AUC). We evaluated alternative approaches to quantifying infarct size using CK-MB values, and the relationship between infarct size and clinical outcomes.
Of 1,850 STEMI patients treated with reperfusion therapy in the COMplement inhibition in Myocardial infarction treated with Angioplasty (COMMA) (percutaneous coronary intervention (PCI)-treated) and the COMPlement inhibition in myocardial infarction treated with thromboLYtics (COMPLY) (fibrinolytic-treated) trials, 1,718 (92.9%) (COMMA, n = 868; COMPLY, n = 850) had at least five of nine protocol-required CK-MB measures. In addition to traditional methods, curve-fitting techniques were used to determine CK-MB AUC and estimated peak CK-MB. Cox proportional hazards modeling assessed the univariable associations between infarct size and mortality, and the composite of death, heart failure, shock and stroke at 90 days.
In COMPLY, CK-MB measures by all methods were significantly associated with higher mortality (hazard ratio range per 1,000 units increase: 1.09 to 1.13; hazard ratio range per 1 standard deviation increase: 1.41 to 1.62; P <0.01 for all analyses). In COMMA, the associations were similar but did not reach statistical significance. For the composite outcome of 90-day death, heart failure, shock and stroke, the associations with all CK-MB measures were statistically significant in both the COMMA and COMPLY trials.
Sophisticated curve modeling is an alternative to infarct-size quantification in STEMI patients, but it provides information similar to that of more traditional methods. Future studies will determine whether the same conclusion applies in circumstances other than STEMI, or to studies with different frequencies and patterns of CK-MB data collection.
Creatine kinase-MB; Infarct size; ST-segment elevation myocardial infarction; Clinical outcomes
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.
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.
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).
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.
ST-elevation myocardial infarction; System of care; Pharmaco-invasive strategy
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.
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.
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.
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.
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.
Angioplasty; Clinical trials; Myocardial infarction; Thrombolysis
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.
intravenous thrombolysis; intra-arterial thrombolysis; acute stroke; mechanism of recanalization; thrombectomy; alteplase; stroke unit; therapeutic time window
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.
ST-elevation acute myocardial infarction; enoxaparin; dalteparin; reviparin; unfractionated heparin.
Mortality from cardiovascular disease in the Middle East is projected to increase substantially in the coming decades. The prevalence of metabolic syndrome (MS) in acute coronary syndrome (ACS) continues to raise interest, but data from the Middle East is limited, especially in non-diabetic patients. This study was conducted to ascertain the prevalence of MS and frequency of its components, individually and in combination, in a male population presenting with ACS, but without a previous diagnosis of diabetes mellitus (DM).
This is a prospective study of 467 consecutive male patients hospitalized for ACS. They were categorized according to the specific criteria stated in the latest joint statement for the global definition of MS.
The mean age was (49.7±10.7 years). Of the 467 patients, 324 (69.4%) fulfilled the criteria for MS. ST-Elevation Myocardial Infarction (STEMI) was identified in 178 patients (54.9%), and non-ST elevation ACS (NSTE-ACS) in 146 patients (45.1%). These proportions were not significantly different from those without MS (STEMI 51.7% vs. NSTE-ACS 48.3%, respectively). However, patients with MS were older (50.6±10 vs. 47.9±11 years; p=0.012), and more than half of those with MS were above 50 years. The most common abnormal metabolic components were reduced high-density lipoprotein cholesterol (HDL-c; 94.1%), elevated fasting blood glucose (FBG; 89.8%), and elevated triglycerides (81.8%), followed by increased waist circumference (61.7%) and raised blood pressure (40.4%). The majority of patients with MS had three or more metabolic components (326 patients, 69.4%), and 102 (21.8%) had two components, but only 37 (8.4%) had a single component.
In ACS patients, without previous history of DM, MS is highly prevalent. Reduced HDL, elevated FBG and triglycerides were the most frequent metabolic components. The majority had multiple components. These findings raise alarm and show that drug therapy alone may not be fully effective, unless the underlying risk factors causing MS, such as weight and exercise, are also tackled.
male; metabolic syndrome; acute coronary syndrome; diabetes mellitus
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.
stem cell therapy; myocardial infarct; PET; MRI
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.
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.
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.
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.
Coronary disease; Myocardial infarction; Risk factors
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.
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)
Thrombolysis; streptokinase therapy; myocardial infarction
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.
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.
myocardial infarction; intensive care units; in-hospital outcome
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.
Over the past two decades, India has witnessed a staggering increase in the incidence and mortality of ST-elevation myocardial infarction (STEMI). Indians have higher rates of STEMI and younger populations that suffer from it when compared with developed countries. Yet, the recommended reperfusion therapy with fibrinolysis and percutaneous coronary intervention is available only to a minority of patients. This gap in care is a result of financial barriers, limited healthcare infrastructure and poor knowledge and accessibility of acute medical services for a majority of its population.
Methods and analysis
This is a prospective, multicentre, ‘pretest/post-test’ quasi-experimental, community-based study. This programme will use a ‘hub-and-spoke’ model of an integrated healthcare network based on clusters of primary-care health clinics, small hospitals and large tertiary-care facilities. It is an ‘all-comers’ study which will enrol consecutive patients presenting with STEMI to the participating hospitals. The primary objectives of the study is to improve the use of reperfusion therapy and reduce the time from first medical contact to device or drug in STEMI patients; and to increase the rates of early invasive risk stratification with coronary angiography within 3–24 h of fibrinolytic therapy in eligible patients through changes in process of care. Outcomes will be measured with statistical comparison made before and after implementing the TN-STEMI programme. The estimated sample size is based on the Kovai Erode Pilot study, which provided an initial work on establishing this type of programme in South India. It will be adequately powered at 80% with a superiority margin of 10% if 36 patients are enrolled per cluster or 108 patients in three clusters. Thus, the enrolment period of 9 months will result in a sample size of 1500 patients.
This study will be conducted in accordance with the ethical principles that have their origin in the current Declaration of Helsinki and ‘ethical guidelines for biomedical research on human participants’ as laid down by the Indian Council for Medical Research. All participating hospitals will still obtain local ethics committee approval of the study protocol and written informed consent will be obtained from all participants.
Dissemination and results
Our findings will be reported through scientific publications, research conferences and public policy venues aimed at state and local governments in India. If successful, this model can be extended to other areas of India as well as serve as a model of STEMI systems of care for low-income and middle-income countries across the world.
Trial is registered with Clinical trial registry of India, No: CTRI/2012/09/003002.
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.