Marko Noc

Reperfusion therapy for ST elevation acute myocardial infarction in Europe: description of the current situation in 30 countries

Aims Patient access to reperfusion therapy and the use of primary percutaneous coronary intervention (p-PCI) or thrombolysis (TL) varies considerably between European countries. The aim of this study was to obtain a realistic contemporary picture of how patients with ST elevation myocardial infarction (STEMI) are treated in different European countries. Methods and results The chairpersons of the national working groups/societies of interventional cardiology in European countries and selected experts known to be involved in the national registries joined the writing group upon invitation. Data were collected about the country and any existing national STEMI or PCI registries, about STEMI epidemiology, and treatment in each given country and about PCI and p-PCI centres and procedures in each country. Results from the national and/or regional registries in 30 countries were included in this analysis. The annual incidence of hospital admission for any acute myocardial infarction (AMI) varied between 90–312/100 thousand/year, the incidence of STEMI alone ranging from 44 to 142. Primary PCI was the dominant reperfusion strategy in 16 countries and TL in 8 countries. The use of a p-PCI strategy varied between 5 and 92% (of all STEMI patients) and the use of TL between 0 and 55%. Any reperfusion treatment (p-PCI or TL) was used in 37–93% of STEMI patients. Significantly less reperfusion therapy was used in those countries where TL was the dominant strategy. The number of p-PCI procedures per million per year varied among countries between 20 and 970. The mean population served by a single p-PCI centre varied between 0.3 and 7.4 million inhabitants. In those countries offering p-PCI services to the majority of their STEMI patients, this population varied between 0.3 and 1.1 million per centre. In-hospital mortality of all consecutive STEMI patients varied between 4.2 and 13.5%, for patients treated by TL between 3.5 and 14% and for patients treated by p-PCI between 2.7 and 8%. The time reported from symptom onset to the first medical contact (FMC) varied between 60 and 210 min, FMC-needle time for TL between 30 and 110 min, and FMC-balloon time for p-PCI between 60 and 177 min. Conclusion Most North, West, and Central European countries used p-PCI for the majority of their STEMI patients. The lack of organized p-PCI networks was associated with fewer patients overall receiving some form of reperfusion therapy.

Epinephrine Increases the Severity of Postresuscitation Myocardial Dysfunction

BACKGROUND Epinephrine has been the mainstay for cardiac resuscitation for more than 30 years. Its vasopressor effect by which it increases coronary perfusion pressure is likely to favor initial resuscitation. Its beta-adrenergic action, however, may have detrimental effects on postresuscitation myocardial function when administered before resuscitation because it increases myocardial oxygen consumption. In the present study, our focus was on postresuscitation effects of epinephrine when this adrenergic agent was administered during cardiopulmonary resuscitation. Postresuscitation myocardial functions were compared with those of a selective alpha-adrenergic agent, phenylephrine, when epinephrine was combined with a beta 1-adrenergic blocking agent, esmolol, and saline placebo. METHODS AND RESULTS Ventricular fibrillation was induced in 40 Sprague-Dawley rats. Mechanical ventilation and precordial compression was initiated either 4 or 8 minutes after the start of ventricular fibrillation. The adrenergic drug or saline placebo was administered as a bolus after 4 minutes of precordial compression. Defibrillation was attempted 4 minutes later. Left ventricular pressure, dP/dt40, and negative dP/dt were continuously measured for an interval of 240 minutes after successful cardiac resuscitation. Except for saline placebo, comparable increases in coronary perfusion pressure were observed after each drug intervention. The number of countershocks required for restoration of spontaneous circulation was significantly greater for epinephrine-treated animals (10 +/- 8) when compared with phenylephrine-treated animals (1.8 +/- 0.4, P < .01) and with animals treated with epinephrine combined with esmolol (1.6 +/- 0.9, P < .01). After resuscitation, dP/dt40 and negative dP/dt were significantly decreased and left ventricular end-diastolic pressure was significantly increased in each animal when compared with prearrest levels. However, the greatest impairment followed epinephrine, and this was associated with significantly greater heart rate and the shortest interval of postresuscitation survival of 8 +/- 4 hours, whereas placebo controls survived for 12 +/- 11 hours. Phenylephrine-treated animals survived for 41 +/- 10 hours (P < .01 versus epinephrine), and animals that received a combination of epinephrine and esmolol survived for 35 +/- 11 hours (P < .01 versus epinephrine). When the duration of untreated cardiac arrest was increased from 4 to 8 minutes, the severity of postresuscitation left ventricular dysfunction was magnified, but disproportionate decreases in postresuscitation survival were again observed with placebo and epinephrine when compared with alpha-adrenergic agonists. CONCLUSIONS In an established rodent model after resuscitation following cardiac arrest, epinephrine significantly increased the severity of postresuscitation myocardial dysfunction and decreased duration of survival. More selective alpha-adrenergic agonist or blockade of beta 1-adrenergic actions of epinephrine reduced postresuscitation myocardial impairment and prolonged survival.

Early glycoprotein IIb–IIIa inhibitors in primary angioplasty (EGYPT) cooperation: an individual patient data meta-analysis

Background: Even though time-to-treatment has been shown to be a determinant of mortality in primary angioplasty, the potential benefits from early pharmacological reperfusion by glycoprotein (Gp) IIb–IIIa inhibitors are still unclear. The aim of this meta-analysis was to combine individual data from all randomised trials conducted on facilitated primary angioplasty by the use of early Gp IIb–IIIa inhibitors. Methods and results: The literature was scanned by formal searches of electronic databases (MEDLINE, EMBASE) from January 1990 to October 2007. All randomised trials on facilitation by the early administration of Gp IIb–IIIa inhibitors in ST-segment elevation myocardial infarction (STEMI) were examined. No language restrictions were enforced. Individual patient data were obtained from 11 out of 13 trials, including 1662 patients (840 patients (50.5%) randomly assigned to early and 822 patients (49.5%) to late Gp IIb–IIIa inhibitor administration). Preprocedural Thrombolysis in Myocardial Infarction Study (TIMI) grade 3 flow was more frequent with early Gp IIb–IIIa inhibitors. Postprocedural TIMI 3 flow and myocardial blush grade 3 were higher with early Gp IIb–IIIa inhibitors but did not reach statistical significance except for abciximab, whereas the rate of complete ST-segment resolution was significantly higher with early Gp IIb–IIIa inhibitors. Mortality was not significantly different between groups, although early abciximab demonstrated improved survival compared with late administration, even after adjustment for clinical and angiographic confounding factors. Conclusions: This meta-analysis shows that pharmacological facilitation with the early administration of Gp IIb–IIIa inhibitors in patients undergoing primary angioplasty for STEMI is associated with significant benefits in terms of preprocedural epicardial recanalisation and ST-segment resolution, which translated into non-significant mortality benefits except for abciximab.

Effect of short-term treatment with azithromycin on recurrent ischaemic events in patients with acute coronary syndrome in the Azithromycin in Acute Coronary Syndrome (AZACS) trial: a randomised controlled trial

BACKGROUND There is serological and epidemiological evidence of an association between Chlamydia pneumoniae infection and coronary artery disease. Results of previous smaller studies have indicated a reduction of recurrent ischaemic events in patients with acute coronary syndrome when given macrolide antibiotics. We aimed to assess whether short-term treatment with the macrolide antibiotic azithromycin reduces recurrent ischaemic events in patients admitted for unstable angina or myocardial infarction. METHODS We assessed the effect of azithromycin in a multicentre, double-blind randomised trial in 1439 patients with unstable angina or acute myocardial infarction. Patients were randomly allocated to receive 500 mg azithromycin on the first day after randomisation, followed by 250 mg daily for 4 days or placebo. Patients were followed up for 6 months. The primary endpoints were death, recurrent myocardial infarction, or recurrent ischaemia necessitating revascularisation. Analysis was done by intention to treat. FINDINGS Treatment with azithromycin did not result in reduction of either individual endpoints or any of the primary endpoints. Of the 716 patients in the azithromycin group, 23 (3%) died, 17 (2%) developed myocardial infarction, 65 (9%) had recurrent ischaemia needing revascularisation, and 100 (14%) had one or more of these endpoints. In the placebo group (n=723) the corresponding numbers of patients were 24 (4%), 22 (3%), 59 (8%), and 106 (15%), respectively (p=0.664, 95% CI 0.72-1.24). 62 (9%) of patients in the azithromycin group and 59 (8%) in the placebo group reached the secondary endpoint of ischaemia or congestive heart failure necessitating admission (difference 0.5%, 95% CI 0.75-1.53; p=0.707). We recorded few side-effects. INTERPRETATION Short-term treatment with azithromycin does not reduce development of recurrent events in patients with acute coronary syndrome.

Reperfusion therapy for ST elevation acute myocardial infarction 2010/2011: current status in 37 ESC countries

AIMS Primary percutaneous coronary intervention (PPCI) is the preferred reperfusion therapy in ST-elevation myocardial infarction (STEMI). We conducted this study to evaluate the contemporary status on the use and type of reperfusion therapy in patients admitted with STEMI in the European Society of Cardiology (ESC) member countries. METHODS AND RESULTS A cross-sectional descriptive study based on aggregated country-level data on the use of reperfusion therapy in patients admitted with STEMI during 2010 or 2011. Thirty-seven ESC countries were able to provide data from existing national or regional registries. In countries where no such registries exist, data were based on best expert estimates. Data were collected on the use of STEMI reperfusion treatment and mortality, the numbers of cardiologists, and the availability of PPCI facilities in each country. Our survey provides a brief data summary of the degree of variation in reperfusion therapy across Europe. The number of PPCI procedures varied between countries, ranging from 23 to 884 per million inhabitants. Primary percutaneous coronary intervention and thrombolysis were the dominant reperfusion strategy in 33 and 4 countries, respectively. The mean population served by a single PPCI centre with a 24-h service 7 days a week ranged from 31 300 inhabitants per centre to 6 533 000 inhabitants per centre. Twenty-seven of the total 37 countries participated in a former survey from 2007, and major increases in PPCI utilization were observed in 13 of these countries. CONCLUSION Large variations in reperfusion treatment are still present across Europe. Countries in Eastern and Southern Europe reported that a substantial number of STEMI patients are not receiving any reperfusion therapy. Implementation of the best reperfusion therapy as recommended in the guidelines should be encouraged.

Electrocardiographic prediction of the success of cardiac resuscitation

OBJECTIVES To identify a method for predicting the success or failure of a defibrillatory shock such as to avoid potentially detrimental interruptions of cardiopulmonary resuscitation (CPR). Such a method would also guide more optimal programming of automated external defibrillators. DESIGN Prospective, observational animal study. SETTING Medical research laboratory in a university-affiliated research and educational foundation. SUBJECTS Domestic pigs. INTERVENTIONS Ventricular fibrillation (VF) was electrically induced in 66 domestic pigs. After an interval of between 3 and 5 mins of untreated VF, precordial compression was begun. Electrocardiographic lead 2 was monitored and artifacts produced during precordial compression were removed by digital filtering. MEASUREMENTS AND MAIN RESULTS In the derivation study, electrical defibrillation restored spontaneous circulation in 30 of the 66 animals. Successfully resuscitated animals had significantly greater coronary perfusion pressure, maximum VF amplitude, mean VF amplitude, and dominant VF frequency. No animals were resuscitated if the coronary perfusion pressure was <8 mm Hg, maximum amplitude was <0.48 mV, mean amplitude was <0.25 mV, or dominant frequency <9.9 Hz independently of the duration of untreated VF. When mean amplitude and dominant frequency were combined, the predictability was further improved. In an additional validation study of 14 animals, consecutive defibrillations were uniformly unsuccessful if the combination of mean amplitude and dominant frequency did not exceed the threshold values obtained in derivation study. CONCLUSION Mean VF amplitude alone or in combination with dominant frequency of VF was expressed as a numerical score. It served as an objective noninvasive measurement on a par with that of coronary perfusion pressure for predicting the success of defibrillation. As such, it minimizes the detriment of repetitively interrupting mechanical interventions during CPR for electrical defibrillation when an electrical shock predictably fails to restore an effective rhythm.

Early glycoprotein IIb-IIIa inhibitors in primary angioplasty-abciximab long-term results (EGYPT-ALT) cooperation: individual patient's data meta-analysis.

Summary.  Background: Even although time to treatment has been shown to be a determinant of mortality in primary angioplasty, the potential benefits are still unclear from early pharmacological reperfusion by glycoprotein (Gp) IIb‐IIIa inhibitors. Therefore, the aim of this meta‐analysis was to combine individual data from all randomized trials conducted on upstream as compared with late peri‐procedural abciximab administration in primary angioplasty. Methods: The literature was scanned using formal searches of electronic databases (MEDLINE and EMBASE) from January 1990 to December 2010. All randomized trials on upstream abciximab administration in primary angioplasty were examined. No language restrictions were enforced. Results: We included a total of seven randomized trials enrolling 722 patients, who were randomized to early (n = 357, 49.4%) or late (n = 365, 50.6%) peri‐procedural abciximab administration. No difference in baseline characteristics was observed between the two groups. Follow‐up data were collected at a median (25th–75th percentiles) of 1095 days (720–1967). Early abciximab was associated with a significant reduction in mortality (primary endpoint) [20% vs. 24.6%; hazard ratio (HR) 95% confidence interval (CI) = 0.65 (0.42–0.98) P = 0.02, Phet = 0.6]. Furthermore, early abciximab administration was associated with a significant improvement in pre‐procedural thrombolysis in myocardial infarction (TIMI) 3 flow (21.6% vs. 10.1%, P < 0.0001), post‐procedural TIMI 3 flow (90% vs. 84.8%, P = 0.04), an improvement in myocardial perfusion as evaluated by post‐procedural myocardial blush grade (MBG) 3 (52.0% vs. 43.2%, P = 0.03) and ST‐segment resolution (58.4% vs. 43.5%, P < 0.0001) and significantly less distal embolization (10.1% vs. 16.2%, P = 0.02). No difference was observed in terms of major bleeding complications between early and late abciximab administration (3.3% vs. 2.3%, P = 0.4). Conclusions: This meta‐analysis shows that early upstream administration of abciximab in patients undergoing primary angioplasty for ST‐segment elevation myocardial infarction (STEMI) is associated with significant benefits in terms of pre‐procedural epicardial re‐canalization and ST‐segment resolution, which translates in to significant mortality benefits at long‐term follow‐up.

Intravenous amiodarone versus verapamil for acute conversion of paroxysmal atrial fibrillation to sinus rhythm

Abstract Amiodarone and verapamil are well-known antiarrhythmic drugs used for treatment of ventricular and supraventricular arrhythmias. Although verapamil is the drug of choice for control of the atrioventricular node, it has also been reported to terminate atrial fibrillation. 1–3 Amiodarone has been used extensively for drug-refractory ventricular tachycardia but seldom for termination of paroxysmal atrial fibrillation. 4–6 To our knowledge, no comparative study with amiodarone and verapamil has been reported. Because of this, we compared the efficacy of intravenous amiodarone versus verapamil for conversion of paroxysmal atrial fibrillation to sinus rhythm in a single-blind randomized study.

Effects of abciximab pretreatment in patients with acute myocardial infarction undergoing primary angioplasty

In summary, our study indicates that abciximab pretreatment in patients with ST-elevation myocardial infarction may be beneficial because it partially restores epicardial patency before a primary angioplasty attempt and facilitates early ST-segment elevation resolution.

Angiographic characteristics of coronary disease and postresuscitation electrocardiograms in patients with aborted cardiac arrest outside a hospital.

Postresuscitation electrocardiogram (ECG) in patients with aborted cardiac death may demonstrate ST-elevation myocardial infarction (STEMI), ST-T changes, intraventricular conduction delay, or other nonspecific findings. In the present study, we compared ECG to urgent coronary angiogram in 158 consecutive patients with STEMI and 54 patients not fulfilling criteria for STEMI admitted to our hospital from January 1, 2003 through December 31, 2008. At least 1 obstructive lesion was present in 97% of patients with STEMI and in 59% of patients without STEMI with ≥1 occlusion in 82% and 39%, respectively (p <0.001). Obstructive lesion was considered acute in 89% of patients with STEMI and in 24% of patients without STEMI (p <0.001). An acute lesion in STEMI had a higher thrombus score (2.6 vs 1.3, p = 0.05) and more often presented with Thrombolysis In Myocardial Infarction grade 0 to 1 flow (75% vs 36%, p <0.01). Percutaneous coronary intervention, which was attempted in 148 lesions in patients with STEMI and in 17 lesions in patients without STEMI, resulted in final Thrombolysis In Myocardial Infarction grade 3 flow in 87% and 71%, respectively (p = 0.34). In conclusion, STEMI on postresuscitation ECG is usually associated with the presence of an acute culprit lesion. However, in the absence of STEMI, an acute culprit lesion is still present in 1/4 of patients. An acute lesion in STEMI is more thrombotic and more often leads to complete occlusion. Urgent percutaneous coronary intervention is feasible and successful regardless of postresuscitation ECG.