Improving diagnosis, reperfusion therapy and secondary prevention in acute myocardial infarction

The total ischemic time has an important prognostic effect on the outcome of patients with a ST elevation acute myocardial infarction. As patient delays are less modifiable it is most important to reduce as much as possible all components of the system delay during the pre-hospital and in-hospital phase.1 This is again confirmed by the results of a large Israeli STEMI registry that showed that the greater utilization of mobile intensive care units during the last decade was associated with increased primary reperfusion rates and a reduction in door-to-reperfusion therapy system delay, as well as the total ischemic time in patients undergoing primary reperfusion resulting in a reduced one-year adjusted mortality.2 Although primary percutaneous coronary intervention (PCI) is the preferred reperfusion method a fibrinolysis-based pharmaco-invasive strategy remains a viable and important reperfusion option in geographically difficult to reach areas where a timely performed primary PCI is not possible. In a secondary analysis of the STREAM trial STEMI patients included at community hospitals had similar outcomes compared to prehospital assigned patients despite a higher baseline risk with no difference between a primary PCI or the pharmaco-invasive strategy.3 However, patients at community hospitals with a failed fibrinolytic therapy requiring rescue PCI had a worse in-hospital and 1-year outcome than patients with a failed fibrinolysis at a tertiary hospital. These findings indicate that all patients in whom for logistic reasons a pharmaco-invasive strategy is considered should immediately be transferred to a PCI-capable hospital. Early infarct-related artery patency has been associated with improved outcomes in STEMI patients treated with PCI. Data from the EUROMAX trial show that despite major changes in contemporary primary PCI strategies (including wider use of pre-hospital pharmacotherapy, use of more potent antithrombotic agents and newer stents), early infarct-related artery patency is still associated with higher procedural success and improved clinical outcomes.4 However, it is important to note that there was no interaction between the applied antithrombotic strategy and the benefits of a patent infarct-related artery at presentation. Randomized controlled trials and registries have provided conflicting results regarding procedural and clinical outcomes of thrombus aspiration combined with PCI, when compared with primary PCI alone in STEMI patients. Data from a large contemporary Swiss registry of acute coronary syndrome patients shows that PCI with thrombus aspiration did not result in an improved restoration of coronary blood flow immediately after the procedure.5 Furthermore, changes in cardiac troponins and clinical outcomes at either 30 days or 1 year were similar in patients treated by PCI with thrombus aspiration or by PCI alone. Prescription of high-intensity statins as early as possible after acute myocardial infarction is an essential part of secondary prevention of ischemic heart disease. In a consensus document from the French group the recommendations and practical implementation of lipid lowering therapy after acute coronary syndrome are reviewed.6 Any increase in circulating troponin is perceived as expression of myocardial injury or necrosis. It is unknown if severe ischemia as induced during stress testing may result in sufficient injury to induce release of troponin. In a study from Pisa the majority of patients (72%) who underwent exercise testing or dobutamine stress echocardiography showed a significant increase of high sensitivity cardiac troponin T (hs-cTnT).7 These increases were however not related to the presence or absence of inducible ischemia and were also observed in patients without obstructive coronary artery disease. Left ventricular hypertrophy was the strongest factor predicting a rise of hs-cTnT. Plasma release of troponin depends on multiple pathogenetic mechanisms, making the biomarker a not reliable tool in detecting transient ischemia. The different pathogenetic processes that may lead to cardiac troponin release from injured myocardium is explained in a short review in this issue.8 It is proposed that besides by myocardial necrosis cardiac troponin release may also be caused by reversible myocardial injury or by chronic myocardial apoptosis. Fatty acid binding protein 4 (FABP4) is not only an intracellular protein, but also a secreted adipokine that contributes to obesity-related metabolic complications. In a small prospective study FABP4 levels were significantly elevated during the early hours after the onset of acute myocardial infarction and were markedly increased in out of hospital cardiac arrest survivor.9 As FABP4 is released by adipocytes via stimulation of a beta-receptor it is hypothesized that its increase in serum serum FABP4 may represent the adrenergic overdrive that accompanies acute myocardial infarction. Copeptin, a marker of endogenous stress, rises very early in acute myocardial infarction whereas cardiac troponin is released in a slower time related fashion from the injured myocardium. A dual marker diagnostic strategy based on the measurement of copeptin and cardiac troponins infarction has therefore a strong pathophysiological rationale in ruling out myocardial infarction. When combined with sensitive or high sensitive cardiac troponin assays a dual marker diagnostic strategy with copeptin provides only very small incremental diagnostic value and is therefore only recommended if older less sensitive troponin assays are used.10 Finally, in an educational review the biochemical, pathophysiological and analytical background of cardiac troponin release not related to ischemic myocardial injury is discussed starting from three clinical scenarios.11