Acute myocardial infarction : early diagnosis and the prognostic value of ECG and echocardiography

Sammanfattning: Introduction Acute myocardial infarction (AMI) is a main cause of death. Despite vast improvements in management and treatment strategies over the past decades, morbidity and mortality after an AMI remains high. For patients with AMI and ST-segment elevations (STEMI), urgent management has been shown to be associated with reductions in both morbidity and mortality. Various pre-hospital management strategies have been implemented, during which STEMI patients can be referred directly to the catheterization laboratory instead of first being assessed in the emergency department. Valuable minutes can thus be saved. However, it is important that the diagnosis is correct which can be more challenging in a setting where the referring cardiologist is not at the same location as the patient and the clinical setting therefore needs to be reported by the paramedic staff. Studies on the accuracy of pre-hospital STEMI diagnoses are limited. In order to expedite management for STEMI patients, international guidelines have included benchmark time targets. Little is known regarding gender differences in the achievement of these time targets, and the feasibility of obtaining a pre-hospital ECG within ten minutes of ambulance arrival has been questioned. For patients who survive an AMI, there is a risk of transient or permanent damage to the left ventricle. Such damage can be quantified by echocardiography. It is shown that patients with a reduced left ventricular ejection fraction (LVEF) have a higher risk of sudden cardiac death than patients with normal LVEF. For patients with reduced LVEF despite optimal medical treatment, an implantable cardioverter defibrillator (ICD) can reduce mortality. This benefit is not seen until after several months have passed since the AMI. This is further complicated by the fact that the risk of death is highest in the early days, weeks and months after an AMI. Therefore, finding predictors in the early phase after an AMI, preferably while the patient is still admitted to the ward, would likely be beneficial in the selection of patients for ICD treatment. Aims The overall aim of this thesis was to find easily obtainable measurements by ECG and echocardiography that could improve the prognosis for patients with acute myocardial infarction. More specifically, the aim was to study the rate of false-positive STEMI diagnoses based on pre-hospital ECGs (study I), study gender differences in time intervals and adherence to guideline set time targets (study II), study the predictive value of low-dose dobutamine stress echocardiography on the improvement of LVEF (study III) and investigate the use of discharge ECG in the early prediction of ICD candidates (study IV). Methods In study I all patients for whom a pre-hospital ECG had been transmitted to the investigating hospital during 2013 were included. In study II, patients with a STEMI diagnosis and a prehospital ECG between December 2010 and July 2015 were included. Information on whether a pre-hospital STEMI diagnosis had been set or not was collected from medical charts and the final diagnosis of STEMI was found in the national quality registry SWEDEHEART. For both study I and study II, information on time intervals were collected from ambulance charts, medical charts, a database collecting information on pre-hospital ECGs, and SWEDEHEART. In studies III and IV, adult patients with an at least moderately reduced left ventricular function (defined as LVEF ≤ 40%) with a life expectancy of more than one year and who were admitted for AMI were invited and followed by clinical visits and echocardiographic examinations. In study III, a low-dose dobutamine stress echocardiogram was performed within one week of the AMI and in study IV, the discharge ECG was reviewed. Results In study I, 16% (95% CI 10 – 23) out of 115 patients with a suspected STEMI based on prehospital ECGs were discharged with alternative diagnoses. Measured as the time from ambulance arrival at the patient’s location, the time target of reperfusion therapy within 90 minutes was achieved for almost all patients (98%), but the achievement of a pre-hospital ECG within ten minutes was only met for 16% of the cohort. The delay time to pre-hospital ECG was significantly longer for women than for men, 20 vs. 13 minutes (p < 0.001). In study II, 539 patients with STEMI and a pre-hospital ECG were included. A pre-hospital ECG was obtained within ten minutes for 22% of the cohort, and the target was more likely to be achieved for men than for women (29% vs. 14%, p = 0.001). Among all patients, 88% reached the target of reperfusion therapy within 90 minutes and there was no difference between men and women. Women had a significantly longer delay time between symptom onset and emergency call than men (median 61 vs. 45 minutes, p = 0.031). In study III, among 96 patients with an at least moderately reduced LVEF after an AMI, 60% had an LVEF ≥ 35% after three months. Patients with an LVEF ≤ 35% after three months had a significantly lower left ventricular function at both resting and stress echocardiography, measured as LVEF, mitral annular plane systolic excursion (MAPSE) and peak systolic velocity (PSV). Baseline LVEF was a good predictor of recovery with a C-statistic of 85% (95% CI 74 – 94). None of the other variables, including the stress echocardiography variables, were better discriminators. In study IV, 87 patients with LVEF ≤ 40% after an AMI were included. Patients who had a pathologic R-wave progression on the discharge ECG were four times more likely to receive an ICD than those with normal R-wave progression (HR 4.0, 95% CI 1.1-14.3, p = 0.033). None of the patients without a pathologic R-wave progression, pathologic Q-waves, or intraventricular conduction abnormalities, received an ICD or suffered from malignant arrhythmias during the follow-up period. Conclusions The rate of false-positive catheterization laboratory activations based on pre-hospital STEMI diagnoses is well in comparison to rates reported based on in-hospital triage. Still, there are gender differences favoring men in regards of delay time from symptom onset to emergency call and ambulance arrival to pre-hospital ECG. The target of obtaining a pre-hospital ECG within ten minutes is met for only around one fifth of the patients, and improvements regarding this are warranted. For patients with heart failure after an AMI, baseline LVEF is a strong predictor of improved recovery while simple measurements of LVEF, MAPSE and PSV during low-dose dobutamine stress echocardiography did not add prognostic information. Patients with a pathologic R-wave progression have a significantly higher risk of receiving an ICD, and patients without pathologic R-wave progression, or Q-waves, or intraventricular conduction abnormalities are unlikely to receive an ICD and could be seen as a low-risk population.