Per Johanson

Association Between Adoption of Evidence-Based Treatment and Survival for Patients With ST-Elevation Myocardial Infarction

CONTEXT Only limited information is available on the speed of implementation of new evidence-based and guideline-recommended treatments and its association with survival in real life health care of patients with ST-elevation myocardial infarction (STEMI). OBJECTIVE To describe the adoption of new treatments and the related chances of short- and long-term survival in consecutive patients with STEMI in a single country over a 12-year period. DESIGN, SETTING, AND PARTICIPANTS The Register of Information and Knowledge about Swedish Heart Intensive Care Admission (RIKS-HIA) records baseline characteristics, treatments, and outcome of consecutive patients with acute coronary syndrome admitted to almost all hospitals in Sweden. This study includes 61,238 patients with a first-time diagnosis of STEMI between 1996 and 2007. MAIN OUTCOME MEASURES Estimated and crude proportions of patients treated with different medications and invasive procedures and mortality over time. RESULTS Of evidence-based treatments, reperfusion increased from 66% (95%, confidence interval [CI], 52%-79%) to 79% (95% CI, 69%-89%; P < .001), primary percutaneous coronary intervention from 12% (95% CI, 11%-14%) to 61% (95% CI, 45%-77%; P < .001), and revascularization from 10% (96% CI, 6%-14%) to 84% (95% CI, 73%-95%; P < .001). The use of aspirin, clopidogrel, β-blockers, statins, and angiotensin-converting enzyme (ACE) inhibitors all increased: clopidogrel from 0% to 82% (95% CI, 69%-95%; P < .001), statins from 23% (95% CI, 12%-33%) to 83% (95% CI, 75%-91%; P < .001), and ACE inhibitor or angiotensin II receptor blockers from 39% (95% CI, 26%-52%) to 69% (95% CI, 58%-70%; P < .001). The estimated in-hospital, 30-day and 1-year mortality decreased from 12.5% (95% CI, 4.3%-20.6%) to 7.2% (95% CI, 1.7%-12.6%; P < .001); from 15.0% (95% CI, 6.2%-23.7%) to 8.6% (95% CI, 2.7%-14.5%; P < .001); and from 21.0% (95% CI, 11.0%-30.9%) to 13.3% (95% CI, 6.0%-20.4%; P < .001), respectively. After adjustment, there was still a consistent trend with lower standardized mortality over the years. The 12-year survival analyses showed that the decrease of mortality was sustained over time. CONCLUSION In a Swedish registry of patients with STEMI, between 1996 and 2007, there was an increase in the prevalence of evidence-based treatments. During this same time, there was a decrease in 30-day and 1-year mortality that was sustained during long-term follow-up.

Troponin T Percentiles from a Random Population Sample, Emergency Room Patients and Patients with Myocardial Infarction

BACKGROUND High-sensitivity cardiac troponin T (cTnT) assays detect small clinically important myocardial infarctions (MI) but also yield higher rates of false-positive results owing to increased concentrations sometimes present in patients without MI. Better understanding is needed of factors influencing the 99th percentile of cTnT concentrations across populations and the frequency of changes in cTnT concentrations >20% often used in combination with increased cTnT concentrations for diagnosis of MI. METHODS cTnT percentiles were determined by use of the Elecsys® hscTnT immunoassay (Modular® Analytics E170) in a random population sample, in emergency room (ER) patients, and in patients with non-ST-elevation MI (NSTEMI). Changes in cTnT concentrations were determined in hospitalized patients without MI. RESULTS The 99th cTnT percentile in a random population sample (median age, 65 years) was 24 ng/L. In ER patients <65 years old without obvious conditions that increase cTnT, the 99th cTnT percentile was 12 ng/L with little age dependence, whereas in those >65 years old it was 82 ng/L and highly age dependent. In hospitalized patients without MI the 97.5th percentile for change in the cTnT concentration was 51%-67%. cTnT remained below the 99th percentile (12 ng/L) in 1% of patients with NSTEMI until 8.5 h after symptom onset and 6 h after ER arrival. CONCLUSIONS Age >65 years was the dominant factor associated with increased cTnT in ER patients. This age association was more prominent in ER patients than in a random population sample. Changes in serial cTnT concentrations >20% were common in hospitalized patients without MI.

Prognostic value of ST-segment resolution—when and what to measure

AIMS Analyses of ST-segment resolution during acute myocardial infarction has, during recent years, challenged coronary angiography as gold-standard for predicting myocardial reflow and future risk. We have previously reported that continuous ST-monitoring can be done accurately in the clinical setting. We now set out to compare the prognostic value of previously suggested cut-offs for ST-segment resolution, and determine the times to measure these. METHODS AND RESULTS We analysed 752 patients with ST-elevation infarction, from the second Assessment of Safety and Efficacy of a New Thrombolytic (ASSENT 2) and ASSENT-PLUS studies, either with vectorcardiography or continuous 12-lead ST-monitoring. All analyses were made blindly by two independent observers. Times to 20, 30, 50 and 70% ST-segment resolution were examined in relation to 30-day mortality.The optimal cut-off for ST-segment resolution analyses was found to be 50%, measured at 60 min. We could hereby identify a large low-risk group, 40% of the population, with only 1.4% 30-day mortality. Furthermore, 88% of deaths were correctly predicted within 1h of observation and treatment. CONCLUSION Continuous ST-monitoring of patients with acute myocardial infarction yields important prognostic information after 60 min of observation and should be used for very early-risk stratification in these patients.

Small Changes in Troponin T Levels Are Common in Patients With Non–ST-Segment Elevation Myocardial Infarction and Are Linked to Higher Mortality

OBJECTIVES The purpose of this study was to examine the extent of change in troponin T levels in patients with non-ST-segment elevation myocardial infarction (NSTEMI). BACKGROUND Changes in cardiac troponin T (cTnT) levels are required for the diagnosis of NSTEMI, according to the new universal definition of acute myocardial infarction. A relative change of 20% to 230% and an absolute change of 7 to 9 ng/l have been suggested as cutoff points. METHODS In a clinical setting, where a change in cTnT was not mandatory for the diagnosis of NSTEMI, serial samples of cTnT were measured with a high-sensitivity cTnT (hs-cTnT) assay, and 37 clinical parameters were evaluated in 1,178 patients with a final diagnosis of NSTEMI presenting <24 h after symptom onset. RESULTS After 6 h of observation, the relative change in the hs-cTnT level remained <20% in 26% and the absolute change <9 ng/l in 12% of the NSTEMI patients. A relative hs-cTnT change <20% was linked to higher long-term mortality across quartiles (p = 0.002) and in multivariate analyses (hazard ratio: 1.61 [95% confidence interval: 1.17 to 2.21], p = 0.004), whereas 30-day mortality was similar across quartiles of relative hs-cTnT change. CONCLUSIONS Because stable hs-TnT levels are common in patients with a clinical diagnosis of NSTEMI in our hospital, a small hs-cTnT change may not be useful to exclude NSTEMI, particularly as these patients show both short-term and long-term mortality at least as high as patients with large changes in hs-cTnT.

Effects of ischemic preconditioning and arterial collateral flow on ST-segment elevation and QRS complex prolongation in a canine model of acute coronary occlusion

BACKGROUND During acute myocardial infarction, both ST elevation and QRS distortion on the initial electrocardiogram (ECG) have been correlated with poorer prognosis. Studies in dogs and humans suggest that these ECG markers provide information about myocardial protection from both collateral blood flow and ischemic preconditioning. METHODS In a protocol designed to precondition the heart with ischemia, we examined both ST-segment elevation and QRS complex prolongation in lead II of the ECG in 23 mongrel dogs during the first and fourth episode of 5 minutes of left circumflex artery occlusion. Myocardial collateral flow was measured during each of these episodes by injection of radioactive microspheres 2.5 minutes into the episode of ischemia. RESULTS During ischemia, the degree of elevation of the ST segments was reduced markedly in hearts preconditioned with ischemia and/or in hearts with the greatest amounts of collateral arterial flow. During the first episode of ischemia, the ST segments increased to a similar extent in severe and moderate ischemia, but less in hearts in which the ischemia was mild. However, marked QRS prolongation was present only in hearts with severe ischemia, and decreased when the hearts were preconditioned. In addition, large ischemic beds exhibited the most marked QRS prolongation, whereas small but even severely ischemic beds showed little or no change in QRS duration. CONCLUSION Both ST elevation and QRS prolongation are reduced by the presence of collateral flow and ischemic preconditioning. The QRS complex merits further study as an important marker of the degree of myocardial protection during human acute myocardial ischemia/infarction.

Admission N-terminal pro-brain natriuretic peptide and its interaction with admission troponin T and ST segment resolution for early risk stratification in ST elevation myocardial infarction

Objective: To assess the long term prognostic value of N-terminal pro-brain natriuretic peptide (NT-proBNP) on admission and its prognostic interaction with both admission troponin T (TnT) concentrations and resolution of ST segment elevation in fibrinolytic treated ST elevation myocardial infarction (STEMI). Design and setting: Substudy of the ASSENT (assessment of the safety and efficacy of a new thrombolytic) -2 and ASSENT-PLUS trials. Patients: NT-proBNP and TnT concentrations were determined on admission in 782 patients. According to NT-proBNP concentrations, patients were divided into three groups: normal concentration (for patients ⩽ 65 years, ⩽ 184 ng/l and ⩽ 268 ng/l and for those > 65 years, ⩽ 269 ng/l and ⩽ 391 ng/l in men and women, respectively); higher than normal but less than the median concentration (742 ng/l); and above the median concentration. For TnT, a cut off of 0.1 μg/l was used. Of the 782 patients, 456 had ST segment resolution (< 50% or ⩾ 50%) at 60 minutes calculated from ST monitoring. Main outcome measures: All cause one year mortality. Results: One year mortality increased stepwise according to increasing concentrations of NT-proBNP (3.4%, 6.5%, and 23.5%, respectively, p < 0.001). In receiver operating characteristic analysis, NT-proBNP strongly trended to be associated more with mortality than TnT and time to 50% ST resolution (area under the curve 0.81, 95% confidence interval (CI) 0.72 to 0.9, 0.67, 95% CI 0.56 to 0.79, and 0.66, 95% CI 0.56 to 0.77, respectively). In a multivariable analysis adjusted for baseline risk factors and TnT, both raised NT-proBNP and ST resolution < 50% were independently associated with higher one year mortality, whereas raised TnT contributed independently only before information on ST resolution was added to the model. Conclusion: Admission NT-proBNP is a strong independent predictor of mortality and gives, together with 50% ST resolution at 60 minutes, important prognostic information even after adjustment for TnT and baseline characteristics in STEMI.

Clinical utility of serial and continuous ST-segment recovery assessment in patients with acute ST-elevation myocardial infarction: assessing the dynamics of epicardial and myocardial reperfusion.

Acute ST-segment–elevation myocardial infarction (STEMI) is a global source of mortality and morbidity and consequently is one of the most active areas of applied research. In the face of multiple reports of new combinations of medical and interventional therapies, the challenge to the clinician is both to understand data from key clinical trials and to translate that understanding to the individual patient at the bedside. STEMI is defined by “ST elevation” on the ECG, which is the electrical manifestation of the pathophysiological changes that follow a thrombotic occlusion of an epicardial coronary artery.1 The ECG is ubiquitous in cardiology, applied as a diagnostic, prognostic, and management tool. Although a single ECG presents about 10 seconds of waveform morphology, acute STEMI displays its dynamic behavior over time, both spontaneously and in response to therapy. The systematic use of serial and continuous ECG assessments has been one of the most fertile areas of advancement in the ability to measure and thereby recognize the presence, speed, quality, and stability of reperfusion of an infarct artery. In addition to providing insights into pathophysiological mechanisms and novel therapies in research protocols, serial or continuous use of this simple, noninvasive, quantitative measure has the potential to guide clinicians through the dynamic events surrounding the management of STEMI patients’ disease. This is illustrated in the following case studies of 3 patients, all of whom presented with 3 hours of chest pain with angiographically documented Thrombolysis in Myocardial Infarction (TIMI) 3 flow, were managed with serial ECGs for clinical purposes, and were simultaneously monitored for research protocols with “black box” continuous 12-lead ECG monitors. ### Patient 1 G.E. was a 67-year-old man with a history of hypertension and tobacco use who presented with 3 hours of chest pain. The initial ECG showed anterolateral ST-segment elevation with a maximum of 15 …

Inequalities in the early treatment of women and men with acute chest pain

PURPOSE The aim of this study was to identify sex differences in the early chain of care for patients with chest pain. DESIGN This is a retrospective study performed at 3 centers including all patients admitted to the emergency department because of chest pain, during a 3-month period in 2008, in the municipality of Göteborg. Chest pain or discomfort in the chest was the only inclusion criterion. There were no exclusion criteria. DATA SOURCES Data were retrospectively collected from ambulance and medical records and electrocardiogram (ECG), echocardiography, and laboratory databases. MAIN FINDINGS A total of 2588 visits (1248 women and 1340 men) made by 2393 patients were included. When adjusting for baseline variables, female sex was significantly associated with a prolonged delay time (defined as above median) between (a) admission to hospital and admission to a hospital ward (odds ratio [OR], 1.59; 95% confidence interval [CI], 1.25-2.03), (b) first physical contact and first dose of aspirin (OR, 2.22; 95% CI, 1.30-3.82), and (c) admission to hospital and coronary angiography (OR, 2.50; 95% CI, 1.29-5.13). Delay time to the first ECG recording did not differ significantly between women and men. PRINCIPAL CONCLUSIONS Among patients hospitalized due to chest pain, when adjusting for differences at baseline, female sex was associated with a prolonged delay time until admission to a hospital ward, to administration of aspirin, and to performing a coronary angiography. There was no difference in delay to the first ECG recording.

Clinical implications of early St-segment variability. A report from the Assent 2 St-monitoring sub-study

ObjectivesEvolution of the ST‐segment during acute myocardial infarction has been shown to yield more information on prognosis than invasive measurements. By continuous ST‐monitoring even very occasional dynamic changes can be analysed. We have recently suggested these variations to be of prognostic importance and possibly reflect individual abilities to deal with a vascular event. We wanted to confirm these findings. MethodsFour hundred and forty‐eight patients were included in the vectorcardiographic sub‐study of the second Assessment of Safety and Efficacy of a New Thrombolytic (ASSENT 2) trial. Patients underwent 24 h of ST‐monitoring. ST‐trend curves were blindly analysed by two independent observers. ResultsST‐variability, defined as an increase of the ST‐segment shift of ≥ 25 μV for 2 min or more, was found to predict death, reinfarction at 30 days or urgent revascularization. By combining variability with resolution of the ST‐segment elevation we could identify a high‐risk group with 9.9%, and a low‐risk group with only 0.8% 30‐day mortality. Hypertensive patients, suggested to have an impaired secretion of endogenous t‐PA, expressed significantly more ST‐variability, possibly a non‐invasive marker of impaired capability of dissolving and preventing thrombi. ConclusionSmall variations in ST‐segment shift during the first 4 h of acute myocardial infarction predict worse outcome.

ST variability during the first 4 hours of acute myocardial infarction predicts 1-year mortality.

Background: Early and complete myocardial reperfusion is the goal when treating a patient with acute myocardial infarction. To achieve this in each individual, an on‐line, accurate, easily handled and preferably noninvasive technique to monitor flow alterations is needed. Recurrent ST‐segment elevation has been shown to reflect cyclic disturbances in perfusion.