Ulf Näslund

It's time for a change to a troponin standard.

Recently, the European Society of Cardiology (ESC) and the American College of Cardiology (ACC) convened a conference to discuss refinements in the diagnosis of acute myocardial infarction. The panel on biochemistry considered issues related to the use of marker proteins. We were guided predominantly by the science of the area. We were also cognizant of the impact that changes in the standards would have on epidemiology, clinical trials, education of physicians, and patient care. Our recommendations will be incorporated, with the recommendations of the other panels, into a position paper for the ESC and the ACC. However, the members of the biochemistry group decided to express the opinions we felt were important in this area independently. Our thinking does not represent the position of the ESC, the ACC, or of the conjoint task force. Many modifications of the original World Health Organization criteria for acute myocardial infarction1 have been accepted and incorporated into the ESC/ACC criteria; some deletions have also occurred. Until recently, most markers were detected using enzymatic activity; detection of the protein concentration now is preferred. Thus, it is more appropriate to refer to molecules released into the circulation as a consequence of cardiac injury as biochemical diagnostic markers or biomarkers. In this editorial, we emphasize issues related to the biochemical diagnosis of acute myocardial infarction. New and improved plasma biomarkers (troponins) with better sensitivity and specificity will be emphasized in preference to markers such as total creatine kinase (CK), CK-MB, lactate dehydrogenase, and aspartate aminotransferase. Rapid assays for the early detection of infarction that may be helpful will be delineated, and the use of the troponin markers to aid in the risk stratification of patients with acute coronary syndromes will be recommended. ### Biomarker Increases Detectable increases in the biomarkers of cardiac injury are indicative of injury to the …

A long-term perspective on the protective effects of an early invasive strategy in unstable coronary artery disease: Two-year follow-up of the FRISC-II invasive study

OBJECTIVES We sought to report the first and repeat events and to separate spontaneous and procedure-related events over two years in the Fast Revascularization during InStability in Coronary artery disease (FRISC-II) invasive trial. BACKGROUND The FRISC-II invasive trial compared the long-term effects of an early invasive versus noninvasive strategy, in terms of death and myocardial infarction (MI) and the need for repeat hospital admissions and late revascularization procedures in patients with coronary artery disease (UCAD). METHODS In the FRISC-II trial, 2,457 patients with UCAD were randomized to an early invasive or noninvasive strategy. RESULTS At 24 month follow-up, there were reductions in mortality (n = 45 [3.7%] vs. 67 [5.4%]; risk ratio 0.68 [95% confidence interval (CI) 0.47 to 0.98]; p = 0.038), MI (n = 111 [9.2%] vs. 156 [12.7%]; risk ratio 0.72 [95% CI 0.57 to 0.91]; p = 0.005), and the composite end point of death or MI (n = 146 [12.1%] vs. 200 [16.3%]; risk ratio 0.74 [95% CI 0.61 to 0.90]; p = 0.003) in the invasive compared with the noninvasive group. Procedure-related MIs were two to three times more common, but spontaneous ones were three times less common in the invasive than in the noninvasive group. After the first year, there was no difference in mortality (n = 20 [1.7%]) between the two groups and fewer MIs in the invasive group (p = 0.031). CONCLUSIONS In UCAD, the early invasive approach leads to a sustained reduction in mortality, cardiac morbidity, and the need for repeat hospital admissions and late revascularization procedures. Although the benefits are greatest during the first months, during the second year, cardiac morbidity is lower and the need for hospital care is less in the invasive group.

Signs of myocardial ischaemia after injection of oxytocin: a randomized double-blind comparison of oxytocin and methylergometrine during Caesarean section

BACKGROUND ECG changes, similar to those seen during myocardial ischaemia, together with symptoms of chest pain, are common during Caesarean section (CS). We hypothesized that oxytocin administration has cardiovascular effects leading to these symptoms and ECG changes. METHODS Forty women undergoing elective CS under spinal anaesthesia were given an i.v. bolus of either 10 IU of oxytocin (Group OXY-CS, n=20) or 0.2 mg of methylergometrine (Group MET-CS, n=20), in a double-blind, randomized fashion after delivery. Ten healthy, non-pregnant, non-anaesthetized women were used as normal controls (Group OXY-NC, n=10) and were given 10 IU of oxytocin i.v. Twelve-lead ECG, on-line, computerized vectorcardiography (VCG), and invasive arterial pressure were recorded. RESULTS Oxytocin produced a significant increase in heart rate, +28 (SD 4) and +52 (3) beats min(-1) [mean (SEM); P<0.001], decreases in mean arterial pressure, -33 (2) and -30 (3) mm Hg (P<0.001), and increases in the spatial ST-change vector magnitude (STC-VM), +77 (12) and +114 (8) microV (P<0.001), in CS patients and controls, respectively. Symptoms of chest pain and subjective discomfort were simultaneously present. Methylergometrine produced mild hypertension and no significant ECG changes. CONCLUSIONS Oxytocin administered as an i.v. bolus of 10 IU induces chest pain, transient profound tachycardia, hypotension, and concomitant signs of myocardial ischaemia according to marked ECG and STC-VM changes. The effects are related to oxytocin administration and not to pregnancy, surgical procedure, delivery, or sympathetic block from spinal anaesthesia.

Superoxide dismutase and catalase reduce infarct size in a porcine myocardial occlusion-reperfusion model

We investigated if superoxide dismutase and catalase could reduce myocardial infarct size in an open chest occlusion-reperfusion model. Thirty pigs were used for the experiment. The left anterior descending artery was ligated for 60 min followed by a 5 h reperfusion period. After randomisation and blinding the two enzymes or placebo were injected into the left atrium as a bolus immediately before and at the end of the occlusion and as a continuous infusion over the first hour of the reperfusion period. The total dose for each enzyme was 8 mg/kg bw. Tetrazolium staining was used to determine infarct size. The study code was not broken until all calculations and exclusions had been made. Nine animals died from intractable ventricular fibrillation, most commonly during the occlusion. Another three were excluded for technical reasons. We found that superoxide dismutase and catalase reduced infarct size in relation to myocardium at risk from a mean of 89% to 63% (P less than 0.01). Initial plasma half life for the two enzymes after the bolus infusions were calculated to be 30 min.

Gender differences in trends of acute myocardial infarction events : the Northern Sweden MONICA study 1985 - 2004.

BackgroundThe registration of non-fatal and fatal MI events initiated 1985 in the WHO MONICA project has been ongoing in northern Sweden since the end of the WHO project in 1995. The purpose of the present study was to analyze gender differences in first and recurrent events, case fatality and mortality in myocardial infarction (MI) in Northern Sweden during the 20-year period 1985 – 2004.MethodsDiagnosed MI events in subjects aged 25–64 years in the Counties of Norrbotten and Västerbotten were validated according to the MONICA protocol. The total number of events registered up to January 1, 2005 was 11,763: 9,387 in men and 2,376 in women.ResultsThe proportion of male/female events has decreased from 5.5:1 to 3:1. For males the reductions were 30% and 70% for first and recurrent MI, respectively, and for women 0% and 40% in the 55–64 year group. For both sexes a 50% reduction in 28-day case fatality was seen in the 25–64 year-group. Mortality was reduced by 69% and 45% in men and women, respectively.ConclusionFirst and recurrent events of myocardial infarction was markedly reduced in men over the 20-year observation period, but for women the reduction was seen only for recurrent infarctions. Case fatality, on the other hand, was markedly reduced for both sexes. As a result of the positive effects on incidence and case fatality a substantial reduction was seen in total mortality, most pronounced for men.

Limitation of myocardial infarct size by superoxide dismutase as an adjunct to reperfusion after different durations of coronary occlusion in the pig.

Superoxide dismutase (SOD) has been documented to limit myocardial infarct size in the richly collateralized dog heart. This study was designed to explore this concept in a low-collateralized animal model. A blind, randomized, placebo-controlled protocol was used in 65 pentobarbital-anesthetized pigs subjected to closed-chest left anterior descending coronary artery occlusion for 30 (n = 22), 60 (n = 22), and 90 (n = 14) minutes followed by reperfusion up to 24 hours from the start of occlusion. Another seven control pigs were subjected to 24 hours of permanent occlusion. A total dose of 9 mg/kg bovine CuZn SOD was administered as a bolus injection immediately before reperfusion followed by a 1-hour infusion. Infarct size was assessed by tetrazolium staining. Myocardium at risk and collateral flow were determined by using cerium-141-labeled microspheres (15 microns) during the occlusion. After 30 minutes of occlusion, infarct sizes in placebo versus SOD-treated animals were 45.5 +/- 15.7% vs. 23.8 +/- 15.6% of myocardium at risk (p = 0.007). The corresponding values after 60 minutes of occlusion were 78.6 +/- 9.3% vs. 66.9 +/- 14.6% (p = 0.035). SOD administered after 90 minutes of occlusion did not limit infarct size (88.5 +/- 4.8% vs. 92.3 +/- 5.2%). Twenty-four hours of coronary occlusion resulted in infarction of 92.4 +/- 4.2% of myocardium at risk. (All values are mean +/- SD.) Ventricular fibrillation occurred in only nine pigs distributed equally between SOD and placebo. The results indicate that CuZn SOD has the potential to further improve the myocardial salvage established by reperfusion of an ischemic pig heart territory. However, the narrow time window for limiting infarct size in the pig by reperfusion is not much extended by SOD.

Trans-catheter aortic valve implantation – early recovery of left and preservation of right ventricular function

This study aimed to assess the early effect of trans-catheter aortic valve implantation (TAVI) on right (RV) and left ventricular (LV) function in severe aortic stenosis (AS) patients. Twenty AS patients (age 79±6 years) were examined before, one week and six weeks after TAVI using Doppler echocardiography. LV ejection fraction (EF), long-axis [mitral annular plane systolic excursion (MAPSE)] and RV long-axis [tricuspid annular plane systolic excursion (TAPSE)] function, septal radial motion were studied. Results were compared with 30 AS patients before and one week after aortic valve replacement (AVR) as well as 30 normals (reference group). Before TAVI, LVEF was reduced and E/A was higher than the reference and AVR groups (P<0.05 for all). MAPSE, TAPSE and septal motion were equally reduced in TAVI and AVR patients (P<0.05 for all). One week after the TAVI, EF increased in patients with values <50% before the procedure. In contrast, AVR resulted in reversed septal motion (P<0.001) and depressed TAPSE (P<0.001). The extent of reversed septal motion correlated with that of TAPSE in the patients group as a whole after procedures (r=0.78, P<0.001). Six weeks after TAVI, RV function remained unchanged, but LVEF increased and E/A decreased (P<0.05 for both). Thus, TAVI procedure results in significant early improvement of LV systolic and diastolic function particularly in patients with reduced EF and preserves RV systolic function.

Better long-term survival in young and middle-aged women than in men after a first myocardial infarction between 1985 and 2006. an analysis of 8630 patients in the Northern Sweden MONICA Study

BackgroundThere is conflicting and only scant evidence on the effect of gender on long-term survival after a myocardial infarction (MI). Our aim was to analyse sex-specific survival of patients for up to 23 years after a first MI in northern Sweden and to describe time trends.MethodsThe Northern Sweden MONICA Myocardial Infarction Registry was linked to The Swedish National Cause of Death Registry for a total of 8630 patients, 25 to 64 years of age, 6762 men and 1868 women, with a first MI during 1985-2006. Also deaths before admission to hospital were included. Follow-up ended on August 30, 2008.ResultsMedian follow-up was 7.1 years, maximum 23 years and the study included 70 072 patient-years. During the follow-up 45.3% of the men and 43.7% of the women had died. Median survival for men was 187 months (95% confidence interval (CI) 179-194) and for women 200 months (95% CI 186-214). The hazard ratio (HR) for all cause mortality after adjustment for age group was 1.092 (1.010-1.18, P = 0.025) males compared to females, i.e. 9 percent higher survival in women. After excluding subjects who died before reaching hospital HR declined to 1.017 (95%CI 0.93-1.11, P = 0.7). For any duration of follow-up a higher proportion of women were alive, irrespective of age group. The 5-year survivals were 75.3% and 77.5%, in younger (<57 years) men and women and were 65.5% and 66.3% in older (57-64 years) men and women, respectively. For each of four successive cohorts survival improved. Survival time was longer for women than for men in all age groups.ConclusionsAge-adjusted survival was higher among women than men after a first MI and has improved markedly and equally in both men and women over a 23-year period. This difference was due to lower risk for women to die before reaching hospital.

Clinical significance of abnormal T waves in patients with non–ST-segment elevation acute coronary syndromes☆

T-wave abnormalities are common electrocardiographic occurrences in patients with non-ST-segment elevation acute coronary syndromes. Although these abnormalities are considered relatively benign, physicians use them to guide therapies. The study objective was to examine the prognostic predictive information of T-wave abnormalities in the setting of unstable coronary artery disease. The T-wave abnormality criterion was based on a new set of normal T-wave amplitude limits differentiated by gender, age, electrocardiographic lead, and QRS axis. Four hundred sixty-eight patients suspected of an acute ischemic incident and considered ineligible for reperfusion therapy were included. Thirteen categories of T-wave abnormalities were tested prospectively. The primary 30-day end point was the combination of refractory angina, myocardial infarction, or death. Quantitative T-wave analysis in an electrocardiographic core laboratory revealed 6 of 13 prespecified categories of T-wave abnormalities that were significantly associated with an adverse outcome. T-wave abnormalities had no prognostic value when ST-segment depression was also present, but this occurred in only 7.9% of patients. T-wave abnormalities as the sole manifestation of ischemia were common (74.4%). Patients with abnormal T waves in > or =1 of 6 selected abnormality categories (70.3%) had a significantly higher risk of death, acute myocardial infarction, and refractory angina (11% vs 3%; p = 0.018). Thus, T-wave abnormalities in patients presenting with non-ST-segment elevation acute coronary syndromes are common and should not automatically be regarded as benign phenomena. Quantitative T- wave analysis provides optimal risk stratification.

On-Line Computerized Vectorcardiography: Influence of Body Position, Heart Rate, Radiographic Contrast Fluid and Myocardial Ischemia

UNLABELLED On-line computerized vectorcardiography (cVCG) is increasingly being used for continuous monitoring of myocardial ischemia, however, little is known about factors other than ischemia causing electrocardiographic abnormalities. This paper describes how three important cVCG parameters, STC-VM, ST-VM and QRS-VD, are affected by different body positions, myocardial ischemia, contrast injection and increasing heart rate in patients with and without coronary artery disease. The main findings of the study are: contrast injection and different body positions caused major changes in QRS-VD but affected ST-VM and STC-VM to a minor degree. Increasing heart rate by atrial pacing produced substantial changes in all three parameters. Ischemia during angioplasty also produced changes in all three parameters, STC-VM being the most sensitive parameter. IN CONCLUSION (1) STC-VM (> or = 50 microV) is the most valuable parameter for monitoring ischemia; (2) we propose ST-VM > or = 50 microV as criterion instead of previously used 25 microV; (3) QRS-VD cannot be used as a single marker of ischemia, and (4) electrocardiographic changes induced by increased heart rate should be taken into account during interpretation.