Clinical value and cost analysis of the sFlt-1/PlGF ratio in addition to the spot urine protein/creatinine ratio in women with suspected pre-eclampsia: PREPARE cohort study.

BACKGROUND: This study investigated the clinical value of adding the sFlt-1/PlGF ratio to the spot urine protein/creatinine ratio (PCr) in women with suspected pre-eclampsia. METHODS: This was a prospective cohort study performed in a tertiary referral centre. Based on the combination of PCr (< 30) and sFlt-1/PlGF (≤38) results, four groups were described: a double negative result, group A-/-; a negative PCr and positive sFlt-1/PlGF, group B-/+; a positive PCr and negative sFlt-1/PlGF, group C+/-; and a double positive result, group D+/+. The primary outcome was the proportion of false negatives of the combined tests in comparison with PCr alone in the first week after baseline. Secondary, a cost analysis comparing the costs and savings of adding the sFlt-1/PlGF ratio was performed for different follow-up scenarios. RESULTS: A total of 199 women were included. Pre-eclampsia in the first week was observed in 2 women (2%) in group A-/-, 12 (26%) in group B-/+, 4 (27%) in group C+/-, and 12 (92%) in group D+/+. The proportion of false negatives of 8.2% [95% CI 4.9-13.3] with the PCr alone was significantly reduced to 1.6% [0.4-5.7] by adding a negative sFlt-1/PlGF ratio. Furthermore, the addition of the sFlt-1/PlGF ratio to the spot urine PCr, with telemonitoring of women at risk, could result in a reduction of 41% admissions and 36% outpatient visits, leading to a cost reduction of €46,- per patient. CONCLUSIONS: Implementation of the sFlt-1/PlGF ratio in addition to the spot urine PCr, may lead to improved selection of women at low risk and a reduction of hospital care for women with suspected pre-eclampsia. TRIAL REGISTRATION: Netherlands Trial Register (NL8308).

Rational selection of a biomarker panel targeting unmet clinical needs in kidney injury.

The pipeline of biomarker translation from bench to bedside is challenging and limited biomarkers have been adopted to routine clinical care. Ideally, biomarker research and development should be driven by unmet clinical needs in health care. To guide researchers, clinical chemists and clinicians in their biomarker research, the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) has developed a structured questionnaire in which the clinical gaps in current clinical pathways are identified and desirable performance specifications are predefined. In kidney injury, the high prevalence of the syndrome acute kidney injury (AKI) in the hospital setting has a significant impact on morbidity, patient survival and health care costs, but the use of biomarkers indicating early kidney injury in daily patient care remains limited. Routinely, medical labs measure serum creatinine, which is a functional biomarker, insensitive for detecting early kidney damage and cannot distinguish between renal and prerenal AKI. The perceived unmet clinical needs in kidney injury were identified through the EFLM questionnaire. Nephrologists within our tertiary care hospital emphasized that biomarkers are needed for (1) early diagnosis of in-hospital AKI after a medical insult and in critically ill patients, (2) risk stratification for kidney injury prior to a scheduled (elective) intervention, (3) kidney injury monitoring in patients scheduled to receive nephrotoxic medication and after kidney transplantation and (4) differentiation between prerenal AKI and structural kidney damage. The biomarker search and selection strategy resulted in a rational selection of an eleven-protein urinary panel for kidney injury that target these clinical needs. To assess the clinical utility of the proposed biomarker panel in kidney injury, a multiplexed LC-MS test is now in development for the intended translational research.

Prediction model for pneumonia in primary care patients with an acute respiratory tract infection: role of symptoms, signs, and biomarkers.

BACKGROUND: Diagnosing pneumonia can be challenging in general practice but is essential to distinguish from other respiratory tract infections because of treatment choice and outcome prediction. We determined predictive signs, symptoms and biomarkers for the presence of pneumonia in patients with acute respiratory tract infection in primary care. METHODS: From March 2012 until May 2016 we did a prospective observational cohort study in three radiology departments in the Leiden-The Hague area, The Netherlands. From adult patients we collected clinical characteristics and biomarkers, chest X ray results and outcome. To assess the predictive value of C-reactive protein (CRP), procalcitonin and midregional pro-adrenomedullin for pneumonia, univariate and multivariate binary logistic regression were used to determine risk factors and to develop a prediction model. RESULTS: Two hundred forty-nine patients were included of whom 30 (12%) displayed a consolidation on chest X ray. Absence of runny nose and whether or not a patient felt ill were independent predictors for pneumonia. CRP predicts pneumonia better than the other biomarkers but adding CRP to the clinical model did not improve classification (- 4%); however, CRP helped guidance of the decision which patients should be given antibiotics. CONCLUSIONS: Adding CRP measurements to a clinical model in selected patients with an acute respiratory infection does not improve prediction of pneumonia, but does help in giving guidance on which patients to treat with antibiotics. Our findings put the use of biomarkers and chest X ray in diagnosing pneumonia and for treatment decisions into some perspective for general practitioners.

Cardiospecific sevoflurane treatment quenches inflammation but does not attenuate myocardial cell damage markers: a proof-of-concept study in patients undergoing mitral valve repair.

BACKGROUND: Inflammation is considered a key mediator of complications after cardiac surgery. Sevoflurane has been shown to quench inflammation and to provide cardioprotection in preclinical studies. Clinical studies using sevoflurane confirm this effect on inflammation but do not consistently show clinical benefits. This paradox may indicate that the contribution of inflammation to postoperative sequalae is less than commonly thought or that systemic doses are too low in their local concentration. To test the latter, we evaluated the effects of intramyocardial sevoflurane delivery. METHODS: Selective myocardial sevoflurane delivery was performed during aortic cross-clamping in patients undergoing valve surgery (n=11). Results were compared with a control group not receiving sevoflurane (n=10). A reference group (n=5) was added to evaluate the effects of systemic sevoflurane delivery. Paired arterial and myocardial venous blood samples were collected at various time points post-reperfusion. Inflammatory mediators and myocardial cell damage were studied. RESULTS: Intramyocardial delivery was superior to systemic delivery in attenuation of interleukin-6 and interleukin-8 (-44% and -25%, respectively; both P=0.001). Myocardial and systemic sevoflurane delivery effectively suppressed surgery-related inflammatory responses including postoperative C-reactive protein levels when compared with controls [63 (47-99) (P=0.01) and 58 (56-81) (P=0.04) compared with 107 (79-144) mg litre(-1)]. Sevoflurane treatment did not reduce postoperative troponin T, creatine kinase, and creatine kinase-MB values. CONCLUSIONS: This proof-of-concept study suggests that intramyocardial delivery compared with the systemic delivery of sevoflurane more strongly attenuates the systemic inflammatory response after cardiopulmonary bypass without reducing postoperative markers of myocardial cell damage. CLINICAL TRIAL REGISTRATION: Nederlands Trial Register NTR2089.

The addition of the sFlt-1/PlGF ratio to the protein/creatinine ratio in multiple pregnancy: Post-hoc analysis of the PREPARE cohort study.

OBJECTIVE: To assess the predictive accuracy of the sFlt-1/PlGF ratio cut-off 38 in addition to the standard-of-care spot urine protein/creatinine ratio (PCr) for multiple pregnancies in women with suspected pre-eclampsia. STUDY DESIGN: Post-hoc analysis of a prospective cohort study. MAIN OUTCOME MEASURES: Primary outcome was the occurrence of pre-eclampsia in one and four weeks after presentation with suspected pre-eclampsia. Test characteristics with 95% confidence intervals (CI) were calculated on pre-eclampsia development in one and four weeks. RESULTS: Twenty-three multiple pregnancies with suspected pre-eclampsia between 20 and 37 weeks gestation were included for analysis. Women who eventually developed pre-eclampsia had a significantly higher PCr (34.0 vs. 16.5, p = 0.015), sFlt-1 (17033 vs. 5270 pg/ml, p = 0.047) and sFlt-1/PlGF ratio (99 vs. 25, p = 0.033) at baseline. Furthermore, PCr ≥ 30 and sFlt-1/PlGF ratio > 38 was respectively seen in 1/16 (6.3 %) and 3/16 (18.8 %) of the women who did not develop pre-eclampsia. For predicting pre-eclampsia within one week the sFlt-1/PlGF ratio sensitivity was 75.0 % [95 % CI 19.4-99.4] and the negative predictive value 93.8 % [73.0-98.8], while no pre-eclampsia developed when PCr was < 30. Consequently, the combination of these tests did not lead to an improvement in test characteristics, with non-significant differences in positive predictive value (50.0 % [29.5-70.5] versus 80.0 % [37.3-96.4]) compared to PCr alone for pre-eclampsia development in one week. CONCLUSIONS: In addition to standard-of-care spot urine PCr measurements, this study has not been able to demonstrate that the sFlt-1/PlGF ratio cut-off 38 is of added value in the prediction of pre-eclampsia in multiple pregnancy. TRIAL REGISTRATION: Netherlands Trial Register (NL8308).

High residual cardiovascular risk after lipid-lowering: prime time for Predictive, Preventive, Personalized, Participatory, and Psycho-cognitive medicine.

As time has come to translate trial results into individualized medical diagnosis and therapy, we analyzed how to minimize residual risk of cardiovascular disease (CVD) by reviewing papers on "residual cardiovascular disease risk". During this review process we found 989 papers that started off with residual CVD risk after initiating statin therapy, continued with papers on residual CVD risk after initiating therapy to increase high-density lipoprotein-cholesterol (HDL-C), followed by papers on residual CVD risk after initiating therapy to decrease triglyceride (TG) levels. Later on, papers dealing with elevated levels of lipoprotein remnants and lipoprotein(a) [Lp(a)] reported new risk factors of residual CVD risk. And as new risk factors are being discovered and new therapies are being tested, residual CVD risk will be reduced further. As we move from CVD risk reduction to improvement of patient management, a paradigm shift from a reductionistic approach towards a holistic approach is required. To that purpose, a personalized treatment dependent on the individual's CVD risk factors including lipid profile abnormalities should be configured, along the line of P5 medicine for each individual patient, i.e., with Predictive, Preventive, Personalized, Participatory, and Psycho-cognitive approaches.

Effects of sample matrix in the measurement of antithrombin by LC-MS: A role for immunocapture.

Introduction: The sample matrix composition, which is greatly affected by the type of blood collection tube used during phlebotomy, is of major importance in laboratory testing as it can influence test results. We developed an LC-MRM-MS test to molecularly characterize antithrombin in citrate plasma. The test principle differs greatly from traditional laboratory tests and the influence of varying plasma sample matrices is largely unknown. Objectives: To identify whether variations in sample matrix affect the LC-MRM-MS test for antithrombin and assess whether sample pre-processing by immunocapture reduces matrix-specific effects. Methods: Samples (n = 45) originating from four different blood collection tubes (sodium citrate, lithium heparin, K2-EDTA and K2-EDTA with protease inhibitors) were processed directly or after immunocapture. Antithrombin was digested into proteotypic peptides, which were monitored by LC-MRM-MS. Results from lithium heparin and the K2-EDTA matrices were compared to the standard sample matrix, sodium citrate, using Deming regression analysis and repeated measures one-way ANOVA. Results: Deming regression analysis of directly processed samples revealed slopes deviating >5% from the line of identity for at least six out of 22 peptides in all matrices. Significant differences between all matrices were found upon analysis by ANOVA for at least 10 peptides. Pre-processing by immunocapture led to slopes within 5% of the line of identity for nearly all peptides of the matrices. Furthermore, significant differences between matrices after immunocapture were only observed for four peptides. Conclusion: Variations in the sample matrix affect the measurement of antithrombin by LC-MRM-MS, but observed effects are greatly reduced upon pre-processing by immunocapture.

Quantifying apolipoprotein(a) in the era of proteoforms and precision medicine.

Lipoprotein(a) (Lp(a)) is an independent risk factor in the development of atherosclerotic cardiovascular diseases (ASCVD) and calcific aortic valve disease (CAVD). Lp(a) is an LDL-like particle to which apolipoprotein (a) (apo(a)) is covalently bound. Apo(a) contains a variable number of kringle IV repeats, a kringle V and a protease domain. Serum/plasma Lp(a) concentrations are traditionally expressed as total particle mass in mg/L. Concern has arisen lately as flawed Lp(a) mass tests have masked its clinical utility. The determinants of variability in Lp(a) composition were investigated, including the apo(a) size polymorphism, post-translational modifications -N- and O-glycosylation- and the lipid:protein ratio. Depending on the number of kringle IV-2 repeats, the theoretical protein content of the Lp(a) particle varies between 30 and 46 (w/w) %, which inescapably confounds Lp(a) mass measurements. The authors advocate that reporting of Lp(a) particle concentrations in mass units is metrologically inappropriate and should be abandoned, as it results in systematically biased Lp(a) results. Enabling technology, such as mass spectrometry, allows unequivocal molecular characterization of the apo(a) measurand(s) and accurate quantitation of apo(a) in molar units, unaffected by apo(a) size polymorphism. To guarantee that Lp(a)/apo(a) tests are fit-for-clinical-purpose, basic metrology principles should be implemented upfront during test development.

Fresh frozen plasma transfusion for reversal of prolonged post-anaesthesia apnoea.

An 18-year old woman admitted for tonsillectomy developed prolonged post-operative paralysis after anaesthesia with mivacurium. Investigation revealed a decreased cholinesterase activity because of a homozygous atypical and heterozygous K variant of the cholinesterase gene. Transfusion of fresh frozen plasma was associated with reversal of the respiratory paralysis and complete recovery.

[Anejaculation caused by haemosiderosis: male infertility in hereditary haemochromatosis]. / Zaadloos door ijzerstapeling: mannelijke infertiliteit bij hereditaire hemochromatose.

A couple was investigated for subfertility. Haemochromatosis was suspected when the 36-year-old man had failure of ejaculation, fatigue and limited facial hair growth. Haemochromatosis was confirmed by an iron saturation of 102% (normal range: 20-45), a highly elevated serum ferritin concentration of 5468 mg/1l (normal range: 18-280) and highly elevated liver enzymes. Molecular genetics showed homozygous C282Y mutation of the HFE gene. Due to consequent venesection therapy, levels of ferritin and transferrin decreased and liver enzymes normalized. However luteinizing hormone and follicle stimulating hormone failed to increase to normal levels. Treatment with gonadotropins was then applied, which corrected ejaculation and semen characteristics. His partner failed to become pregnant with ovulation stimulation and intrauterine inseminations. After two unsuccessful IVF procedures she became pregnant in the third procedure. Haemochromatosis should be considered and iron studies performed if subfertility due to an endocrine disorder is being investigated. Deposition in the pituitary or the gonads of the HFE-mutated patients leads to hypogonadism. Most of the patients with C282Y mutation are homozygous (85-90%), but the majority of the carriers will not develop the disease. Deficiency of hepcidin, an important regulator for the iron metabolism, was suspected in our patient, based on the early onset of his disease and the low serum levels of hepcidin. The age at diagnosis and the start of venesections is critical for reversal of organ damage. Aggressive venesection can restore hypothalamic-pituitary-gonadal function, preventing further organ damage. But with increasing disease progression venesection will not restore azoospermia or the failure to ejaculate.

Modulation of lipoprotein(a) atherogenicity by high density lipoprotein cholesterol levels in middle-aged men with symptomatic coronary artery disease and normal to moderately elevated serum cholesterol. Regression Growth Evaluation Statin Study (REGRESS) Study Group.

OBJECTIVES: This study sought to examine whether lipoprotein(a) levels predict coronary artery lumen changes in patients with symptomatic coronary artery disease (CAD) and normal to moderate hypercholesterolemia. BACKGROUND: Recent conflicting reports have confirmed or refuted the association of lipoprotein(a) with clinical events or angiographically verified disease progression. METHODS: The association between serum lipoprotein(a) and changes in coronary artery lumen was studied in 704 men entered into the Regression Growth Evaluation Statin Study (REGRESS), a double-blind, placebo-controlled, quantitative angiographic study that assessed the effect of 2 years of pravastatin treatment. The primary end points were changes in average mean segment diameter (MSD) and average minimal obstruction diameter (MOD). Pravastatin- and placebo-treated patients were classified as having progressing, regressing or stable CAD, and median lipoprotein(a) concentrations were compared. Bivariate and multivariate regression analyses were performed in the overall patient group and in high risk subgroups. RESULTS: Pravastatin treatment did not affect serum apolipoprotein(a) levels. Median in-trial (sampled at 24 months) apolipoprotein(a) levels for regressing, stable and progressing CAD were, respectively, 130, 162 and 251 U/liter in placebo-treated patients and 143, 224 and 306 U/liter in pravastatin-treated patients. Predictors of MSD and MOD changes were baseline MSD and MOD, in-trial apolipoprotein(a), in-trial high density lipoprotein (HDL) cholesterol and baseline use of long-acting nitrates. The multivariate models predicted 14% of MSD changes and 12% of MOD changes; apolipoprotein(a) predicted only 2.6% and 4.8%, respectively. However, in patients with in-trial HDL cholesterol levels <0.7 mmol/liter, apolipoprotein(a) predicted up to 37% of the arteriographic changes. CONCLUSIONS: Serum lipoprotein(a) levels predict coronary artery lumen changes in normal to moderately hypercholesterolemic white men with CAD; its atherogenicity is marked in the presence of concomitant hypoalphalipoproteinemia.

Detection of coronary artery reperfusion with creatine kinase-MB determinations during thrombolytic therapy: correlation with acute angiography.

Increases in plasma creatine kinase-MB (MB CK) were correlated with the onset of coronary artery reperfusion determined angiographically in 32 patients with acute myocardial infarction who were treated with recombinant human tissue-type plasminogen activator (rt-PA). Reperfusion occurred in 14 (70%) of 20 patients with left anterior descending coronary artery occlusion and in 8 (73%) of 11 patients with right coronary artery occlusion. One patient had persistent left circumflex coronary artery occlusion. Plasma MB CK levels (radioimmunometric assay) did not increase significantly in patients with persistent occlusion, but increased by a mean (+/- SEM) of 8 +/- 1 and 6 +/- 1 times over pretreatment levels at the end of the infusion in patients with a reperfused left anterior descending and right coronary artery, respectively. When a greater than or equal to 2.5-fold increase in MB CK levels at the end of the rt-PA infusion was taken as evidence of reperfusion of the left anterior descending coronary artery, 13 (93%) of 14 patients with reperfusion and 5 (83%) of 6 with persistent occlusion were correctly identified. When a greater than or equal to 2.2-fold increase in MB CK levels was used to identify right coronary artery reperfusion, seven (89%) of eight patients with persistent occlusion were correctly identified. The sensitivity and specificity of these indexes, derived from and applied to the same patient group, were 91 and 89%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Thrombolysis-induced coronary reperfusion causes acute and massive interstitial release of cardiac muscle cell proteins.

OBJECTIVE: Reperfusion of the infarct-related artery in patients with acute myocardial infarction limits infarct size, but also causes accelerated release into plasma of cardiac tissue proteins. The latter effect could reflect either enhanced protein washout from the heart or abrupt disruption of myocyte membranes. The present study indicates that the latter mechanism prevails. METHODS: In 26 patients, patency of the infarct-related artery was determined by coronary angiography 90 min and 5-7 days after thrombolytic treatment. Continuous electrocardiography was performed during the first 24 h after admission. Cumulative release of myoglobin (Mb) and creatine kinase (CK) into plasma was calculated from frequently sampled plasma concentrations. RESULTS: In patients with a patent infarct-related artery after 90 min, onset of a rapid (> 50%) decrease in ST-vector magnitude coincided with an equally rapid increase in QRS-vector magnitude, and with a sudden onset of release into plasma of Mb as well as CK. In these patients, a maximal initial release rate was observed and cumulative release conformed closely to a simple model for sudden interstitial liberation of proteins. In contrast, protein release started more gradually and could not be fitted to this model, in patients with persistent occlusion of the infarct-related artery at 90 min and absence of ST-vector normalisation. CONCLUSIONS: Previous studies have demonstrated significant myocardial salvage by timely reperfusion therapy. Nevertheless, this study indicates that the moment of recanalisation of the infarct-related artery coincides with sudden and massive disruption of myocyte membranes. Attenuation of this effect, if possible, could further improve the benefits of reperfusion therapy.

Hypothalamic-pituitary-adrenal axis functioning in Huntington's disease and its association with depressive symptoms and suicidality.

Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis has been reported in Huntington's disease (HD). In non-HD populations, alterations in HPA axis activity have been associated with depression and suicidality. The present study aims to compare HPA axis activity between HD mutation carriers and controls, and examine its association with depressive symptoms and suicidality. To this end, salivary cortisol concentrations at seven time points, as well as depressive symptoms and suicidality, were assessed in 49 pre-motor, 102 motor symptomatic mutation carriers and 55 controls, at baseline and follow-up combined. Differences in parameters of HPA axis activity between these three groups, and their associations with depressive symptoms and suicidality in HD mutation carriers, were analysed using multilevel regression analyses. There were no differences in parameters of HPA axis activity between mutation carriers and controls, whereas pre-motor symptomatic mutation carriers had a significantly higher area under the curve to the increase (AUCi ) compared to motor symptomatic mutation carriers. In the entire HD cohort, HPA axis activity was not associated with depressive symptoms or suicidality. After stratifying mutation carriers into pre-motor, early and advanced disease stages, ß values differed between these groups. Remarkably, a higher AUCi was significantly associated with depressive symptoms in pre-motor and early disease stage mutation carriers, with a reverse nonsignificant association in advanced disease stage mutation carriers. The lower AUCi in motor symptomatic mutation carriers and the varying associations with depressive symptoms and suicidality in pre-motor, early and advanced disease stages could possibly be explained by exhaustion of the HPA axis after prolonged stress-induced HPA axis hyperactivity and deserves further longitudinal study.

Human longevity is characterised by high thyroid stimulating hormone secretion without altered energy metabolism.

Few studies have included subjects with the propensity to reach old age in good health, with the aim to disentangle mechanisms contributing to staying healthier for longer. The hypothalamic-pituitary-thyroid (HPT) axis maintains circulating levels of thyroid stimulating hormone (TSH) and thyroid hormone (TH) in an inverse relationship. Greater longevity has been associated with higher TSH and lower TH levels, but mechanisms underlying TSH/TH differences and longevity remain unknown. The HPT axis plays a pivotal role in growth, development and energy metabolism. We report that offspring of nonagenarians with at least one nonagenarian sibling have increased TSH secretion but similar bioactivity of TSH and similar TH levels compared to controls. Healthy offspring and spousal controls had similar resting metabolic rate and core body temperature. We propose that pleiotropic effects of the HPT axis may favour longevity without altering energy metabolism.

Serum lipid and apolipoprotein levels in a Nigerian population sample.

Serum lipids and apoproteins have been measured in 307 men and 235 women living around Benin City in Nigeria. Total serum cholesterol values are low compared both to White Western populations and to American Blacks. HDL-cholesterol levels, however, are comparable to values in Western and Oriental men, but lower than in Western women. A highly significant correlation exists between total cholesterol and apo B and between HDL-cholesterol and apo A-I in men and women. The low serum lipid values are related to a low dietary fat intake, almost exclusively from palm oil, in the Nigerian population.

Long-term prognostic value of serial troponin T bedside tests in patients with acute coronary syndromes.

The early presence of troponin T in serum strongly predicts short-term mortality and myocardial infarction in patients with acute coronary syndromes. We investigated the long-term outcome of the prognostic significance of the troponin T rapid bedside assay (TROPT) and compared this with the quantitative troponin T assay (cTnT enzyme-linked immunosorbent assay), myoglobin and creatine kinase-MB (CK-MB) mass. One hundred sixty-three patients with chest pain and suspected acute coronary syndromes were studied and followed prospectively for 3 years. Serial blood specimens were obtained at admission and at 3, 6, 12, 24, 48, 72, and 96 hours after admission. Patients were classified as having acute myocardial infarction in 99 patients (61%), unstable angina in 34 patients (21%), and no evidence for acute cardiac ischemia in 30 patients (18%). At 3 years, 28 patients (17%) had died of which 25 deaths (15%) were for cardiac reasons. Twenty-one patients (13%) had a nonfatal (recurrent) myocardial infarction. At admission 29% of the patients were TROPT positive (> or = 0.2 microg/L), another 31% became positive within 12 hours, and 39% remained negative. When adjusted for baseline variables, a positive TROPT (any sample 0 to 12 hours) was independently associated with a higher risk of cardiac mortality (RR 4.3, 95% confidence interval [CI] 1.3 to 14.0). Because troponin T stays elevated up to 2 weeks, later TROPT results between 24 and 96 hours remained significantly predictive for mortality. The cTnT enzyme-linked immunosorbent assay (any sample 0 to 12 hours; cutoff > or = 0.2 microg/L) was similarly predictive (RR 2.9, 95% CI 1.0 to 8.6). Early myoglobin results were significantly prognostic for cardiac mortality up to 12 hours after admission (RR 3.7; 95% CI 1.0 to 12.0). In contrast, serial CK-MB mass measurements were not predictive of mortality. Thus, a combination of a baseline TROPT and an additional TROPT 12 hours or later identifies a subgroup of patients at high risk for subsequent mortality and reinfarction, both at short-term but also at long-term.

Noninvasive assessment of reperfusion and reocclusion after thrombolysis in acute myocardial infarction.

The clinical significance of ST-segment changes and of the time course of appearance in serum of different cardiac proteins has been reviewed for the diagnosis of coronary reperfusion and reocclusion after thrombolysis. In particular, the value of serial 12-lead electrocardiographic (ECG) studies, of Holter monitoring, and of continuous multilead computer-assisted ECG monitoring is compared. Regarding the serum proteins, the clinical significance of reperfusion indices described so far for serum creatine kinase (CK), its isoenzyme serum creatinine kinase MB, the CK isoforms, and myoglobin is reviewed. Emphasis is placed on (1) the calculation method used for deriving the reperfusion indices; (2) the sensitivity and the specificity of the reperfusion indices; (3) the minimum turn-around time needed to produce the reperfusion indices (depending on the practicability of the analytical and calculation methods and their applicability in an emergency laboratory); (4) the ability of the indices to produce reliable estimates of reperfusion efficacy of the thrombolytic agents under study; and (5) the ability of the marker proteins to detect reinfarction as well as the suitability of the markers to detect real-time necrosis.

Coronary recanalization rate after intravenous bolus of alteplase in acute myocardial infarction.

The demonstration in animals that recombinant tissue-type plasminogen activator produces prolonged thrombolysis after its clearance from the circulation has prompted a few pilot studies of bolus administration in patients. Alteplase (bolus dose of 70 mg) resulted in the highest recanalization rate in our previous pilot study comparing bolus doses of 50, 60 and 70 mg of alteplase in patients with acute myocardial infarction. The aim of the present trial was to assess the efficacy and safety of the same bolus dose in a larger number of patients. A further objective was to study the angiographic reocclusion rate at 12 to 24 hours in patients who had a recanalized infarct-related coronary artery at 90 minutes and were randomized at that time to a bolus dose or an infusion for 3 hours of 30 mg of alteplase. Sixty patients with acute myocardial infarction and angiographically documented total occlusion of the infarct-related coronary artery before thrombolysis were treated within 5 hours of onset of symptoms with an intravenous 70-mg bolus dose of alteplase (or 80 mg if body weight was greater than or equal to 90 kg). Each patient received 5,000 IU of heparin intraarterially and 100 mg of aspirin by mouth before administration of alteplase. Coronary angiography was repeated 60 and 90 minutes after alteplase administration. The recanalization rate of the infarct-related coronary artery was 55% (95% confidence interval, 43 to 66%) at 60 minutes and 48% (95% confidence interval, 37 to 60%) at 90 minutes. Pretreatment levels of lipoprotein (a) were not significantly related to recanalization.(ABSTRACT TRUNCATED AT 250 WORDS)