Abstract
Background
The CARdiac MARker Guideline Uptake in Europe (CAMARGUE) program is a multi-country audit of the use of cardiac biomarkers in routine clinical practice.
Methods
An email link to a ...web-based questionnaire of 30 multiple-choice questions was distributed via the professional societies in Europe.
Results
374 questionnaires were returned from 39 countries, the majority of which were in northern Europe with a response rate of 8.2%–42.0%. The majority of the respondents were from hospitals with proportionately more responses from central hospitals than district hospitals. Cardiac troponin was the preferred cardiac biomarker, evenly split between cardiac troponin T (cTnT) and cardiac troponin I (cTnI). Aspartate transaminase and lactate dehydrogenase are no longer offered as cardiac biomarkers. Creatine kinase, creatine kinase MB isoenzyme, and myoglobin continue to be offered as part of the cardiac biomarker profile in approximately on 50% of respondents. There is widespread utilization of high sensitivity (hs) troponin assays. The majority of cTnT users measure hs-cTnT. 29.5% of laboratories measure cTnI by a non-hs method but there has been substantial conversion to hs-cTnI. The majority of respondents used ng/L and use the 99th percentile as the upper reference limit (71.9% of respondents). A range of diagnostic protocols are in use.
Conclusions
There is widespread utilization of hs troponin methods. A significant minority do not use the 99th percentile as recommended and there is, as yet, little uptake of very rapid diagnostic strategies. Education of laboratory professionals and clinicians remains a priority.
The European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) initiated the CArdiac MARker Guidelines Uptake in Europe (CAMARGUE) Study to survey if current biomarker testing for heart ...failure (HF) in Europe is in accordance with up-dated guidelines.
A web-based questionnaire was distributed to clinical laboratories via European biochemical societies in 2019. Questions covered the type of natriuretic peptide (NP) assays performed, decision limits for HF, and opinion concerning requirement of different thresholds in patients with renal failure or obesity.
There were 347 participating laboratories mostly from European countries with 266 offering NP testing. NP testing was increased from 67% to 77% between 2013 and 2019. NT-proBNP remained the preferred biomarker. Recommended decision limits were implemented for BNP (85%) and better focused for NT-proBNP (40%) than in the previous survey. The survey revealed that laboratorians are willing to support the translation of adjusted cut-off values for age, gender and for patients with conditions like renal insufficiency.
Guidelines stimulate clinical laboratories to offer NP testing with high value for the diagnosis and management of HF, and to present adjusted medical decision limits. Future guidelines should encourage the use of personalized cut-offs for some confounding factors.
Although laboratory medicine practise varies across the European Union’s (EU) member states, the extent of overlap in scope is such that a common syllabus describing the education and training ...associated with high-quality, specialist practise can be identified. In turn, such a syllabus can help define the common set of skills, knowledge and competence in a Common Training Framework (CTF) for non-medical Specialists in Laboratory Medicine under EU Directive 2013/55/EU (The recognition of Professional Qualifications). In meeting the requirements of the directive’s CTF patient safety is particularly enhanced when specialists seek to capitalise on opportunities for free professional migration across EU borders. In updating the fourth syllabus, the fifth expands on individual discipline requirements, new analytical techniques and use of statistics. An outline structure for a training programme is proposed together with expected responsibilities of trainees and trainers; reference is provided to a trainee’s log book. In updating the syllabus, it continues to support national programmes and the aims of EU Directive 2013/55/EU in providing safeguards to professional mobility across European borders at a time when the demand for highly qualified professionals is increasing in the face of a disparity in their distribution across Europe. In support of achieving a CTF, the syllabus represents EFLM’s position statement for the education and training that underpins the framework.
Abstract Background Despite international standardization programs for LDLc and HDLc measurements, results vary significantly with methods from different manufacturers. We aimed to simulate the ...impact of analytical error and hypertriglyceridemia on HDLc- and LDLc-based cardiovascular risk classification. Methods From the Dutch National EQA-2012 external quality assessment of 200 clinical laboratories, we examined data from normotriglyceridemic (∼1 mmol/l) and hypertriglyceridemic (∼7 mmol/l) serum pools with lipid target values assigned by the Lipid Reference Laboratory in Rotterdam. HDLc and LDLc were measured using direct methods of Abbott, Beckman, Siemens, Roche, Olympus, or Ortho Clinical Diagnostics. We simulated risk reclassification using HDL- and sex-specific SCORE multipliers considering two fictitious moderate-risk patients with initial SCORE 4% (man) and 3% (woman). Classification into high-risk treatment groups (LDLc >2.50 mmol/l) was compared between calculated LDLc and direct LDLc methods. Results Overall HDLc measurements in hypertriglyceridemic serum showed negative mean bias of −15%. HDL-multipliers falsely reclassified 70% of women and 43% of men to a high-risk (SCORE >5%) in hypertriglyceridemic serum ( P < 0.0001 vs. normotriglyceridemic serum) with method-dependent risk reclassifications. Direct LDLc in hypertriglyceridemic serum showed positive mean bias with Abbott (+16%) and Beckman (+14%) and negative mean bias with Roche (−7%). In hypertriglyceridemic serum, 57% of direct LDLc measurements were above high-risk treatment goal (2.50 mmol/l) vs. 29% of direct LDLc (33% of calculated LDLc) in normotriglyceridemic sera. Conclusion LDLc and HDLc measurements are unreliable in severe hypertriglyceridemia, and should be applied with caution in SCORE risk classification and therapeutic strategies.
Correct information provided by guidelines may reduce laboratory test related errors during the pre-analytical, analytical and post-analytical phase and increase the quality of laboratory results.
...Twelve clinical practice guidelines were reviewed regarding inclusion of important laboratory investigations. Based on the results and the authors’ experience, two checklists were developed: one comprehensive list including topics that authors of guidelines may consider and one consisting of minimal standards that should be covered for all laboratory tests recommended in clinical practice guidelines. The number of topics addressed by the guidelines was related to involvement of laboratory medicine specialists in the guideline development process.
The comprehensive list suggests 33 pre- analytical, 37 analytical and 10 post-analytical items. The mean percentage of topics dealt with by the guidelines was 33% (median 30%, range 17%–55%) and inclusion of a laboratory medicine specialist in the guideline committee significantly increased the number of topics addressed. Information about patient status, biological and analytical interferences and sample handling were scarce in most guidelines even if the inclusion of a laboratory medicine specialist in the development process seemingly led to increased focus on, e.g., sample type, sample handling and analytical variation. Examples underlining the importance of including laboratory items are given.
Inclusion of laboratory medicine specialist in the guideline development process may increase the focus on important laboratory related items even if this information is usually limited. Two checklists are suggested to help guideline developers to cover all important topics related to laboratory testing.
OBJECTIVES
The objective of this prospective study was to evaluate the relation between high lipoprotein(a) levels and thrombotic and restenotic events after coronary stent implantation.
BACKGROUND
...Lipoprotein(a) may promote atherogenesis, coronary thrombosis and restenosis after balloon angioplasty, but the clinical significance remains unclear.
METHODS
The study included 2,223 consecutive patients with successful coronary stent placement. According to the serum level of lipoprotein(a), patients were divided in two groups: 457 patients of the highest quintile formed the high lipoprotein(a) group, and 1,766 patients of the lower four quintiles formed the low lipoprotein(a) group. Primary end points were the incidence of angiographic restenosis at six months and the event-free survival at one year. Secondary end point was the incidence of angiographic stent occlusion.
RESULTS
Early stent occlusion occurred in four of the 457 patients (0.9%) with high and 37 of the 1,766 patients (2.1%) with low lipoprotein(a) levels, odds ratio of 0.41 (95% confidence interval, 0.15 to 1.16). Angiographic restenosis occurred in 173 of the 523 lesions (33.2%) in the high lipoprotein(a) group and 636 of the 1,943 lesions (32.7%) in the low lipoprotein(a) group, odds ratio of 1.02 (0.83 to 1.25). The probability of event-free survival was 73.0% in the high lipoprotein(a) group and 74.8% in the low lipoprotein(a) group (p = 0.45). On the basis of the findings in the low lipoprotein(a) group, the power of this study to detect a 25% increase in the incidence of restenosis and adverse events in the group with elevated lipoprotein(a) was 90% and 75%, respectively.
CONCLUSIONS
Elevated lipoprotein(a) levels did not influence the one-year clinical and angiographic outcome after stent placement. Thrombotic events and measures of restenosis were not adversely affected by the presence of high lipoprotein(a) levels.
Aims
N‐terminal pro brain natriuretic peptide (NT‐proBNP) is a potent marker of heart failure and other cardiac diseases. The value of NT‐proBNP testing in the medical emergency department (ED) was ...assessed in patients >65 years old.
Methods and results
This large, prospective, randomized, controlled, multicentre trial was conducted in six medical EDs. Data for evaluation of the primary endpoint of hospitalization were available for 1086 patients. Median NT‐proBNP was 582 pg/mL. A total of 16% of patients presented with NT‐proBNP <150 pg/mL (low), 55% with NT‐proBNP between 150 and 1800 pg/mL (intermediate), and 29% with NT‐proBNP >1800 pg/mL (high). NT‐proBNP was positively correlated with hospital admission odds ratio (OR) for high vs. low 2.9, P < 0.0001, length of stay (8.5 days vs. 3.5 days for high vs. low, P < 0.01), in‐hospital death (3.9% vs. 0% for high vs. low, P < 0.01), 6 months re‐hospitalization (OR for high vs. low 5.1, P < 0.0001), and 6 months death or re‐hospitalization (OR for high vs. low 5.7, P < 0.0001). Knowledge of NT‐proBNP had no significant effect on the primary endpoint hospital admission and the secondary endpoints intermediate/intensive care unit (IMC/ICU) admission, length of stay, re‐hospitalization and death, or re‐hospitalization in the total cohort. However, patients with high open NT‐proBNP (>1800 pg/mL) were more likely to be admitted to the hospital (P < 0.05) and IMC/ICU (P < 0.05), whereas patients with low open NT‐proBNP (<150 pg/mL) were less likely to be admitted (P < 0.05) compared with patients with blinded NT‐proBNP.
Conclusion
Although NT‐proBNP does not affect overall hospitalization, it is associated with better stratification of patient care and is strongly correlated with subsequent utilization of hospital resources and prognosis.
We hypothesized that a higher degree of inflammatory response to coronary stenting, as measured by the change in C-reactive protein (CRP) levels after intervention in patients with stable or unstable ...angina, would be related to a higher risk of in-stent restenosis.
We studied 1800 consecutive patients with stable or unstable angina treated with coronary stenting. C-reactive protein levels were serially measured before and after the intervention. The difference (Δ) between highest CRP values after intervention and CRP values before intervention was calculated. Patients were grouped into tertiles according to ΔCRP values. The primary end point was angiographic restenosis (diameter stenosis ≥50% at 6-month angiography). The secondary end point was clinical restenosis, defined as target vessel revascularization performed in the presence of angiographic restenosis and symptoms or signs of ischemia.
No relationship was found between CRP values at baseline and angiographic restenosis (
P = .88). On the other hand, the change between baseline and peak postintervention CRP values strongly correlated with angiographic restenosis (30.5% in the upper tertile with ΔCRP values >11.8 mg/L, 25.3% in the middle tertile with ΔCRP values 3.0-11.8 mg/L, and 21.5% in the lower tertile with ΔCRP values <3.0 mg/L,
P = .002) as well as with clinical restenosis (
P = .01). Patients in the upper tertile had the highest risk of restenosis even after adjustment for other covariates.
The inflammatory response to coronary stenting as assessed by the change in CRP correlates with the development of in-stent restenosis. These findings provide strong support for the role of inflammation in restenosis.
Cardiac troponins T (cTnT) and I (cTnI) are the most sensitive biochemical parameters in the detection of myocardial damage. In neonates, in utero exposure to tocolytic therapy results in detectable ...values of cardiac troponins after delivery. Additionally, some preliminary results suggest that the upper reference limits for healthy newborns are higher than those for adults but definitive reference limits for newborns are not available. Our objective was to determine those limits.
In this study we investigated the distribution of cTnT and cTnI in cord blood of 869 healthy newborns. cTnT was determined with the 3rd generation assay and cTnI with the Dade Behring assay on a Dimension RxL. For data analysis Student's
t test and the Mann–Whitney
U test were used.
Using the 99th percentile, the upper reference limit in healthy termed newborns was 0.097 μg/l for cTnT and 0.183 μg/l for cTnI. Compared to the adult values, the newborn upper limit was tripled for cTnT and doubled for cTnI. Statistically significant differences were found between males and females for cTnT and between natural childbirth and caesarean section for cTnI.
Healthy-termed newborns have a higher upper reference limit for both cTnT and cTnI compared to adults. This circumstance must be taken into account when interpreting slightly “elevated” cTnT and cTnI values in newborns.
To investigate the prognostic value of elevated C-reactive protein levels in patients with stable angina who underwent coronary stenting.
We followed a consecutive series of 1152 patients with stable ...angina who had undergone coronary stenting. We measured baseline C-reactive protein levels before stenting with a high-sensitivity assay; 651 patients (57%) had elevated C-reactive protein levels (>5 mg/L). The primary endpoint was either death or myocardial infarction within 1 year after the procedure. Angiographic restenosis was defined as a ≥50% diameter stenosis at follow-up angiography.
During the 1-year follow-up, 62 (9.5%) of the 651 patients with an elevated C-reactive protein level and 24 (4.8%) of the 501 patients with normal levels died or had a myocardial infarction (
P = 0.002). In a multivariate analysis, elevated baseline C-reactive protein levels were associated with almost a twofold increase in the rate of death or myocardial infarction after coronary stenting (hazard ratio = 1.8; 95% confidence interval: 1.1 to 2.9). Most of the difference in the event rates developed within the first 30 days. Baseline C-reactive protein levels did not correlate with restenosis.
Elevated preprocedural C-reactive protein levels are associated with a less favorable prognosis in patients with stable angina who undergo coronary stenting. The measurement of C-reactive protein levels in these patients may help to identify those who may benefit from a treatment strategy aimed at the attenuation of inflammation.
PDF
