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Natriuretic peptides (NP) play an essential role in heart failure (HF) regulation, and their measurement has improved diagnostic and prognostic accuracy. Clinical symptoms and objective measurements, such as NP levels, should be included in the HF definition to render it more reliable and consistent among observers, hospitals, and healthcare systems. BNP and NT-proBNP are reasonable surrogates for cardiac disease, and their measurement is critical to early diagnosis and risk stratification of HF patients. NPs should be measured in all patients presenting with dyspnea or other symptoms suggestive of HF to facilitate early diagnosis and risk stratification. Both BNP and NT-proBNP are currently used for guided HF management and display comparable diagnostic and prognostic accuracy. Standardized cutoffs for each NP assay are essential for data comparison. The value of NP testing is recognized at various levels, including patient empowerment and education, analytical and operational issues, clinical HF management, and cost-effectiveness.

Background: Measurement of cardiac troponin (cTn) by a high sensitivity method is now the recommended strategy for the detection of myocardial injury. An international survey was undertaken to assess how this has been implemented., Methods: A questionnaire based around 14 domains on cardiac biomarkers was distributed electronically with the aid of professional societies accessed by a web link within the invitation. Results were returned electronically then extracted into a relational database for analysis., Results: Responses were obtained from 663 laboratories across 76 countries ranging from 1 to 69 largest country. The majority of responses (79.6%) came from the European area. Responses were grouped into broad geographic areas for analysis. Most responses came from hospitals providing a local and regional service of which the majority provided angioplasty. cTn measurement was the dominant biomarker. The majority of laboratories include creatine kinase (CK) in their cardiac profile and approximately 50% also offer the MB isoenzyme of CK. The majority of laboratories (91.9%) measure cTn by a high sensitivity method. Sex specific reference ranges were typically implemented for cardiac troponin I but not for cardiac troponin T. The preferred unit of measurement was nanograms/L. A structured decision-making pathway utilising high sensitivity cTn measurement was used by 83.3% of laboratories who responded. Single sample rule out is common but the majority used serial sampling strategy based on measurement on admission and three hours., Conclusions: Measurement of cTn by a high sensitivity method is now well established internationally, the use of rapid diagnostic protocols lags behind., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [POC: Honoria Siemens Healthineers, Abbott Laboratories; Advisory Boards Radiometer, Psyros diagnostics, LumiraRx, Siemens Healthineers; Consultant to IFCC Committee on Clinical Applications of Cardiac Bio-Markers (C-CB). AHL: Honoraria Siemens Healthineers, Abbott Laboratories; Research support from Abbott Laboratories, Beckman Coulter and Siemens Healthineers. KA: Research Grants Siemens Healthineers, Roche Diagnostics; Consultancy CardiNor; Honoraria Siemens Healthineers, SNIBE; Advisory Boards Roche Diagnostics, Siemens Healthineers, SpinChip; Associate Editor Clinical Biochemistry, Chair International Federation of Clinical Chemistry Committee on Clinical Application of Cardiac Bio-Markers. DG: None. JS: None. KP: None. SS: Honoria Roche Diagnostics, Abbott Laboratories, SNIBE; President Serbian Society for Clinical Laboratory and Science (SCLM). HB: Grants Roche Diagnostics, Beckman Coulter. MTHL Clinical Research Training Fellowships (MR/W000598/1) from the Medical Research Council. NLM Chair Award (CH/F/21/90010), Programme Grant (RG/20/10/34966) and a Research Excellence Award (RE/18/5/34216) from the British Heart Foundation; Honoraria Abbott Laboratories, Siemens Healthineers, Roche Diagnostics; Advisory Boards Psyros Diagnostics, Roche Diagnostics, LumiraDx; Research Support Siemens Healthineers. PL. Chair Science Committee LabQuality Days.]., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: 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., Methods: 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., Results: 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., Conclusion: 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., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The aim of this survey was to investigate how well heart failure (HF) guidelines for use of natriuretic peptides (NPs) have been implemented in laboratory practice in Europe and North America., Methods: In 2013 and 2014, a web-based questionnaire was distributed via North American and European biochemical societies. Questions covered assay performed, reason for method choice, decision limits for HF, and laboratory accreditation status., Results: There were 442 European Union and 91 North American participating laboratories with response rates of 50% and 64% from major or university hospitals, respectively. NP measurements were offered in 67% of European Union and 58% of North American respondents. N-terminal pro-B-type natriuretic peptide (NT-proBNP) was most widely used in Europe (68%) and B-type natriuretic peptide (BNP) was more commonly used (58%) in North America. The most frequent reason for use of a specific assay was the availability of instruments that measure either NT-proBNP (51%) or BNP (67%). For diagnosis of acute HF, NT-proBNP decision limits were diverse; age-dependent limits based on the 2012 European Society of Cardiology (ESC) recommendations were used in only 17% of European sites and 26% of North American sites. For BNP, the guideline-recommended acute HF decision limit of 100 ng/L was better adhered to in Europe (48%) and North America (57%). Surprisingly, similar decision limits were stated for acute and chronic HF by >50% of respondents., Conclusions: NP measurement for HF diagnosis was available in >50% of responding laboratories. However, guideline recommended cutoff values for both acute and chronic HF were still implemented in <30% of participating medical centers., (© 2016 American Association for Clinical Chemistry.)

Background: We undertook an assessment of current use of evidence-based guidelines for the use of cardiac biomarkers in Europe (EU) and North America (NA)., Methods: In 2013-2014 a web-based questionnaire was distributed via NA and EU biochemical societies. Questions covered cardiac biomarkers measured, analytical methods used, decision thresholds, and use of decision-making protocols. Results were collated using a central database and analyzed using comparative and descriptive nonparametric statistics., Results: In EU, returns were obtained from 442 hospitals, 50% central or university hospitals, and 39% from local hospitals from 35 countries with 395/442 (89%) provided an acute service. In NA there were 91 responses (63.7% central or university hospitals, 19.8% community hospitals) with 76/91 (83.5%) providing an acute service. Cardiac troponin was the preferred cardiac biomarker in 99.5% (EU) and 98.7% (NA), and the first line marker in 97.7% (EU) and 97.4% (NA). There were important differences in the choice of decision limits and their derivations. The origin of the information was also significantly different, with EU vs NA as follows: package insert, 61.9% vs 40%; publications, 17.1% vs 15.0%; local clinical or analytical validation choice, 21.0% vs 45.0%; P = 0.0003., Conclusions: There are significant differences between EU and NA use of cardiac biomarkers. This probably relates to different availability of assays between EU and NA (such as high-sensitivity troponin assays) and different laboratory practices on assay introduction (greater local evaluation of assay performance occurred in NA)., (© 2016 American Association for Clinical Chemistry.)

Objective: To evaluate the efficacy of first trimester combined screening for Down's syndrome in Northern Finland during the first 10 years of practice., Methods: During 1 January 2002 to 31 December 2011, 47,896 women participated voluntarily in combined screening during first trimester. The risk cutoff was 1:250. The study period was divided into two time periods; 2002-2006 and 2007-2011., Results: During the first half of the study period, the detection rate (DR) was 77.3% with a 4.9% false-positive rate (FPR). During the latter half, the DR was 77.1% with a 2.8% FPR., Conclusions: An important issue is the number of invasive procedures needed to detect one case of Down's syndrome. The screening performance improved markedly in the latter five years period since the FPR lowered from 4.9% to 2.8% and the number of invasive procedures needed to detect one case of Down's syndrome lowered from 15 to 11.

Objective: To compare the efficacy of fetal nuchal translucency screening, maternal serum screening and combined screening for Down syndrome., Design: A prospective study., Setting: University hospital and its public health care district in Northern Finland., Population: A total of 35,314 women participated in the first-trimester screening for Down syndrome within the public healthcare system in 2002-08. There were 95 pregnancies involving Down syndrome. Serum samples were obtained from 35,314 women, nuchal translucency was measured in 27,144 pregnancies and full combined screening was performed in those pregnancies, including 76 involving Down syndrome., Methods: The adjusted estimated risk for Down syndrome was calculated using the Perkin Elmer AutoDELFIA® time-resolved fluoroimmunoassay kit for the measurement of pregnancy-associated plasma protein-A and free β-human chorionic gonadotropin. Nuchal translucency was measured by trained personnel in a university or district hospital. Risk cut-off figures 1:250 and 1:300 at term were used., Main Outcome Measures: Differences in detection rate, false-positive rate, positive and negative predictive values between nuchal translucency screening, serum screening and combined screening., Results: Using the risk cut-off figure 1:250, the detection rates for serum screening, nuchal translucency screening and combined screening were 64.2, 64.5 and 72.4%, respectively and the false-positive rates were 7.8, 4.4 and 4.0%, respectively., Conclusions: Combined screening is the method of choice for Down syndrome screening in Finland., (© 2013 Nordic Federation of Societies of Obstetrics and Gynecology.)

Objectives: We evaluated the performance of first trimester screening for Down syndrome in women less than 35 years of age (study group) and in women aged 35 years or more (control group) in an unselected low-risk population., Methods: The study group comprised a total of 63,945 women who participated in the first trimester combined screening in public health care in Finland during the study period of 1 May 2002 to 31 December 2008. Women at the age of 35 or more (n = 13,004) were controls. Prevalence of Down syndrome, detection rate, false positive rate and number of invasive procedures needed to detect a single case of Down syndrome were analyzed in both groups., Results: The overall prevalence of Down syndrome (n = 73) in the study group was 1:876. The number of detected cases was 54. The detection rate was 74.0% with a false positive rate of 2.8%. Number of invasive procedures needed to detect a single case of Down syndrome was 33. In the control group, the detection rate was 87.0% with a false positive rate of 11.9%. The number of invasive procedures needed to detect a single case of Down syndrome was 15. The differences in detection rate and false positive rate were significant, P < 0.012, P < 0.001, respectively., Conclusion: The overall detection rate given for the entire population is an overestimate for a woman younger than the age of 35, which should be taken into consideration when counselling women of that age., (© 2012 Blackwell Publishing Ltd.)

Objective: To investigate first trimester levels of ADAM12 in trisomy 18 and 13 pregnancies and whether incorporating ADAM12 in the LifeCycle™ risk calculation program of trisomy 18 and trisomy 13 screenings can improve the detection rates of trisomies 18 and 13., Methods: ADAM12 was incorporated in the LifeCycle™ risk calculation program. A specific algorithm with cut-off of 1:200 for screening of trisomies 18 and 13 was employed. Detection rates for trisomies 18 and 13 were calculated., Results: There was a significant difference in ADAM12 levels between trisomy 18 pregnancies and controls during the gestation weeks 9 + 0 - 10 + 6, but not thereafter. In trisomy 13 pregnancies there was no difference in weeks 9 + 0 - 10 + 6, but there was in 11 + 0 - 12 + 6. The specific algorithms for trisomies 18 and 13 combined with algorithm for trisomy 21 yielded detection rates of 73.7% and 66.7%, respectively. The combined false positive rate was 4.6%. Adding ADAM12, the detection rate for trisomy 18 was the same, at 73.7% and for trisomy 13, at 66.7%., Conclusion: ADAM12 did not improve the detection rate.

We analyzed the frequency and possible causes of false-negative (Fn) screening results in first-trimester combined Down syndrome screening in Finland. During the study period (May 1, 2002, to December 31, 2008), 76,949 voluntary women with singleton pregnancies participated in screening. Maternal age at screening, week of gestation, levels of pregnancy-associated plasma protein-A (PAPP-A), free β-human chorionic gonadotropin (fβ-hCG), and nuchal translucency (NT) measurement were compared and statistically analyzed between true-positive (Tp) and Fn cases. There were a total of 188 Down syndrome cases (1:409) in the screened population; 154 confirmed Tp and 34 Fn cases. Most Fn cases (n = 25) occurred at 12 + 0 to 13 + 6 weeks' gestation and only nine Fn cases presented between 10 and 11 weeks' gestation. According to the logistic regression analysis, the NT measurement was the most powerful discriminating factor in Fn screening results and accounted for 37.2% of Fn results. The second most important factor was fβ-hCG, adding 14.0% to R(2), followed by PAPP-A, which contributed a further 14.3%. The chosen parameters explain 83.9% of Fn results, but 16.1% remain due to unknown factor(s). All investigated parameters contributed to Fn screening results, but fetal NT was the most discriminating factor leading to an Fn screening result., (Copyright © 2012 by Thieme Medical Publishers, Inc.)

Objective: To examine the performance of first-trimester combined screening after adding the specific algorithms for trisomies 18 and 13 in the Down syndrome screening program for chromosomal abnormalities other than trisomy 21 and to determine the outcomes of such pregnancies., Design: A retrospective study., Setting: Oulu University Hospital, Finland., Population: Pregnant women (n=56 076) participating voluntarily in first-trimester combined Down syndrome screening in Northern and Eastern Finland during the study period 1 June 2002 to 31 December 2008., Methods: The data of all known cases of chromosomal abnormalities other than trisomy 21 were collected., Main Outcome Measures: Risk algorithms for trisomies 21, 18 and 13 were used for the calculation of patient-specific risks for certain chromosomal abnormalities. Algorithms were based on maternal age, crown-rump length, nuchal translucency, and measurement of free β-human chorionic gonadotrophin and pregnancy-associated plasma protein-A. Detection rates and false-positive rates were calculated., Results: A total of 27 cases of trisomy 18, 11 cases of trisomy 13 and 30 cases of other chromosomal abnormalities were analyzed. The algorithm for Down syndrome detected 55.6% of trisomy 18 cases, 36.4% of trisomy 13 cases and 60.0% of other chromosomal abnormalities. When specific risk algorithms were added, the detection rates improved for trisomy 18 (74.0%) and for trisomy 13 (54.5%), with only a slight increase of the false-positive rate of 0.2%. The detection rate for other chromosomal abnormalities did not improve., Conclusions: Adding the trisomy 18 algorithm to the Down screening program resulted in the detection of five additional trisomy 18 cases., (© 2011 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2011 Nordic Federation of Societies of Obstetrics and Gynecology.)

Objective: To evaluate the performance of first-trimester combined screening in 5-year periods according to maternal age in a low-risk population., Design: A prospective study., Setting: Multicenter study in Finland., Population: A total of 76949 voluntary women with singleton pregnancies participated in first-trimester combined screening in public healthcare between 1 May 2002 and 31 December 2008., Methods: The serum samples were analyzed using the PerkinElmer AutoDELFIA® time-resolved fluoroimmunoassay kit for the measurement of pregnancy-associated plasma protein-A and free beta-human chorionic gonadotropin. Nuchal translucency was measured by trained personnel (midwives or physicians) in a university or central hospital., Main Outcome Measures: Performance, detection rate, false positive rate and the number of invasive procedures needed to detect a single case of Down's syndrome were analyzed., Results: There was a direct connection between maternal age and the prevalence of Down's syndrome with a low prevalence in young women being 1:1 193 in the 25-29 age group and 1:150 in the 35-39 age group. Consequently, for a fixed false positive rate of 5%, the number of invasive procedures needed to detect one case of Down's syndrome is higher in younger women to achieve the same detection rate., Conclusions: In combined first trimester screening the risk for Down's syndrome is individual, varying with maternal age. This should be taken into consideration when counseling women., (© 2011 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2011 Nordic Federation of Societies of Obstetrics and Gynecology.)

The maternal serum levels of pregnancy-associated plasma protein-A (PAPP-A) were reduced in hormonally stimulated pregnancies in the in vitro fertilization and intracytoplasmic sperm injection groups (N=176; PAPP-A: 0.82) and in the entire assisted reproduction group (N=282; PAPP-A: 0.83) as compared with controls (N=24,783; PAPP-A: 0.94). However, the false-positive rate of first-trimester combined screenings was not statistically significantly increased in assisted reproduction pregnancies after adjustment for maternal age., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

We investigated the association of first trimester low maternal serum pregnancy-associated plasma protein-A (PAPP-A) levels with small-for-gestational age (SGA) newborns and stillbirths (SBs) in a retrospective national population-based register study. The study group comprised 921 women with the lowest 5% PAPP-A levels (< or =0.3 MoM) and the control group comprising 18,615 women with PAPP-A levels >0.3 MoM. In the study group there were 35 (3.8%) and in the control group 213 SGA newborns (1.1%), respectively (OR, 3.41; 95% CI, 2.37-4.91). There were 9 (1.0%) and 51 (0.3%) cases of SBs in the study and control groups, respectively (p < 0.002; OR, 3.59; 95% CI, 1.76-7.32). Low PAPP-A is a risk factor for SGA and SB.

Objective: To investigate whether incorporating the measurement of ADAM12 in the risk calculation program LifeCycle, can improve Down screening in the first trimester., Methods: In a retrospective case control study, maternal serum ADAM12 concentrations were measured and compared in Down syndrome cases (n = 53) and in controls (n = 226) obtained from first trimester (9-12 weeks) screening samples in Oulu and Kuopio University Hospitals. Median concentration ( microg/l), observed and regressed (weight corrected) MoMs of ADAM12 were calculated., Results: There was a significant difference in ADAM12 levels between Downs and controls during the pregnancy weeks 9 + 0 to 10 + 6, but not thereafter. By adding ADAM12 to the marker set used in the risk calculation program, one screening false negative Down syndrome case occurred in the affected population, which did not alter false positive rate., Conclusion: Adding ADAM12 as a parameter in Down screening did not cause radical changes in the risk value. The test might be useful at 9 and 10 weeks in which it might have the potential to improve the performance of the risk assessment especially for women receiving a result close to the high-risk cut-off. The real influence of ADAM12 remains to be elucidated in larger studies incorporating ADAM12 to the risk calculation program.

Objective: The purpose of this study was to compare the efficacy of both separate and combined maternal serum testing and fetal nuchal translucency measurement in the first trimester screening for Down syndrome in northern Finland., Study Design: The following screening tests were evaluated: measurement of nuchal translucency (NT) alone; serum screening (pregnancy-associated plasma protein A [PAPP-A] and free beta subunit of human chorionic gonadotropin [beta-hCG]) alone; and combined screening (NT plus PAPP-A and free beta-hCG)., Results: The participants comprised 7534 pregnant women during the 10+0-12+6 weeks of pregnancy. All 7534 women participated in serum screening, and 4765 women participated in combined screening. In the serum screening-alone group, there were 30 cases of trisomy 21, of which 23 (76%) were detected. In the combined-screening group, there were 24 cases of trisomy 21 and 21 (87.5%) were detected. In the combined-screening group NT alone detected 15 cases of Down syndrome (62%)., Conclusion: Combined screening is the method of choice for Down syndrome screening.

A definition has been agreed for the most senior professional (consultant) in clinical chemistry and laboratory medicine. A model job description for a consultant has been determined, which is intended to act as a toolkit to assist employing authorities and professional bodies to define the role of individual consultant posts. A total of 86 competences for a consultant have been designated and expressed in the form of simple generic proficiency standards. These competences have been allocated to six broad areas: clinical [13]; scientific [15]; technical [12]; communication [12]; management and leadership [20]; professional autonomy and accountability [14]. The competences are intended to be illustrative rather than definitive and to enable the duties of any consultant post to be defined. Assessment of competence is likely to entail consideration of qualifications, registration status, continuing professional development and performance review. The project is intended as a guide to European societies of clinical chemistry and laboratory medicine. The guide should be capable of local interpretation to encourage a greater degree of commonality in the role of the consultant whilst protecting national identity. The guide should stimulate international understanding and collaboration and contribute to an overall improvement in the quality of practice.