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Objectives The aim of this study is to determine whether combinations of specific Life’s Simple 7 (LS7) components are associated with reduced risk for heart failure (HF). Background The American Heart Association recommends the concept of LS7: healthy behaviors that have been shown to reduce cardiovascular disease. Methods A total of 37,803 participants from the EPIC-NL (European Prospective Investigation Into Cancer and Nutrition–Netherlands) cohort were included (mean age: 49.4 ± 11.9 years, 74.7% women). The LS7 score ranged from 0 to 14 and was calculated by assigning 0, 1, or 2 points for smoking, physical activity, body mass index, diet, blood pressure, total cholesterol, and blood glucose. An overall ideal score (11 to 14 points) was present in 23.2% of participants, an intermediate score (9 or 10 points) in 35.3%, and an inadequate score (0 to 8 points) in 41.5%. Results Over a median follow-up period of 15.2 years (interquartile range: 14.1 to 16.5 years), 690 participants (1.8%) developed HF. In Cox proportional hazards models, ideal and intermediate LS7 scores were associated with reduced risk for HF compared with the inadequate category (hazard ratio: 0.45 [95% confidence interval (CI): 0.34 to 0.60] and hazard ratio: 0.53 [95% CI: 0.44 to 0.64], respectively). Our analyses show that combinations with specific LS7 components, notably glucose, body mass index, smoking, and blood pressure, are associated with a lower incidence of HF. Conclusions A healthy lifestyle, as reflected in an ideal LS7 score, was associated with a 55% lower risk for HF compared with an inadequate LS7 score. Preventive strategies that target combinations of specific LS7 components could have a significant impact on decreasing incident HF in the population at large.

Objectives This study investigated adherence to drug therapy guidelines in heart failure (HF) with reduced left-ventricular ejection fraction (LVEF) of Background Despite previous surveys of HF, important uncertainties remain regarding guideline adherence in a representative real-world population. Methods A cross-sectional registry in 34 Dutch HF outpatient clinics that included 10,910 patients with the diagnosis of HF was examined. Of that number, 8,360 patients had LVEF Results In the HFrEF group, 81% of the patients were treated with loop diuretics, 84% with renin-angiotensin-system (RAS) inhibitors, 86% with β-blockers, 56% with mineralocorticoid-receptor antagonists (MRA), and 5% with If-channel inhibition. Differences in medication use were minor among the 3 groups but were significant among centers. Inability to tolerate the medications was recorded in 9.4% patients taking RAS inhibitors, 3.3% taking β-blockers, and 5.4% taking MRAs. Median loop diuretic dose was 40 mg of furosemide equivalent, RAS inhibitor dose 50% of target, β-blocker dose 25% of target, and MRA dose 12.5 mg of spironolactone equivalent. Elderly patients were treated predominantly with diuretics and less often with RAS inhibitors, β-blockers, and MRAs. Conclusions This large contemporary HF registry showed a relatively high use of evidence-based treatment, particularly in younger patients. However, the average dose of evidence-based medication was still lower than recommended by guidelines. Furthermore, the more recently introduced If-channel inhibition has hardly been adopted. There is ample room for improvement of HFrEF therapy, even more than 25 years after convincing evidence that HFrEF treatment leads to better outcome.

ObjectiveWe examined temporal heart failure (HF) prescription patterns in a large representative sample of real-world patients in the UK, using electronic health records (EHR).MethodsFrom primary and secondary care EHR, we identified 85 732 patients with a HF diagnosis between 2002 and 2015. Almost 50% of patients with HF were women and the median age was 79.1 (IQR 70.2–85.7) years, with age at diagnosis increasing over time.ResultsWe found several trends in pharmacological HF management, including increased beta blocker prescriptions over time (29% in 2002–2005 and 54% in 2013–2015), which was not observed for mineralocorticoid receptor-antagonists (MR-antagonists) (18% in 2002–2005 and 18% in 2013–2015); higher prescription rates of loop diuretics in women and elderly patients together with lower prescription rates of angiotensin-converting enzyme inhibitors and/or angiotensin II receptor blockers, beta blockers or MR-antagonists in these patients; little change in medication prescription rates occurred after 6 months of HF diagnosis and, finally, patients hospitalised for HF who had no recorded follow-up in primary care had considerably lower prescription rates compared with patients with a HF diagnosis in primary care with or without HF hospitalisation.ConclusionIn the general population, the use of MR-antagonists for HF remained low and did not change throughout 13 years of follow-up. For most patients, few changes were seen in pharmacological management of HF in the 6 months following diagnosis.

Janssen, A (reprint author), Jessa Hosp, Heartctr Hasselt, Clin Res Dept Cardiol, Hasselt, Belgium. arne.janssen@jessazh.be

Background Clinical management of heart failure with preserved ejection fraction (HFpEF) centres on treating comorbidities and is likely to vary between countries. Thus, to provide insight into the current management of HFpEF, studies from multiple countries are required. We evaluated the clinical profiles and current management of patients with HFpEF in the Netherlands. Methods We included 2153 patients with HFpEF (defined as a left ventricular ejection fraction ≥ 50%) from the CHECK-HF registry, which included patients from 2013 to 2016. Results Median age was 77 (IQR 15) years, 55% were women and the most frequent comorbidities were hypertension (51%), renal insufficiency (45%) and atrial fibrillation (AF, 38%). Patients between 65 and 80 years and those over 80 years had on average more comorbidities (up to 64% and 74%, respectively, with two or more comorbidities) than patients younger than 65 years (38% with two or more comorbidities, p-value Conclusion The medical HFpEF profile is determined by the underlying comorbidities, sex and age. Comorbidities are highly prevalent in HFpEF patients, especially in elderly HFpEF patients. Despite the lack of evidence, many HFpEF patients receive regular beta-blockers, RAS inhibitors and MRAs, often for the treatment of comorbidities.

Aims We aimed to derive and validate clinically useful clusters of patients with heart failure with preserved ejection fraction (HFpEF; left ventricular ejection fraction ≥50%). Methods and results We derived a cluster model from 6909 HFpEF patients from the Swedish Heart Failure Registry (SwedeHF) and externally validated this in 2153 patients from the Chronic Heart Failure ESC‐guideline based Cardiology practice Quality project (CHECK‐HF) registry. In SwedeHF, the median age was 80 [interquartile range 72–86] years, 52% of patients were female and most frequent comorbidities were hypertension (82%), atrial fibrillation (68%), and ischaemic heart disease (48%). Latent class analysis identified five distinct clusters: cluster 1 (10% of patients) were young patients with a low comorbidity burden and the highest proportion of implantable devices; cluster 2 (30%) patients had atrial fibrillation, hypertension without diabetes; cluster 3 (25%) patients were the oldest with many cardiovascular comorbidities and hypertension; cluster 4 (15%) patients had obesity, diabetes and hypertension; and cluster 5 (20%) patients were older with ischaemic heart disease, hypertension and renal failure and were most frequently prescribed diuretics. The clusters were reproduced in the CHECK‐HF cohort. Patients in cluster 1 had the best prognosis, while patients in clusters 3 and 5 had the worst age‐ and sex‐adjusted prognosis. Conclusions Five distinct clusters of HFpEF patients were identified that differed in clinical characteristics, heart failure drug therapy and prognosis. These results confirm the heterogeneity of HFpEF and form a basis for tailoring trial design to individualized drug therapy in HFpEF patients., Latent class analysis identified 5 patient clusters with differences in clinical characteristics in 6909 patients from the Swedish Heart Failure Registry. BMI, body mass index; COPD, chronic obstructive pulmonary disease; eGFR, estimated glomerular filtration rate; HFpEF, heart failure with preserved ejection fraction; IHD, ischaemic heart disease; NYHA, New York Heart Association.

Background European Action on Secondary and Primary Prevention by Intervention to Reduce Events (EUROASPIRE) V in primary care was carried out by the European Society of Cardiology EURObservational Research Programme in 2016–2018. The main objective was to determine whether the 2016 Joint European Societies’ guidelines on cardiovascular disease prevention in people at high cardiovascular risk have been implemented in clinical practice. Methods The method used was a cross-stional survey in 78 centres from 16 European countries. Patients without a history of atherosclerotic cardiovascular disease either started on blood pressure and/or lipid and/or glucose lowering treatments were identified and interviewed ≥ 6 months after the start of medication. Results A total of 3562 medical records were reviewed and 2759 patients (57.6% women; mean age 59.0 ± 11.6 years) interviewed (interview rate 70.0%). The risk factor control was poor with 18.1% of patients being smokers, 43.5% obese (body mass index ≥30 kg/m2) and 63.8% centrally obese (waist circumference ≥88 cm for women, ≥102 cm for men). Of patients on blood pressure lowering medication 47.0% reached the target of Conclusion The primary care arm of the EUROASPIRE V survey revealed that large proportions of people at high cardiovascular disease risk have unhealthy lifestyles and inadequate control of blood pressure, lipids and diabetes. Thus, the potential to reduce the risk of future cardiovascular disease throughout Europe by improved preventive cardiology programmes is substantial.

Aims Exergaming is a new tool to increase physical activity. This study aimed to determine the effects of access to a home-based exergame (Nintendo Wii) in patients with heart failure (HF) on exercise capacity, self-reported physical activity and patient-reported outcome measures. Methods and results We enrolled 605 HF patients in New York Heart Association functional class I-IV, independent of ejection fraction, in an international multicentre randomized controlled trial. Patients were randomized to exergame (intervention) or motivational support (control). The primary endpoint was change in submaximal aerobic exercise capacity as measured by the distance walked in 6 min (6MWT) between baseline and 3 months. Secondary endpoints included long-term submaximal aerobic exercise capacity, muscle function, self-reported physical activity, exercise motivation, exercise self-efficacy at 3, 6 and 12months. At baseline, patients on average walked 403142m on the 6MWT. Patients in the exergame group walked further compared to controls at 3 months (454123 vs. 420 +/- 127m, P = 0.005), at 6 months (452 +/- 123 vs. 426 +/- 133m, P = 0.015) and 12months (456 +/- 122 vs. 420 +/- 135m, P = 0.004). However, correcting for baseline 6MWT values by means of a linear mixed-effects model revealed no main effect for the intervention on 6MWT. Small significant effects on muscle function were found. Statistically significant treatment effects were found for muscle function but after correction for baseline and confounders, only the treatment effect for the heel-rise left at 6 months was significant (PFunding Agencies|Swedish National Science Council [K2013-69X-22302-01-3, 2016-01390]; Swedish National Science Council/Swedish Research Council for Health, Working Life and Welfare, VR-FORTE [2014-4100]; Swedish Heart and Lung AssociationSwedish Heart-Lung Foundation [E085/12]; Swedish Heart and Lung FoundationSwedish Heart-Lung Foundation [20130340, 20160439]; Vardal Foundation [2014-0018]; Medical Research Council of Southeast Sweden [FORSS 474681]

ObjectivesTelephone triage of patients suspected of transient ischaemic attack (TIA) or stroke is challenging. Both TIA and stroke more likely occur during daytime, with a peak in the morning hours. Thus, the time of calling might be a helpful determinant during telephone triage. We assessed the time of calling in patients with stroke-like symptoms who called the out-of-hours services in primary care (OHS-PC), and evaluated whether the time of calling differed between patients with TIA or stroke compared with those with mimics.DesignCross-sectional study.SettingSix OHS-PC locations in the Netherlands.Participants1269 telephone triage recordings of patients calling the OHS-PC because of stroke-like symptoms. We collected information on patient characteristics, symptoms, time of calling and urgency allocation. The final diagnosis related to each triage call was based on letters from the neurologist (retrieved from the patient’s general practitioner).Primary and secondary outcome measuresThe primary outcome measures were the time of calling hourly and 4 hourly, and the risk of TIA or stroke/hour. The secondary outcome measure was the risk ratio of TIA or stroke in the morning (08:00—12:00h) versus other hours.ResultsMean age was 68.6 (SD±18.5) years, 56.9% were women and 50.0% had a TIA or stroke. The risk ratio of TIA or stroke among people calling with stroke-like symptoms between 08:00—12:00h versus other hours was 1.13 (95% CI 1.00 to 1.28, p=0.070). After correction for age and sex, the adjusted risk ratio was 0.94 (95% CI 0.80 to 1.10, p=0.434).ConclusionIn patients who called the OHS-PC because of stroke-like symptoms, the time of calling did not differ between patients with TIA or stroke and patients with mimics.Trial registration numberThe Netherlands National Trial Registry (NTR7331).

Introduction The EUROASPIRE V survey in primary care was carried out by the European Society of Cardiology, EURObservational Research Programme in 2017–2018 and investigated the risk factor management in patients at high cardiovascular (CVD) risk in16 European countries. Purpose To provide an audit the implementation of the 2016 Joint European Societies' guidelines on CVD prevention in people at high risk of developing CVD in primary care and to see whether the practice of preventive cardiology had improved by comparison with the previous EUROASPIRE IV survey in 2014–2015. Methods All patients were free of coronary or other atherosclerotic diseasebut considered at high CVD risk since they had been started on blood pressure and/or lipid and/or glucose lowering treatments. They were interviewed and examined by means of standardized methods ≥6 months after the start of therapy. Results 2,759high CVD risk individuals (58% females), mean age 59 (SD 12) years, were interviewed and examined (participation rate 70%). The risk factor control was very poor, with less than half (47%) of patients on blood pressurelowering medication reaching the target of Conclusions The results of EUROASPIRE V clearly demonstrate that the control of blood pressure, LDL-cholesterol and diabetes in patients at high CVD risk remains poor with large proportions not achieving the targets defined in the prevention guidelines. There is a considerable potential to raise the standards of preventive cardiology and to improve the management of patients at high CVD risk in Europe. Funding Acknowledgement Type of funding source: Other. Main funding source(s): European Society of Cardiology

Cardiovascular disease (CVD) often goes unrecognized, despite symptoms frequently being present. Proactive screening for symptoms might improve early recognition and prevent disease progression or acute cardiovascular events. We studied the diagnostic value of symptoms for the detection of unrecognized atrial fibrillation (AF), heart failure (HF), and coronary artery disease (CAD) and developed a corresponding screening questionnaire. We included 100,311 participants (mean age 52 ± 9 years, 58% women) from the population-based Lifelines Cohort Study. For each outcome (unrecognized AF/HF/CAD), we built a multivariable model containing demographics and symptoms. These models were combined into one 'three-disease' diagnostic model and questionnaire for all three outcomes. Results were validated in Lifelines participants with chronic obstructive pulmonary disease (COPD) and diabetes mellitus (DM). Unrecognized CVD was identified in 1325 participants (1.3%): AF in 131 (0.1%), HF in 599 (0.6%), and CAD in 687 (0.7%). Added to age, sex, and body mass index, palpitations were independent predictors for unrecognized AF; palpitations, chest pain, dyspnea, exercise intolerance, health-related stress, and self-expected health worsening for unrecognized HF; smoking, chest pain, exercise intolerance, and claudication for unrecognized CAD. Area under the curve for the combined diagnostic model was 0.752 (95% CI 0.737-0.766) in the total population and 0.757 (95% CI 0.734-0.781) in participants with COPD and DM. At the chosen threshold, the questionnaire had low specificity, but high sensitivity. In conclusion, a short questionnaire about demographics and symptoms can improve early detection of CVD and help pre-select people who should or should not undergo further screening for CVD.

BackgroundDiagnosing heart failure (HF) is difficult, relying on medical history, symptoms, and signs only. Clinical guidelines recommend natriuretic peptides (NPs) as an additional diagnostic test, notably to exclude HF in suspected patients. NP testing has been available since 2003 for primary care in the Netherlands, but little is known about its uptake.AimTo evaluate the trend in ordering and appropriateness of NP testing in primary care.Design & settingAn observational study was performed between January 2005 and December 2013. Nine Dutch general practices participated, with 21 000 registered people (approximately 4300 aged ≥65 years).MethodThe total number of patients undergoing NP testing each year was calculated per 1000 patient years (PY) based on the total practice population. NP levels were used to assess whether NP testing was applied to exclude or confirm HF.ResultsThe number of NP testing increased from 2.5 per 1000 PY in 2005 to 14.0 per 1000 PY in 2013, with a peak in 2009 of 15.6 per 1000 PY. The proportion of participants with N-terminal B-type natriuretic peptide (NTproBNP) below 125 pg/ml (the exclusionary threshold recommended by the European Society of Cardiology [ESC] guidelines on HF) was on average 30%, and highest in the first year (47%).ConclusionAfter a rapid uptake of NP testing in primary care from 2005 onwards, the use of it seemed to stabilise after 2009, thus leaving patients who are prone to HF without an optimal diagnostic work-up.

BackgroundSerious adverse events (SAE) at out-of-hours services in primary care (OHS-PC) are rare. It most often concerns missed acute coronary syndromes (ACS). Root cause analyses highlighted errors in the triage process, but these analyses are hampered by hindsight bias.AimTo compare triage calls at the OHS-PC of missed ACS with matched controls with chest discomfort but without a missed ACS; and to assess predictors of missed ACS.MethodA case-control study with triage recordings of calls of a missed ACS registered between 2013–2017. Controls were from the same period. Cases were matched 1:8 with controls based on age and gender. Clinical, patient and call characteristics were assessed, and 15 expert GPs rated the triage safety and quality, being blinded to the final diagnosis. We applied conditional logistic regression analysis.ResultsFifteen missed ACS calls and 120 matched control calls were included. Cases used less cardiovascular medication (38.5% versus 64.1%, P = 0.05), and more often experienced retrosternal chest pain (63.3% versus 24.7%, P = 0.02) than controls. Consultation of the supervising GP (86.7% versus 49.2%, P = 0.02) occurred more often in cases than controls. Experts rated the triage of cases more often as ‘poor’ (33.3% versus 10.9%, P = 0.001), and ‘unsafe’ (73.3% versus 22.5%, PConclusionIt seems nearly impossible to differentiate missed ACS at the OHS-PC from others with chest discomfort based on symptom presentation.

Background: Prescribed dosages of heart failure (HF) therapy in patients with a reduced left ventricular ejection fraction remain lower than guideline recommended. It remains unclear whether systolic blood pressure (BP) influences prescription of HF drugs to HF patients with a reduced left ventricular ejection fraction in a European setting. This study aimed to investigate the role of systolic BP on the prescription rate and actual dose of guideline-recommended HF therapy. Methods: A total of 8246 patients with chronic HF with a reduced left ventricular ejection fraction from 34 Dutch outpatient HF clinics were included. Detailed information on prescription rates and dosages of HF drugs were assessed according to systolic BP categories ( Results: Patients with systolic BP P P for all trends, P for all trends, Conclusions: In this large cross-sectional cohort of patients with reduced left ventricular ejection fraction, patients with lower systolic BP receive more HF drugs but at lower dose relative to the target dose recommended in HF guidelines. Discussion is warranted regarding what target BP is acceptable and what should be limiting factors in uptitration to adequate levels of HF medication.

Objective The HEART score is a clinical decision support tool for physicians to stratify the risk of major adverse cardiac events (MACE) in patients presenting with chest pain at the emergency department. The score includes 5 elements, including troponin level. Our aim was to compare safety and efficiency of the HEART scores calculated by using the first representative troponin (ie, based on time since symptom onset) compared to the original HEART score, where calculation was based on the first available troponin measurement, irrespective of duration of symptoms. Methods We performed a secondary analysis on patients from the HEART-impact trial (2013-2014, the Netherlands). Two HEART scores were calculated for all patients: a HEART score with a T (troponin) element score based on the first available troponin (HEART-first) and 1 with a T element score based on the first representative troponin (ie, at least 3 hours after symptom onset; HEART-representative). We compared all patients' scores and risk categories between HEART-first and HEART-representative. Furthermore, we compared safety (proportion of patients with MACE receiving a low score) and efficiency (proportion of patients with a low score) between HEART-first and HEART-representative. Results We included 1222 patients. In 882 (72%) patients, the first troponin was representative, resulting in the same HEART-first and HEART-representative score. In the remaining 340 patients the use of HEART-representative led to a different score than HEART-first in 43 patients (3.5%). Out of the 222 patients with MACE, 11 patients (5.0%) received a low score by using HEART-first compared with 10 patients (4.5%) when using HEART-representative (P = 0.83). The number of patients with a low score was similar (P = 0.93) when using the HEART-first (464/1222; 38%) or HEART-representative score (462/1222; 38%). Conclusions Using a representative troponin measurement changed the value of the HEART score in only 3.5% of patients and had no impact on safety and efficiency of the HEART score. These results suggest there is no need to wait for a representative troponin measurement and should encourage physicians to adhere to the original HEART score guidelines.

Cardiovascular disease is a model example of a preventable condition for which practice guidelines are particularly important. In 2016, the joint task force created by the European Society of Cardiology (ESC) together with 10 other societies released the new version of the European guidelines on cardiovascular disease prevention. To facilitate the implementation of the ESC guidelines, a dedicated prevention implementation committee has been established within the European Association of Preventive Cardiology. The paper will first explore potential barriers to the guidelines' implementation. It then develops a discussion that seeks to inform the future development of the committee's work, including a new definition of the guidelines' stakeholders (health policy-makers, healthcare professionals and health educators, patient organisations, entrepreneurs and the general public), future activities within four specific areas: strengthening awareness of the guidelines among stakeholders; supporting organisational changes to facilitate the guidelines' implementation; motivating stakeholders to utilise the guidelines; and present ideas on new implementation strategies. Providing multifaceted cooperation between healthcare professionals, healthcare management executives and health policy-makers, the novel approach proposed in this paper should contribute to a wider use of the 2016 ESC guidelines and produce desired effects of less cardiovascular disease morbidity and mortality. Furthermore, the solutions presented within the paper may constitute a benchmark for the implementation of practice guidelines in other medical disciplines. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This paper was produced within the framework of the European Society of Cardiology (ESC) prevention of cardiovascular disease programme which is led by the European Association of Preventive Cardiology (EAPC) in collaboration with the Acute Cardiovascular Care Association (ACCA) and the Association of Cardiovascular Nursing and Allied Professions (ACNAP). The programme is supported by Amgen, AstraZeneca, Ferrer and Sanofi and Regeneron in the form of educational grants. Uchmanowicz, I (corresponding author), Bartla 5, PL-51618 Wroclaw, Poland. izabella.uchmanowicz@umed.wroc.pl

Background During telephone triage, it is difficult to assign adequate urgency to patients with chest discomfort. Considering the time of calling could be helpful. Objective To assess the risk of acute coronary syndrome (ACS) in certain time periods and whether sex influences this risk. Methods Cross-sectional study of 1655 recordings of telephone conversations of patients who called the out-of-hours services primary care (OHS-PC) for chest discomfort. Call time, patient characteristics, symptoms, medical history and urgency allocation of the triage conversations were collected. The final diagnosis of each call was retrieved at the patient’s general practice. Absolute numbers of patients with and without ACS were plotted and risks per hour were calculated. The risk ratio of ACS at night (0 to 9 am) was calculated by comparing to the risk at other hours and was adjusted for gender and age. Results The mean age of callers was 58.9 (standard deviation ±19.5) years, 55.5% were women and, in total, 199 (12.0%) had an ACS. The crude risk ratio for an ACS at night was 1.80 (confidence interval 1.39–2.34, P Conclusions Patients calling the OHS-PC for chest discomfort between 0 and 9 am have almost twice a higher risk of ACS than those calling other hours, a phenomenon more evident in men than in women. At night, dispatching ambulances more ‘straightaway’ could be considered for these patients with chest discomfort. Trial number NTR7331.

Atrial fibrillation (AF) is common in chronic heart failure (HF) patients and influences the choice and effects of drug and device therapy. In this large real-world HF registry, we studied whether the presence of AF affects the prescription of guideline-recommended HF therapy.We analyzed 8253 patients with chronic HF with reduced ejection fraction (HFrEF) from 34 Dutch outpatient clinics included in the period between 2013 and 2016 treated according to the 2012 ESC guidelines.2109 (25.6%) of these patients were in AF (mean age 76.8 ± 9.2 years, 65.0% were men) and 6.144 (74.4%) had no AF (mean age 70.7 ± 12.2 years, 63.6% were men). Patients with AF more often received beta-blockers (81.7% vs. 79.7%, p = 0.04), MRAs (57.1% vs. 51.7%, p < 0.01), diuretics (89.7% vs. 80.6%, p < 0.01) and digoxin (40.1% vs. 9.3%, p < 0.01) compared to patients without AF, whereas they less often receive renin-angiotensin-system (RAS)-inhibitors (76.1% vs. 83.1%, p < 0.01). The number of patients who received beta-blockers, RAS-inhibitor and MRA at ≥50% of the recommended target dose was comparable between those with and without AF (16.6% vs. 15.2%, p = 0.07).In this large cohort of chronic HFrEF patients, the prevalence of AF was high and we observed significant differences in prescription of both guideline-recommended HF between patients with and without AF.Copyright © 2020 Elsevier B.V. All rights reserved.

This is a pre-copyedited, author-produced version of an article accepted for publication in European Journal of Preventive Cardiology following peer review. The version of record Piepoli, M.F., Abreu, A., Albus, C., Ambrosetti, M., Brotons, C., Catapano, A.L. ... Tiberi, M. (2020). Update on cardiovascular prevention in clinical practice: A position paper of the European Association of Preventive Cardiology of the European Society of Cardiology*. European Journal of Preventive Cardiology (EJPC), 27(2), 181-205 is available online at: https://doi.org/10.1177/2047487319893035. European guidelines on cardiovascular prevention in clinical practice were first published in 1994 and have been regularly updated, most recently in 2016, by the Sixth European Joint Task Force. Given the amount of new information that has become available since then, components from the task force and experts from the European Association of Preventive Cardiology of the European Society of Cardiology were invited to provide a summary and critical review of the most important new studies and evidence since the latest guidelines were published. The structure of the document follows that of the previous document and has six parts: Introduction (epidemiology and cost effectiveness); Cardiovascular risk; How to intervene at the population level; How to intervene at the individual level; Disease-specific interventions; and Settings: where to intervene? In fact, in keeping with the guidelines, greater emphasis has been put on a population-based approach and on disease-specific interventions, avoiding re-interpretation of information already and previously considered. Finally, the presence of several gaps in the knowledge is highlighted.

Background: Patients who suffer a transient ischemic attack (TIA) have a high short-term risk of developing ischemic stroke, notably within the first 48 h. Timely diagnosis and urgent preventive treatment substantially reduce this risk. We conducted a systemic review to quantify patient delay in patients with (suspected) TIA, and assess determinants related to such delay. Methods: A systematic review using MEDLINE and EMBASE databases up to March 2017 to identify studies reporting the time from onset of TIA symptoms to seeking medical help. Results: We identified nine studies providing data on patient delay, published between 2006 and 2016, with 7/9 studies originating from the United Kingdom (UK). In total 1103 time-defined TIA patients (no remaining symptoms > 24 h), and 896 patients with a minor stroke (i.e., mild remaining symptoms > 24 h) were included (49.1% men, mean age 72.2 years). Patient’s delay of more than 24 h was reported in 33.1–44.4% of TIA patients, with comparable proportions for minor stroke patients. Delays were on average shorter in patients interviewed at the emergency department than among patients seen at TIA outpatient clinics. Univariably associated with a shorter delay were (1) a longer duration of symptoms, (2) motor symptoms, (3) a higher ABCD2 score, and (4) correct patient’s recognition as possible ischemic cerebrovascular event. Conclusions: More than a third of patients experiencing a TIA delays medical attention for more than a day, thus critically extending the initiation of stroke preventive treatment. There still seems to be insufficient awareness among lay people that symptoms suggestive of TIA should be considered as an emergency. Additional data and multivariable analyses are needed to define main determinants of patient delay.

Purpose As part of the approval process, regulatory authorities often require postauthorization studies that involve patient registries; it is unknown, however, whether such registry studies are adequately completed. We investigated whether registry studies for new drugs were performed as agreed at time of approval. Methods This study reviewed protocols and follow-up reports for 73 registry studies that were proposed for 43 drugs approved by the Committee for Medicinal Products for Human Use in Europe in the period 2007 to 2010. Results The data lock point of January 1, 2016, was taken to allow a 5-year follow-up period for each drug after approval. At that time, 2 studies (3%) in registries had been finalized, 19 registries (26%) had not enrolled any patients, and 52 studies (71%) were ongoing. The median enrollment was 31% (interquartile range [IQR], 6–104) of the required number of patients for 41 registry studies that had a predefined sample size, 30% (IQR, 2–101) for nonimposed registries, and 61% (IQR, 18–144) for imposed registries. Implications Enrollment of patients into postapproval registries is poor, although the results for imposed registries seem better. Currently, registries only have a limited impact on resolving gaps in the knowledge of a drug’s benefits and risks at time of marketing authorization.

Background The 1-hour rule-out high-sensitive cardiac troponin T protocol (hs-cTnT), in which a serial troponin measurement is performed 1 hour after the first to assess the possibility of acute coronary syndrome (ACS), has been implemented in the European guidelines in 2015. Our aim was to assess the safety of this protocol in low-risk patients in the Emergency Department (ED) when implemented in daily practice. Methods Patients with acute chest pain presenting to the ED of our hospital and younger than 75 years were included (May 2013 to October 2014, The Netherlands). Hs-cTnT was measured at presentation (T0) and 1-1.5 hours after T0 (T1). Patients with a first troponin (T0) ≥ 0.012 ug/l were excluded. Primary endpoint was the 6-week occurrence of major adverse cardiac events (MACEs), defined as unstable angina, acute myocardial infarction (AMI), percutaneous coronary intervention, significant stenosis managed conservatively, coronary artery bypass grafting, and death. Results Of the 374 analyzed patients, 16 patients (4.3%) developed 35 MACE. Of these 16 patients with endpoints, 3 were primarily discharged with noncardiac chest pain but returned within 6 weeks with unstable angina. Importantly, no patients experienced an AMI or died during follow-up. Conclusion No AMIs or deaths occurred after introducing the 1-hour hs-cTnT protocol to rule-out ACS in chest pain patients, but other MACE such as unstable angina occurred. Our results suggest the protocol is safe to implement in the ED in The Netherlands.

IntroductionThe early stages of chronic progressive cardiovascular disease (CVD) generally cause non-specific symptoms that patients often do not spontaneously mention to their general practitioner, and are therefore easily missed. A proactive diagnostic strategy has the potential to uncover these frequently missed early stages, creating an opportunity for earlier intervention. This is of particular importance for chronic progressive CVDs with evidence-based therapies known to improve prognosis, such as ischaemic heart disease, atrial fibrillation and heart failure.Patients with type 2 diabetes or chronic obstructive pulmonary disease (COPD) are at particularly high risk of developing CVD. In the current study, we will demonstrate the feasibility and effectiveness of screening these high-risk patients with our early diagnosis strategy, using tools that are readily available in primary care, such as symptom questionnaires (to be filled out by the patients themselves), natriuretic peptide measurement and electrocardiography.Methods and analysisThe Reviving the Early Diagnosis-CVD trial is a multicentre, cluster randomised diagnostic trial performed in primary care practices across the Netherlands. We aim to include 1300 (2×650) patients who participate in a primary care disease management programme for COPD or type 2 diabetes. Practices will be randomised to the intervention arm (performing the early diagnosis strategy during the routine visits that are part of the disease management programmes) or the control arm (care as usual). The main outcome is the number of newly detected cases with CVDs in both arms, and the subsequent therapies they received. Secondary endpoints include quality of life, cost-effectiveness and the added diagnostic value of family and reproductive history questionnaires and three (novel) biomarkers (high-sensitive troponin-I, growth differentiation factor-15 and suppressor of tumourigenicity 2). Finally newly initiated treatments will be compared in both groups.Ethics and disseminationThe protocol was approved by the Medical Ethical Committee of the University Medical Center Utrecht, the Netherlands. Results are expected in 2022 and will be disseminated through international peer-reviewed publications.Trial registration numberNTR7360.

Purpose: Knowledge of the benefits and risks of new drugs is incomplete at the time of marketing approval. Registries offer the possibility for additional, post-approval, data collection. For all new drugs, which were approved in the European Union between 2007 and 2010, we reviewed the frequency, the type, and the reason for requiring a registry.Methods: The European Public Assessment Reports, published on the website of the European Medicine Agency, were reviewed for drugs approved by the Committee for Medicinal Products for Human Use. We searched for key characteristics of these drugs, including therapeutic area (ATC1 level), level of innovation (the score is an algorithm based on availability of treatment and therapeutic effect), and procedural characteristics. In addition, we identified if these registries were defined by disease (disease registry) or exposure to a single drug (drug registry).Results: Out of 116 new drugs approved in the predefined period, for 43 (37%), 1 to 6 registry studies were identified, with a total of 73 registries. Of these 46 were disease registries and 27 (single) drug registries. For 9 drugs, the registry was a specific obligation imposed by the regulators. The level of innovation and the orphan status of the drugs were determinants positively predicting post-approval registries (OR 10.3 [95% CI 1.0-103.9] and OR 2.8 [95% CI 1.0-7.5], respectively).Conclusions: The majority of registries required by regulators are existing disease registries. Registries are an important and frequently used tool for post-approval data collection for orphan and innovative drugs.

Aims In 2007, the Heart Failure Association of the European Society of Cardiology (ESC) launched the information website heartfailurematters.org (HFM site) with the aim of creating a practical tool through which to provide advice and guidelines for living with heart failure to patients, their carers, health care professionals and the general public worldwide. The website is managed by the ESC at the European Heart House and is currently available in nine languages. The aim of this study is to describe the background, objectives, use, lessons learned and future directions of the HFM site. Methods and results Data on the number of visitor sessions on the site as measured by Google Analytics were used to explore use of the HFM site from 2010 to 2015. Worldwide, the annual number of sessions increased from 416 345 in 2010 to 1 636 368 in 2015. Most users (72–75%) found the site by using a search engine. Desktops and, more recently, smartphones were used to visit the website, accounting for 50% and 38%, respectively, of visits to the site in 2015. Conclusions Although its use has increased, the HFM site has not yet reached its full potential: fewer than 2 million users have visited the website, whereas the number of people living with heart failure worldwide is estimated to be 23 million. Uptake and use could be further improved by a continuous process of qualitative assessment of users' preferences, and the provision of professional helpdesk facilities, comprehensive information technology, and promotional support.

Essentials The widely recommended CHA2DS2-VASc shows conflicting results in contemporary validation studies. We performed a systematic review and meta-analysis of 19 studies validating CHA2DS2-VASc. There was high heterogeneity in stroke risks for different CHA2DS2-VASc scores. This was not explained by differences between setting of care, or by performing meta-regression. SummaryBackground The CHA2DS2-VASc decision rule is widely recommended for estimating stroke risk in patients with atrial fibrillation (AF), although validation studies show ambiguous and conflicting results. Objectives To: (i) review existing studies validating CHA2DS2-VASc in AF patients who are not (yet) anticoagulated; (ii) meta-analyze estimates of stroke risk per score; and (iii) explore sources of heterogeneity across the validation studies. Methods We performed a systematic literature review and random effects meta-analysis of studies externally validating CHA2DS2-VASc in AF patients not receiving anticoagulants. To explore between-study heterogeneity in stroke risk, we stratified studies to the clinical setting in which patient enrollment started, and performed meta-regression. Results In total, 19 studies were evaluated, with over two million person-years of follow-up. In studies recruiting AF patients in hospitals, stroke risks for scores of 0, 1 and 2 were 0.4% (approximate 95% prediction interval [PI] 0.2–3.2%), 1.2% (95% PI 0.1–3.8%), and 2.2% (95% PI 0.03–7.8%), respectively. These were consistently higher than those in studies recruiting patients from the open general population, with risks of 0.2% (95% PI 0.0–0.9%), 0.7% (95% PI 0.3–1.2%) and 1.5% (95% PI 0.4–3.3%) for scores of 0, 1, and 2, respectively. Heterogeneity, as reflected by the wide PIs, could not be fully explained by meta-regression. Conclusions Studies validating CHA2DS2-VASc show high heterogeneity in predicted stroke risks for different scores.

Aims: To assess the long-term effects of two treatment strategies (low threshold endoscopic desobstruction vs. conservative treatment) on urinary incontinence (UI) and urgency-frequency in boys. Methods: Boys with persistent overactive bladder symptoms treated in two tertiary referral centers between 2006 and 2009 were included. Treatment strategy in center 1 was urethrocystoscopy (UCS) and in case of obstruction urethral desobstruction and in center 2 conservative. The primary outcome was time to being dry during daytime, secondary outcomes were being dry both day and night and presence of urgency-frequency, using the “provisional” International Consultation on Incontinence Questionnaires Children's Lower Urinary Tract Symptoms (LUTS) questionnaire. Results: Median age at start of treatment was 8.0 (IQR 6.4-9.4) years in center 1 and 8.4 (IQR 6.0-10.1) years in center 2. At baseline daytime incontinence was present in 100/104 children (96%, center 1) and 37/44 (84%, center 2). In center 1, UCS was performed in 98 (93%) boys, with desobstruction in 93 (88%), while in center 2 these numbers were 16 (36%), and 5 (11%). There were no differences between groups after a mean follow-up of 5 years concerning dryness at daytime (HR 0.86, 0.56-1.30), dryness day and night (HR 0.72, 0.51-1.14), and presence of urgency-frequency (HR 0.67, 0.38-1.25). Conclusions: The benefit of a strategy including low-threshold UCS and endoscopic desobstruction in boys with urge incontinence and suspected infravesical obstruction to prevent LUTS and incontinence on the longer term could not be confirmed.

Background Cardiovascular diseases (CVD) contribute considerably to mortality and morbidity. Prevention of CVD by lifestyle change and medication is important and needs full attention. In the Netherlands an integrated programme for cardiovascular risk management (CVRM), based on the Chronic Care Model (CCM), has been introduced in primary care in many regions in recent years, but its effects are unknown. In the ZWOT-CASE study we will assess the effect of integrated care for CVRM in the region of Zwolle on two major cardiovascular risk factors: systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDL-cholesterol) in patients with or at high risk of CVD. Methods This study is a pragmatic observational study comparing integrated care for CVRM with usual care among patients aged 40–80 years with CVD (n = 370) or with a high CVD risk (n = 370) within 26 general practices. After 1 yr follow-up, primary outcomes (SBP and LDL-cholesterol level) are measured. Secondary outcomes include lifestyle habits (smoking, dietary habits, alcohol use, physical activity), risk factor awareness, 10-year risk of cardiovascular morbidity or mortality, health care consumption, patient satisfaction and quality of life. Conclusion The ZWOT-CASE study will provide insight in the effects of integrated care for CVRM in general practice in patients with CVD or at high CVD risk. Trial registration The ZWOlle Transmural Integrated Care for CArdiovaScular Risk Management Study; ClinicalTrials.gov; Identifier: NCT03428061; date of registration: 09-02-2018; This study has been retrospectively registered.

Aims: Several risk factors for incident heart failure (HF) have been previously identified, however large electronic health records (EHR) datasets may provide the opportunity to examine the consistency of risk factors across different subgroups from the general population. Methods and results: We used linked EHR data from 2000 to 2010 as part of the UK-based CALIBER resource to select a cohort of 871 687 individuals 55 years or older and free of HF at baseline. The primary endpoint was the first record of HF from primary or secondary care. Cox proportional hazards analysis was used to estimate hazard ratios for associations between risk factors and incident HF, separately for men and women and by age category: 55–64, 65–74, and > 75 years. During 5.8 years of median follow-up, a total of 47 987 incident HF cases were recorded. Age, social deprivation, smoking, sedentary lifestyle, diabetes, atrial fibrillation, chronic obstructive pulmonary disease, body mass index, haemoglobin, total white blood cell count and creatinine were associated with HF. Smoking, atrial fibrillation and diabetes showed stronger associations with incident HF in women compared to men. Conclusion: We confirmed associations of several risk factors with HF in this large population-based cohort across age and sex subgroups. Mainly modifiable risk factors and comorbidities are strongly associated with incident HF, highlighting the importance of preventive strategies targeting such risk factors for HF.

Introduction EUROASPIRE V was a cross-sectional survey carried out by the European Society of Cardiology, EURObservational Research Programme in 2016–2017 in 27 European countries Purpose To describe gender differences in lifestyle and risk factor management, and the use of cardioprotective drug therapies in patients with coronary heart disease in Europe. Methods Patients Results A total of 8,261 (25.8% females), mean age 63.6 (SD 9.6) were interviewed, with a median time between the index event and interview 1.12 years (IR 0.82–1.56). Women were older (mean age 65.4 years [SD 9.2] vs 63.0 [9.7] and had a lower level of education than men.Comparing women with men, the prevalence of the risk factors were as follows: current smoking 12.8% vs 20.7%,obesity (BMI ≥30 kg/m2) 45.7% vs 34.9%, central obesity (waist circumference ≥102 cm in men or ≥88 cm in women) 78.0% vs 51.8%, raised blood pressure (BP ≥140/90 mmHg, ≥140/80 mmHg in patients with diabetes) 47.1% vs 46.0%, elevated LDL-cholesterol (≥1.8 mmol/l) 77.9% vs 68.5% and self reported diabetes 33.1% vs 28.0%. Reported use of prophylactic drug therapies for the same comparison was: antiplatelets 91.8% vs. 92.8%; beta-blockers 81.8% vs. 80.8%; ACE inhibitors/ARBs 75.0% vs. 75.3%; and statins 76.8% vs. 82.2%. The therapeutic control of blood pressure, LDL-cholesterol and diabetes (HbA1c Conclusions The results show that women with coronary disease have higher prevalence of obesity, central obesity, elevated LDL-cholesterol and self-reported diabetes than men. There were no differences in terms of blood pressure management. All coronary patients require professional support to make lifestyle changes and manage risk factors more effectivelyin order to reduce their risk of recurrent cardiovascular events. Acknowledgement/Funding ESC-EORP supported by Amgen, Eli Lilly, Pfizer, Sanofi, Ferrer and Novo Nordisk

Aims and objectives To understand clinical reasoning and decision-making of triage nurses during telephone conversations with callers suspected of having acute cardiac events, and support from a computer decision support system (CDSS) herewith. Background In telephone triage, nurses assess the urgency of callers' conditions with clinical reasoning, often supported by CDSS. The use of CDSS may trigger interactional workability dilemmas. Design Qualitative study using principles of a grounded theory approach following COREQ criteria for qualitative research. Methods Audio-stimulated recall interviews were conducted amongst twenty-four telephone triage nurses at nine out-of-hours primary care centres (OHS-PC). Results Telephone triage nurses use clinical reasoning elements for urgency assessment. Typically in telephone triage, they interpret the vocal-but not worded-elements in communication (paralanguage) such as tone of voice and shortness of breath and create a mental image to compensate for lack of visual information. We confirmed that interactional workability dilemmas occur. Congruence, established when the CDSS supports the triage nurses' decision-making, is essential for the CDSS' value. If congruence is absent, triage nurses may apply four working strategies: (a) tinker to make CDSS final recommendation align with their own assessment, (b) overrule the CDSS recommendation, (c) comply with the CDSS recommendation or (d) transfer responsibility to the GP. Conclusion Triage nurses who assess urgency may experience absence of congruence between the CDSS and their decision-making. Awareness of how triage nurses reason and make decisions about urgency and what aspects influence their working strategies can help in achieving optimal triage of callers suspected of acute cardiac events at OHS-PC. Relevance to clinical practice Triage nurses' reasoning and their working strategies are vital for outcome of triage decisions. Understanding these processes is essential for CDSS developers and OHS-PC managers, who should value how triage nurses interact with the CDSS, while they have the benefit of callers in mind.

IntroductionIn the Netherlands, the ‘Netherlands Triage Standard’ (NTS) is frequently used as digital decision support system for telephone triage at out-of-hours services in primary care (OHS-PC). The aim of the NTS is to guarantee accessible, efficient and safe care. However, there are indications that current triage is inefficient, with overestimation of urgency, notably in suspected acute cardiovascular disease. In addition, in primary care settings the NTS has only been validated against surrogate markers, and diagnostic accuracy with clinical outcomes as the reference is unknown. In the Safety First study, we address this gap in knowledge by describing, understanding and improving the diagnostic process and urgency allocation in callers with symptoms suggestive of acute cardiovascular disease, in order to improve both efficiency and safety of telephone triage in this domain.Methods and analysisAn observational study in which 3000 telephone triage recordings (period 2014–2016) will be analysed. Information is collected from the recordings including caller and symptom characteristics and urgency allocation. The callers’ own general practitioners are contacted for the final diagnosis of each contact. We included recordings of callers with symptoms suggestive of acute coronary syndrome (ACS) or transient ischaemic attack (TIA)/stroke. With univariable and multivariable logistic regression analyses the diagnostic accuracy of caller and symptom characteristics will be analysed in terms of predictive values with urgency level, and ACS and TIA/stroke as outcomes, respectively. To further improve our understanding of the triage process at OHS-PC, we will carry out additional studies applying both quantitative and qualitative methods: (i) case-control study on serious adverse events (SAE), (ii) conversation analysis study and (iii) interview study with triage nurses.Ethics and disseminationThe Medical Ethics Committee Utrecht, the Netherlands endorsed this study (National Trial Register identification: NTR7331). Results will be disseminated at scientific conferences, regional educational sessions and publication in peer-reviewed journals.

BackgroundAtrial fibrillation (AF) increases the risk of stroke, heart failure, and all-cause mortality. AF may be asymptomatic and therefore remain undiagnosed. Devices such as single-lead electrocardiographs (ECGs) may help GPs to diagnose AF.AimTo investigate the yield of opportunistic screening for AF in usual primary care using a single-lead ECG device.Design and settingA clustered, randomised controlled trial among patients aged ≥65 years with no recorded AF status in the Netherlands from October 2014 to March 2016.MethodFifteen intervention general practices used a single-lead ECG device at their discretion and 16 control practices offered usual care. The follow-up period was 1 year, and the primary outcome was the proportion of newly diagnosed cases of AF.ResultsIn total, 17 107 older people with no recorded AF status were eligible to participate in the study. In the intervention arm, 10.7% of eligible patients (n= 919) were screened over the duration of the study year. The rate of newly diagnosed AF was similar in the intervention and control practices (1.43% versus 1.37%,P= 0.73). Screened patients were more likely to have comorbidities, such as hypertension (60.0% versus 48.7%), type 2 diabetes (24.3% versus 18.6%), and chronic obstructive pulmonary disease (11.3% versus 7.4%), than eligible patients not screened in the intervention arm. Among patients with newly diagnosed AF in intervention practices, 27% were detected by screening, 23% by usual primary care, and 50% by a medical specialist or after stroke/transient ischaemic attack.ConclusionOpportunistic screening with a single-lead ECG at the discretion of the GP did not result in a higher yield of newly detected cases of AF in patients aged ≥65 years in the community than usual care. For higher participation rates in future studies, more rigorous screening methods are needed.

Background: It has been hypothesized that widespread implementation of pneumococcal conjugate vaccination (PCV) in infancy reduces early AOM and thereby prevents further AOM episodes and associated health care resource use. Methods: We tested this hypothesis by applying an extension of the original Cox proportional hazards model (Prentice, Williams and Petersons’ total time) to individual AOM episodes recorded in pseudonymised primary care electronic health records of 18,237 Dutch children born between 2004 and 2015. Children were assigned to three groups: no-PCV (January 2004-March 2006), PCV7 (April 2006-February 2011) and PCV10 (March 2011-February 2015). Results: Of the 18,237 newborns, 6967 (38%) experienced at least one GP-diagnosed AOM episode up to the age of four years (median age at first AOM: 12 months, interquartile range: 12; total number of AOM episodes: 14,689). Time-to-first AOM was longest in the PCV10 group compared with the PCV7 and no-PCV groups (log rank test: P < 0.001); in these groups 30% had experienced a first AOM at 20, 17 and 15 months, respectively. Children in the PCV10 group had a 21% lower risk of experiencing a first AOM episode than those in the no-PCV group (hazard ratio (HR): 0.79, 95% confidence interval (CI): 0.72–0.86), while the effect was less pronounced for the PCV7 group (HR: 0.94, 95% CI: 0.87–1.02). Neither PCV7 nor PCV10 reduced the risk of AOM recurrences. Compared to no-PCV, HRs for overall AOM were 1.00 (95% CI: 0.95–1.06) and 0.89 (95% CI: 0.84–0.95) for PCV7 and PCV10, respectively. Conclusion: Our cohort study suggests that PCV postpones the onset and reduces the risk of first AOM without affecting recurrences. The impact of PCV on overall AOM in children up to the age of four years seems therefore largely attributable to the prevention of a first AOM episode.

ObjectivesSuspected transient ischaemic attack (TIA) necessitates an urgent neurological consultation and a rapid start of antiplatelet therapy to reduce the risk of early ischaemic stroke following a TIA. Guidelines for general practitioners (GPs) emphasise the urgency to install preventive treatment as soon as possible. We aimed to give a contemporary overview of both patient and physician delay.MethodsA survey at two rapid-access TIA outpatient clinics in Utrecht, the Netherlands. All patients suspected of TIA were interviewed to assess time delay to diagnosis and treatment, including the time from symptom onset to (1) the first contact with a medical service (patient delay), (2) consultation of the GP and (3) assessment at the TIA outpatient clinic. We used the diagnosis of the consulting neurologist as reference.ResultsOf 93 included patients, 43 (46.2%) received a definite, 13 (14.0%) a probable, 11 (11.8%) a possible and 26 (28.0%) no diagnosis of TIA. The median time from symptom onset to the visit to the TIA service was 114.5 (IQR 44.0–316.6) hours. Median patient delay was 17.5 (IQR 0.8–66.4) hours, with a delay of more than 24 hours in 36 (38.7%) patients. The GP was first contacted in 76 (81.7%) patients, and median time from first contact with the GP practice to the actual GP consultation was 2.8 (0.5–18.5) hours. Median time from GP consultation to TIA service visit was 40.8 (IQR 23.1–140.7) hours. Of the 62 patients naïve to antithrombotic medication who consulted their GP, 27 (43.5%) received antiplatelet therapy.ConclusionsThere is substantial patient and physician delay in the process of getting a confirmed TIA diagnosis, resulting in suboptimal prevention of an early ischaemic stroke.

Background: Efficient incorporation of e-health in patients with heart failure (HF) may enhance health care efficiency and patient empowerment. We aimed to assess the effect on self-care of (i) the European Society of Cardiology/Heart Failure Association website ‘heartfailurematters.org’ on top of usual care, and (ii) an e-health adjusted care pathway leaving out ‘in person’ routine HF nurse consultations in stable HF patients. Methods and results: In a three-group parallel-randomized trial in stable HF patients from nine Dutch outpatient clinics, we compared two interventions (heartfailurematters.org website and an e-health adjusted care pathway) to usual care. The primary outcome was self-care measured with the European Heart Failure Self-care Behaviour Scale. Secondary outcomes were health status, mortality, and hospitalizations. In total, 450 patients were included. The mean age was 66.8 ± 11.0 years, 74.2% were male, and 78.8% classified themselves as New York Heart Association I or II at baseline. After 3 months of follow-up, the mean score on the self-care scale was significantly higher in the groups using the website and the adjusted care pathway compared to usual care (73.5 vs. 70.8, 95% confidence interval 0.6–6.2; and 78.2 vs. 70.8, 95% confidence interval 3.8– 9.4, respectively). The effect attenuated, until no differences after 1 year between the groups. Quality of life showed a similar pattern. Other secondary outcomes did not clearly differ between the groups. Conclusions: Both the heartfailurematters.org website and an e-health adjusted care pathway improved self-care in HF patients on the short term, but not on the long term. Continuous updating of e-health facilities could be helpful to sustain effects. Clinical Trial registration: ClinicalTrials.gov ID NCT01755988.

Background and Purpose: A rapid serum biomarker that confirms or rules out a transient ischemic attack (TIA) would be of great value in clinical practice. We aimed to systematically review current evidence for the diagnostic accuracy of blood biomarkers in the early diagnosis of TIA. Methods: This is a systematic review with quality appraisal of individual studies using the QUADAS-2 tool. MEDLINE and EMBASE databases were searched up to May 1, 2017, to select primary diagnostic accuracy studies evaluating potential biomarkers in blood for the diagnosis of TIA or ischemic stroke. Results: Of 4,215 studies retrieved, 78 met our eligibility criteria. Forty-five studies restricted their population to ischemic stroke patients, 32 included both TIA and ischemic stroke patients, and only one study was restricted to TIA patients. In total 62/78 (79.5%) studies had a case-control design comparing TIA or stroke patients with healthy subjects. Overall, 125 single biomarkers and 5 biomarker panels were studied, with a median number of participants per study of 92.0 (interquartile range 44.8–144.5), varying from 8 to 915. Sufficient information to extract 2 × 2 tables was available for 35 (44.9%) articles, and for 60 (48.0 %) biomarkers. Several markers, such as NR2A/B (antibodies), Parkinson 7, nucleoside diphosphate kinase A, ubiquitin fusion degradation protein-1, and heart-type fatty acid binding protein, have shown moderate to high diagnostic accuracy in multiple studies. Conclusions: Although the methodological quality of studies evaluating biomarkers of brain ischemia was poor, several biomarkers have shown the potential to detect transient brain ischemia in an early phase. Diagnostic accuracy studies in suspected cases of TIA are needed to determine their true clinical value.

Background Elderly patients are underrepresented in clinical trials but comprise the majority of heart failure patients. Data on age-specific use of heart failure therapy are limited. The European Society of Cardiology heart failure guidelines provide no age-specific treatment recommendations. We investigated practice-based heart failure management in a large registry at heart failure outpatient clinics. Design and methods We studied 8351 heart failure with reduced ejection fraction patients at 34 Dutch outpatient clinics between 2013 and 2016. The mean age was 72.3 ± 11.8 years and we divided age into three categories: less than 60 years (13.9%); 60–74 years (36.0%); and 75 years and over (50.2%). Results Elderly heart failure with reduced ejection fraction patients (≥75 years) received significantly fewer beta-blockers (77.8% vs. 84.2%), renin–angiotensin system inhibitors (75.2% vs. 89.7%), mineralocorticoid receptor antagonists (50.6% vs. 59.6%) and ivabradine (2.9% vs. 9.3%), but significantly more diuretics (88.1% vs. 72.6%) compared to patients aged less than 60 years (Pfor all trends Conclusion With increasing age, heart failure with reduced ejection fraction patients less often received guideline-recommended medication prescriptions and also in a lower dosage. In addition, a lower percentage of implantable cardioverter defibrillator and cardiac resynchronisation therapy device implantation in elderly patients was observed.

ObjectiveThe diagnosis of transient ischaemic attack (TIA) based on symptoms and signs can be challenging and would greatly benefit from a rapid serum biomarker of brain ischaemia. We aimed to quantify the added diagnostic value of serum biomarkers in patients suspected of TIA beyond symptoms and signs.MethodsThis is a cross-sectional diagnostic accuracy study with a 6-month follow-up period. Participants were patients suspected of TIA by the general practitioner (GP) in whom a blood sample could be collected within 72 hours from symptom onset. A research nurse visited the participant for the blood sample and a standardised interview. The GP referred participants to the regional TIA service. An expert panel of three neurologists classified cases as TIA, minor stroke or any other diagnosis, based on all available diagnostic information including the GP’s and neurologist’s correspondence and the follow-up period. We used multivariable logistic regression analyses to quantify the diagnostic accuracy of clinical predictors and the improvement of accuracy by seven biomarkers (NR2, NR2 antibodies, PARK7, NDKA, UFD1, B-FABP and H-FABP).Results206 patients suspected of TIA participated, of whom 126 (61.2%) were diagnosed with TIA (n=104) or minor stroke (n=22) by the expert panel. The median time from symptom onset to the blood sample collection was 48.0 (IQR 28.3–56.8) hours. None of the seven biomarkers had discriminative value in the diagnosis of TIA, with C-statistics ranging from 0.45 to 0.58. The final multivariable model (C-statistic 0.83 (0.78–0.89)) consisted of eight clinical predictors of TIA/minor stroke: increasing age, a history of coronary artery disease, sudden onset of symptoms, occurrence of symptoms in full intensity, dysarthria, no history of migraine, absence of loss of consciousness and absence of headache. Addition of the individual biomarkers did not further increase the C-statistics.ConclusionsCurrently available blood biomarkers have no added diagnostic value in suspected TIA.Trial registration numberNCT01954329