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Supplemental digital content is available in the text., Objectives Serious adverse events at out-of-hours services in primary care (OHS-PC) are rare, and the most often concern is missed acute coronary syndrome (ACS). Previous studies on serious adverse events mainly concern root cause analyses, which highlighted errors in the telephone triage process but are hampered by hindsight bias. This study compared the recorded triage calls of patients with chest discomfort contacting the OHS-PC in whom an ACS was missed (cases), with triage calls involving matched controls with chest discomfort but without a missed ACS (controls), with the aim to assess the predictors of missed ACS. Methods A case-control study with data from 2013 to 2017 of 9 OHS-PC in the Netherlands. The cases were matched 1:8 with controls based on age and sex. Clinical, patient, and call characteristics were univariably assessed, and general practitioner experts evaluated the triage while blinded to the final diagnosis or the case-control status. Results Fifteen 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 pain other than retrosternal chest pain (63.3% versus 24.7%, P = 0.02) compared with controls. Consultation of the supervising general practitioner (86.7% versus 49.2%, P = 0.02) occurred more often in cases than in 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%, P < 0.001) compared with controls. Conclusions To facilitate learning from serious adverse events in the future, these should also be bundled and carefully assessed without hindsight bias and within the context of “normal” clinical practice.

Root cause analyses of serious adverse events (SAE) in out-of-hours primary care (OHS-PC) often point to errors in telephone triage. Such analyses are, however, hampered by hindsight bias. We assessed whether experts, blinded to the outcome, recognize (un)safety of triage of patients with chest discomfort, and we quantified inter-rater reliability.This is a case-control study with triage recordings from 2013-2017 at OHS-PC. Cases were missed acute coronary syndromes (ACSs, considered as SAE). These cases were age- and gender-matched 1:8 with the controls, sampled from the remainder of people calling for chest discomfort. Fifteen experts listened to the recordings and rated the safety of triage. We calculated sensitivity and specificity of recognizing an ACS and the intraclass correlation.In total, 135 calls (15 SAE, 120 matched controls) were relistened. The experts identified ACSs with a sensitivity of 0.86 (95% CI: 0.71-0.95) and a specificity of 0.51 (95% CI: 0.43-0.58). Cases were rated significantly more often as unsafe than the controls (73.3% vs. 22.5%, P0.001). The inter-rater reliability for safety was poor: ICC 0.16 (95% CI: 0.00-0.32).Blinded experts rated calls of missed ACSs more often as unsafe than matched control calls, but with a low level of agreement among the experts.

Aims To assess whether a single training session for general practitioners (GPs) improves the evidence-based drug treatment of heart failure (HF) patients, especially of those with HF with reduced ejection fraction (HFrEF). Methods and results A cluster randomised controlled trial was performed for which patients with established HF were eligible. Primary care practices (PCPs) were randomised to care-as-usual or to the intervention group in which GPs received a half-day training session on HF management. Changes in HF medication, health status, hospitalisation and survival were compared between the two groups. Fifteen PCPs with 200 HF patients were randomised to the intervention group and 15 PCPs with 198 HF patients to the control group. Mean age was 76.9 (SD 10.8) years; 52.5% were female. On average, the patients had been diagnosed with HF 3.0 (SD 3.0) years previously. In total, 204 had HFrEF and 194 HF with preserved ejection fraction (HFpEF). In participants with HFrEF, the use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers decreased in 6 months in both groups [5.2%; (95% confidence interval (CI) 2.0–10.0)] and 5.6% (95% CI 2.8–13.4)], respectively [baseline-corrected odds ratio (OR) 1.07 (95% CI 0.55–2.08)], while beta-blocker use increased in both groups by 5.2% (95% CI 2.0–10.0) and 1.1% (95% CI 0.2–6.3), respectively [baseline-corrected OR 0.82 (95% CI 0.42–1.61)]. For health status, hospitalisations or survival after 12–28 months there were no significant differences between the two groups, also not when separately analysed for HFrEF and HFpEF. Conclusion A half-day training session for GPs does not improve drug treatment of HF in patients with established HF.

Aims To evaluate whether integrated care for atrial fibrillation (AF) can be safely orchestrated in primary care. Methods and results The ALL-IN trial was a cluster randomized, open-label, pragmatic non-inferiority trial performed in primary care practices in the Netherlands. We randomized 26 practices: 15 to the integrated care intervention and 11 to usual care. The integrated care intervention consisted of (i) quarterly AF check-ups by trained nurses in primary care, also focusing on possibly interfering comorbidities, (ii) monitoring of anticoagulation therapy in primary care, and finally (iii) easy-access availability of consultations from cardiologists and anticoagulation clinics. The primary endpoint was all-cause mortality during 2 years of follow-up. In the intervention arm, 527 out of 941 eligible AF patients aged ≥65 years provided informed consent to undergo the intervention. These 527 patients were compared with 713 AF patients in the control arm receiving usual care. Median age was 77 (interquartile range 72–83) years. The all-cause mortality rate was 3.5 per 100 patient-years in the intervention arm vs. 6.7 per 100 patient-years in the control arm [adjusted hazard ratio (HR) 0.55; 95% confidence interval (CI) 0.37–0.82]. For non-cardiovascular mortality, the adjusted HR was 0.47 (95% CI 0.27–0.82). For other adverse events, no statistically significant differences were observed. Conclusion In this cluster randomized trial, integrated care for elderly AF patients in primary care showed a 45% reduction in all-cause mortality when compared with usual care.

Background Heart failure (HF) and chronic obstructive pulmonary disease (COPD) often remain undiagnosed in older individuals, although both disorders inhibit functionality and impair health. The aim of the study was to assess the effectiveness of a case-finding strategy of these disorders. Methods This is a clustered randomized trial; 18 general practices from the vicinity of Utrecht, the Netherlands, were randomly allocated to a case-finding strategy or usual care. Multimorbid community subjects (≥65 years) with dyspnea or reduced exercise tolerance were eligible for inclusion. The case-finding strategy consisted of history taking, physical examination, blood tests, electrocardiography, spirometry, and echocardiography. Subsequent treatment decisions were at the discretion of the general practitioner. Questionnaires regarding health status and functionality were filled out at baseline and after 6 months of follow-up. Information regarding changes in medication and health care use during the 6 months follow-up was extracted. Results A total of 829 participants were randomized: 389 in the case-finding strategy group and 440 in the usual care group. More patients in the case-finding group received a new diagnosis of HF or COPD than the usual care group (cumulative incidence 34% vs 2% and 17% vs. 2%, respectively). Scores for health status, functionality, and health care use were similar between the 2 strategies after 6 months of follow-up. Conclusions A case-finding strategy applied in primary care to multimorbid older people with dyspnea or reduced exercise tolerance resulted in a number of new diagnoses of HF and COPD but did not result in short-term improvement of health status compared to usual care.

Background Diabetes has strongly been linked to atrial fibrillation, ischaemic heart disease and heart failure. The epidemiology of these cardiovascular diseases is changing, however, due to changes in prevalence of obesity-related conditions and preventive measures. Recent population studies on incidence of atrial fibrillation, ischaemic heart disease and heart failure in patients with diabetes are needed. Methods A dynamic longitudinal cohort study was performed using primary care databases of the Julius General Practitioners’ Network. Diabetes status was determined at baseline (1 January 2014 or upon entering the cohort) and participants were followed-up for atrial fibrillation, ischaemic heart disease and heart failure until 1 February 2019. Age and sex-specific incidence and incidence rate ratios were calculated. Results Mean follow-up was 4.2 years, 12,168 patients were included in the diabetes group, and 130,143 individuals in the background group. Incidence rate ratios, adjusted for age and sex, were 1.17 (95% confidence interval 1.06–1.30) for atrial fibrillation, 1.66 (1.55–1.83) for ischaemic heart disease, and 2.36 (2.10–2.64) for heart failure. Overall, incidence rate ratios were highest in the younger age categories, converging thereafter. Conclusion There is a clear association between diabetes and incidence of the major chronic progressive heart diseases, notably with heart failure with a more than twice increased risk.

Background/Purpose Heart failure with preserved ejection fraction (HFpEF) is currently hard to treat, and more prevalent in women as compared to men. Therefore, focus on prevention is key. Concentric remodelling is considered a pre-stage of HFpEF, yet knowledge on distributions and risk factor relations are scarce. Therefore, we identified the prevalence of early remodelling in women and men, and studied risk factors for early remodelling in women and men at risk for heart failure. Methods Clinical and echocardiographic data from 880 individuals, included in the HELPFul cohort were analysed (mean age 62.9 ±SD 9.3 years, 68.6% women). Relative wall thickness was calculated with the formula (2*LVPWD)/LVEDD and expressed as percentage. Concentric remodelling was defined as a relative wall thickness >42%. The relationship of classical cardiovascular risk factors, anthropometric -, lifestyle -, and pregnancy factors with relative wall thickness was tested using uni- and multivariable analyses for women and men separately. The association of continuous variables with relative wall thickness was analysed per standard deviation (SD) increase. Results Relative wall thickness was similar for both men (mean 43.2 ±SD 9.5) and women (mean 42.6 ±SD 8.1). Concentric remodelling (RWT >42%) was present in 49.1% of the population. Multivariable analyses showed that age, heart rate, systolic blood pressure, hypertension, and the usage of antihypertensive medication were independently associated with relative wall thickness in women. In men, heart rate and hypertension were independently associated with relative wall thickness. No associations were found for lifestyle factors such as smoking and alcohol intake. In women, there was no significant association of hypertensive pregnancy disorders and gestational diabetes with relative wall thickness. When relative wall thickness was dichotomized with >42% as cut-off for concentric remodelling the same risk factors remained independently associated in women. Per SD increase age, systolic blood pressure, heart rate, a diagnosis of hypertension and usage of antihypertensive medication were associated with an increased risk of concentric remodelling (OR=1.39 (95% CI: 1.18–1.64), 1.27 (95% CI: 1.05–1.53), 1.32 (95% CI: 1.10–1.58), 1.61 (95% CI: 1.09–2.36) and 1.67 (95% CI: 1.16–2.43), respectively) (Figure 1). In men, only a diagnosis of hypertension was a risk factor for concentric remodelling (OR=1.80 (95% CI: 1.05–3.06)). Conclusion Left ventricular concentric remodelling was as common in women as in men visiting outpatient cardiology clinics and found in half of the population. No sex-specific -, or lifestyle related risk factors could be identified. A relation with hypertension was evident in both sexes, but surprisingly no association of hypertensive pregnancy disorders was found. Concentric remodelling in women and men remains a common, but poorly understood, phenomenon that warrants further attention. Funding Acknowledgement Type of funding sources: None.

Background Superficial venous thrombosis (SVT) is considered a benign thrombotic condition in most patients. However, it also can cause serious complications, such as clot progression to deep venous thrombosis (DVT) and pulmonary embolism (PE). Although most SVT patients are encountered in primary healthcare, studies on SVT nearly all were focused on patients seen in the hospital setting. This paper describes the protocol of the development and external validation of three prognostic prediction models for relevant clinical outcomes in SVT patients seen in primary care: (i) prolonged (painful) symptoms within 14 days since SVT diagnosis, (ii) for clot progression to DVT or PE within 45 days and (iii) for clot recurrence within 12 months. Methods Data will be used from four primary care routine healthcare registries from both the Netherlands and the UK; one UK registry will be used for the development of the prediction models and the remaining three will be used as external validation cohorts. The study population will consist of patients ≥18 years with a diagnosis of SVT. Selection of SVT cases will be based on a combination of ICPC/READ/Snowmed coding and free text clinical symptoms. Predictors considered are sex, age, body mass index, clinical SVT characteristics, and co-morbidities including (history of any) cardiovascular disease, diabetes, autoimmune disease, malignancy, thrombophilia, pregnancy or puerperium and presence of varicose veins. The prediction models will be developed using multivariable logistic regression analysis techniques for models i and ii, and for model iii, a Cox proportional hazards model will be used. They will be validated by internal-external cross-validation as well as external validation. Discussion There are currently no prediction models available for predicting the risk of serious complications for SVT patients presenting in primary care settings. We aim to develop and validate new prediction models that should help identify patients at highest risk for complications and to support clinical decision making for this understudied thrombo-embolic disorder. Challenges that we anticipate to encounter are mostly related to performing research in large, routine healthcare databases, such as patient selection, endpoint classification, data harmonisation, missing data and avoiding (predictor) measurement heterogeneity.

Making a firm diagnosis of chronic heart failure with preserved ejection fraction (HFpEF) remains a challenge. We recommend a new stepwise diagnostic process, the ‘HFA–PEFF diagnostic algorithm’. Step 1 (P=Pre-test assessment) is typically performed in the ambulatory setting and includes assessment for HF symptoms and signs, typical clinical demographics (obesity, hypertension, diabetes mellitus, elderly, atrial fibrillation), and diagnostic laboratory tests, electrocardiogram, and echocardiography. In the absence of overt non-cardiac causes of breathlessness, HFpEF can be suspected if there is a normal left ventricular ejection fraction, no significant heart valve disease or cardiac ischaemia, and at least one typical risk factor. Elevated natriuretic peptides support, but normal levels do not exclude a diagnosis of HFpEF. The second step (E: Echocardiography and Natriuretic Peptide Score) requires comprehensive echocardiography and is typically performed by a cardiologist. Measures include mitral annular early diastolic velocity (e′), left ventricular (LV) filling pressure estimated using E/e′, left atrial volume index, LV mass index, LV relative wall thickness, tricuspid regurgitation velocity, LV global longitudinal systolic strain, and serum natriuretic peptide levels. Major (2 points) and Minor (1 point) criteria were defined from these measures. A score ≥5 points implies definite HFpEF; ≤1 point makes HFpEF unlikely. An intermediate score (2–4 points) implies diagnostic uncertainty, in which case Step 3 (F1: Functional testing) is recommended with echocardiographic or invasive haemodynamic exercise stress tests. Step 4 (F2: Final aetiology) is recommended to establish a possible specific cause of HFpEF or alternative explanations. Further research is needed for a better classification of HFpEF.

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Background: In the Netherlands, a digital decision support system for telephone triage at out-of-hours services in primary care (OHS-PC) is used. Differences in help-seeking behavior between men and women when transient ischemic attack (TIA) or stroke is suspected could potentially affect telephone triage and allocation of urgency.Aim: To assess patient and call characteristics and allocated urgencies between women and men who contacted OHS-PC with suspected TIA/stroke.Methods: A cross-sectional study of 1,266 telephone triage recordings of subjects with suspected neurological symptoms calling the OHS-PC between 2014 and 2016. The allocated urgencies were derived from the electronic medical records of the OHS-PC and the final diagnosis from the patient's own general practitioner, including diagnoses based on hospital specialist letters.Results: Five hundred forty-six men (mean age = 67.3 ± 17.1) and 720 women (mean age = 69.6 ± 19.5) were included. TIA/stroke was diagnosed in 294 men (54%) (mean age = 72.3 ± 13.6) and 366 women (51%) (mean age = 78.0 ± 13.8). In both genders, FAST (face-arm-speech test) symptoms were common in TIA/stroke (men 78%, women 82%) but also in no TIA/stroke (men 63%, women 62%). Men with TIA/stroke had shorter call durations than men without TIA/stroke (7.10 vs. 8.20 min, p = 0.001), whereas in women this difference was smaller and not significant (7.41 vs. 7.56 min, p = 0.41). Both genders were allocated high urgency in 75% of the final TIA/stroke cases.Conclusion: Overall, patient and call characteristics are mostly comparable between men and women, and these only modestly assist in identifying TIA/stroke. There were no gender differences in allocated urgencies after telephone triage in patients with TIA/stroke.

ObjectivesTo identify clinical variables that are associated with the diagnosis acute coronary syndrome (ACS) in women and men with chest discomfort who contact out-of-hours primary care (OHS-PC) by telephone, and to explore whether there are indications whether these variables differ among women and men.DesignCross-sectional study in which we compared patient and call characteristics of triage call recordings between women with and without ACS, and men with and without ACS.SettingNine OHS-PC in the Netherlands.Participants993 women and 802 men who called OHS-PC for acute chest discomfort (pain, pressure, tightness or discomfort) between 2014 and 2016.Primary outcome measureDiagnosis of ACS retrieved from the patient’s medical record in general practice, including hospital specialists’ discharge letters.ResultsAmong 1795 patients (mean age 58.8 (SD 19.5) years, 55.3% women), 15.0% of men and 8.6% of women had an ACS. In both sexes, retrosternal chest pain was associated with ACS (women with ACS vs without 62.3% vs 40.3%, p=0.002; men with ACS vs without 52.5% vs 39.7%, p=0.032; gender interaction, p=0.323), as was pressing/heavy/tightening pain (women 78.6% vs 61.5%, p=0.011; men 82.1% vs 57.4%, p=Ambulances were dispatched equally in women (72.9%) and men with ACS (70.0%).ConclusionOur results indicate there were more similarities than differences in symptoms associated with the diagnosis ACS for women and men. Important exceptions were pain severity and radiation of pain in women. Whether these differences have an impact on predicting ACS needs to be further investigated with multivariable analyses.Trial registration numberNTR7331.

Background Home telemonitoring in heart failure (HF) patients may reduce workload of HF nurses by reducing face-to-face contacts. The aim of this study is to assess whether telemonitoring as a substitution could have negative effects as expressed by less reduction in circulating natriuretic peptide levels between baseline and one-year of follow up compared to usual care. Methods A post-hoc analysis of the e-Vita HF trial, a three-arm parallel randomized trial conducted in stable HF patients. Patients were randomized into three arms: (i) usual HF outpatient care, (ii) usual care combined with the use of the website heartfailurematters.org, and (iii) telemonitoring (e-Vita HF platform) instead of face-to-face consultations. Mixed linear model analyses were applied to assess differences in the N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels between the three arms over a year. Results A total of 223 participants could be included (mean age 67.1 ± 10.1 years, 27% women, New York Heart Association class I–IV; 39%, 38%, 14%, and 9%). The mean left ventricular ejection fraction was 35 ± 10%. The median of routine face-to-face contacts over a year was 1.0 lower (2.0 vs. 3.0) in the third arm compared with usual care. Median NT-proBNP levels did not significantly differ between the three arms. Conclusion In stable and optimally treated HF patients, telemonitoring causing a reduction of routine face-to-face contacts seems not to negatively affect hemodynamic status as measured by NT-proBNP levels over time.

Background and Aims Impaired kidney function increase the risk of cardiovascular disease. However, it remains unclear whether this crosstalk between organs already exists at early stages in the disease trajectory and whether this risk varies with age and other factors. We aim to investigate the association between renal dysfunction and early structural and functional cardiac abnormalities in a cohort of participants referred to a cardiology outpatient department. Method We included participants from HELPFul (i.e. HEart failure with Preserved ejection Fraction in patients at risk for cardiovascular disease), a case-cohort study at Dutch cardiology outpatient clinics, who were aged 45 years and older without history of cardiovascular disease. A random sample of participants enriched with cases (defined as an early filling (E) to early diastolic mitral annular velocity (e’) (E/e’) ratio of ≥8 measured with echocardiography) was included in our study. Routine care measurements, including echocardiography and laboratory testing at the outpatient clinic were collected for all participants. An expert panel decided on presence or absence of heart failure with preserved ejection fraction (HFpEF), and left ventricular diastolic dysfunction (LVDD), guided by available international guidelines. The association between renal function, in terms of estimated glomerular filtration rate (eGFR) categories, and diagnosis of HFpEF and LVDD was assessed with multivariable logistic regression analyses, adjusted for cardiovascular and lifestyle risk factors. The association between renal function, in terms of creatinine and cystatin C levels, and echocardiographic parameters, including E/e’ ratio, LAVI (Left atrial volume index), LVMI (left ventricular mass index), and E/A (early (E) to late (A) ventricular filling ratio, was assessed with multivariable linear regression analyses, adjusted for age, sex, cardiovascular and lifestyle risk factors. Adjusted odds ratios (OR) were reported and the corresponding 95% confidence interval (95%CI). Results 777 participants were included, mean age 62.9 (SD: 9.3) years, 67.3% were female. Hundred and fifty-six (20.1%) participants had mild renal dysfunction (eGFR: 60-89 ml/min/1.73 m2), and 24 (3.1%) moderate renal dysfunction (eGFR: 30-59 ml/min/1.73 m2). HFpEF and LVDD was more common in participants with moderate renal dysfunction (13% and 33%, respectively) than in those with normal renal function (6% and 16%, respectively). In the multivariable regression model. participants with both mild and moderate renal dysfunction had a higher likelihood of being diagnosed with HFpEF (OR: 2.82, 95%CI: 1.32 to 5.91; and OR: 5.37, 95%CI: 1.11 to 19.88, respectively), LVDD (OR: 2.08, 95%CI: 1.28 to 3.36; and OR: 2.92, 95%CI: 1.04 to 7.55, respectively), compared with participants with a normal renal function. However, no significant association between creatinine or cystatin C with E/e’, LAVI, LVMI, and E/A ratio was found after adjustment for age, sex, and cardiovascular risk and lifestyle factors. Conclusion Mild renal dysfunction is related to both LVDD and HFpEF, however, this might be partly explained by a higher age in patients with renal dysfunction. Further studies are warranted to determine if preventive cardiac treatment in patients with early renal dysfunction will benefit clinical outcomes.

Background: The prognosis of women and men with persistent anginal complaints and non-obstructed coronary arteries is impaired as compared with asymptomatic women and men. The increased healthcare burden in the hospital due to repeated coronary angiography in these women and men has been documented, yet little is known about the percentage of women and men who remain symptomatic and under care of the general practitioner in the years following a coronary angiographic outcome of non-obstructed coronary arteries.Methods: From the Utrecht Coronary Biobank study, including individuals who underwent a coronary angiography from 2011 to 2015 (N = 2,546, 27% women), we selected women and men with non-obstructed coronary arteries (N = 687, 39% women). This population was linked to the Julius General Practitioners Network (JGPN); a database with routine care data of general practitioners. For every individual with non-obstructed coronary arteries, we selected an asymptomatic non-referred age-, sex-, and general practitioner-matched individual from the JGPN. We compared the healthcare consumption of men and women with non-obstructed coronary arteries to these matched individuals. The McNemar's test was used for pairwise comparison, and sex differences were assessed using stratified analyses.Results: The prevalence of non-obstructed coronary arteries was higher in women as compared with men (39 vs. 23%). During a median follow-up of 7 years [IQR 6.4–8.0], 89% of the individuals with non-obstructed coronary arteries (91% women and 87% men) visited their general practitioner for one or more cardiovascular consultations. This was compared to 34% of the matched individuals (89 vs. 34%, p < 0.001). The consultations were most often for angina (equivalents) (57 vs. 11%, p < 0.001) and heart failure (10 vs. 2%, p = 0.015). In addition, they more often consulted the general practitioner for psychosocial complaints (31 vs. 15%, p = 0.005). Findings were similar for women and men.Conclusions: A coronary angiographic outcome of non-obstructed coronary arteries is more common in women than in men. In the years following the coronary angiography, the majority of the population remains symptomatic. Both women and men with non-obstructed coronary arteries had higher health needs for angina, heart failure, and psychosocial complaints than matched asymptomatic individuals.

Background Therapeutic inertia is considered to be an obstacle to effective blood pressure (BP) control. Aims To identify patient characteristics associated with therapeutic inertia in patients with hypertension managed in primary care and to assess reasons not to intensify therapy. Methods A Dutch cohort study was conducted using electronic health record data of patients registered in the Julius General Practitioners' Network (n = 530 564). Patients with a diagnosis of hypertension, SBP at least 140 and/or DBP at least 90 mmHg, and one or two BP-lowering drug(s) were included. Therapeutic inertia was defined as not undertaking therapeutic action in follow-up despite uncontrolled BP. Multivariable logistic regression was used to identify characteristics associated with inertia. Furthermore, an exploratory survey was performed in which general practitioners of 114 patients were asked for reasons not to intensify treatment. Results We identified 6400 (10% of all patients with hypertension) uncontrolled patients on one or two BP-lowering drugs. Therapeutic inertia was 87%, similar in men and women. Older age, lower systolic, diastolic and near-target SBP, and diabetes were positively associated, while renal insufficiency and heart failure were inversely related to inertia. General practitioners did not intensify therapy because they first, considered office BP measurements as nonrepresentative (27%); second, waited for next BP readings (21%); third, wanted to optimize lifestyle first (19%). Eleven percent of patients explicitly did not want to change treatment. Conclusion Therapeutic inertia is common in primary care patients with uncontrolled hypertension. Older age, and closer to target BP, but also concurrent diabetes were associated with inertia.

Self-care is essential in the long-term management of chronic heart failure. Heart failure guidelines stress the importance of patient education on treatment adherence, lifestyle changes, symptom monitoring and adequate response to possible deterioration. Self-care is related to medical and person-centred outcomes in patients with heart failure such as better quality of life as well as lower mortality and readmission rates. Although guidelines give general direction for self-care advice, health care professionals working with patients with heart failure need more specific recommendations. The aim of the management recommendations in this paper is to provide practical advice for health professionals delivering care to patients with heart failure. Recommendations for nutrition, physical activity, medication adherence, psychological status, sleep, leisure and travel, smoking, immunization and preventing infections, symptom monitoring, and symptom management are consistent with information from guidelines, expert consensus documents, recent evidence and expert opinion. Jaarsma, T (corresponding author), Univ Linkoping, Fac Hlth Sci, Kungsgatan 40, S-60174 Norrkoping, Sweden. tiny.jaarsma@liu.se

ObjectiveClinical prediction rules (CPRs) followed by D-dimer testing were shown to safely rule out venous thromboembolism (VTE) in about half of all suspected patients in controlled and experienced study settings. Yet, its real-life impact in primary care is unknown. The aim of this study was to determine the real-life impact of CPRs for suspected VTE in primary care.DesignCross-sectional cohort study.SettingPrimary care in the Netherlands.ParticipantsPatients with suspected deep venous thrombosis (n=993) and suspected pulmonary embolism (n=484).InterventionsGeneral practitioners received an educational instruction on how to use CPRs in suspected VTE. We did not rectify incorrect application of the CPR in order to mimic daily clinical care.Main outcome measuresPrimary outcomes were the diagnostic failure rate, defined as the 3-month incidence of VTE in the non-referred group, and the efficiency, defined as the proportion of non-referred patients in the total study population. Secondary outcomes were determinants for and consequences of incorrect application of the CPRs.ResultsIn 267 of the included 1477 patients, VTE was confirmed. When CPRs were correctly applied, the failure rate was 1.51% (95% CI 0.77 to 2.86), and the efficiency was 58.1% (95% CI 55.2 to 61.0). However, the CPRs were incorrectly applied in 339 patients, which resulted in an increased failure rate of 3.31% (95% CI 1.07 to 8.76) and a decreased efficiency of 35.7% (95% CI 30.6 to 41.1). The presence of concurrent heart failure increased the likelihood of incorrect application (adjusted OR 3.26; 95% CI 1.47 to 7.21).ConclusionsCorrect application of CPRs for VTE in primary care is associated with an acceptable low failure rate at a high efficiency. Importantly, in nearly a quarter of patients, the CPRs were incorrectly applied that resulted in a higher failure rate and a considerably lower efficiency.

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).

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.

ObjectiveTo assess the accuracy of semi-automatic assisted telephone triage in patients with acute chest discomfort against the diagnosis of acute coronary syndrome (ACS) or other life-threatening events (LTEs).MethodsA cross-sectional study was performed of telephone conversations with 2023 patients with acute chest discomfort (pain, pressure, tightness or discomfort) who called out-of-hours services for primary care (OHS-PC) between 2014 and 2016. Sensitivity, specificity, positive and negative predicted values were calculated for a high urgency (patient seen within one hour) against the diagnoses of ACS and other LTEs. Diagnoses were retrieved from the patients' medical records in general practice, including hospital specialists' discharge letters.ResultsOf 2023 patients who called because of chest discomfort, 227 (11.2%) had an ACS (men 14.9%, women 8.2%) and 58 (2.9%) had another LTE (men 3.6%, women 2.3%). The sensitivity and specificity of a high Netherlands Triage System (NTS) urgency allocation against ACS/other LTEs were 0.73 (95% CI 0.68 to 0.78) and 0.43 (95% CI 0.40 to 0.45), respectively. In 13.2% of the calls the triage nurse overruled the NTS urgency, mostly by upscaling (11.0%). The sensitivity and specificity of the final urgency allocation were 0.86 (95% CI 0.81 to 0.90) and 0.34 (95% CI 0.32 to 0.37). The positive and negative predictive values of the final urgency were 0.18 (95% CI 0.17 to 0.19) and 0.94 (95% CI 0.92 to 0.95), respectively.ConclusionsThe semi-automatic triage NTS tool underestimated the urgency in 27% of patients with ACS/other LTEs. Overruling by triage nurses improved safety, but still 14% of men and women with ACS/other LTEs received too low urgency, while efficiency remained poor.Trial registration numberNTR7331.

Contains fulltext : 229321.pdf (Publisher’s version ) (Open Access) Left ventricular diastolic dysfunction (LVDD) and heart failure with preserved ejection fraction (HFpEF) are microcirculation defects following diabetes mellitus (DM). Unrecognized HFpEF is more prevalent in women with diabetes compared to men with diabetes and therefore sex-specific diagnostic strategies are needed. Previously, we demonstrated altered plasma miRs in DM patients with microvascular injury [defined by elevated plasma Angiopoietin-2 (Ang-2) levels]. This study hypothesized the presence of sex-differences in plasma miRs and Ang-2 in diabetic (female) patients with LVDD or HFpEF. After a pilot study, we assessed 16 plasma miRs in patients with LVDD (n = 122), controls (n = 244) and female diabetic patients (n = 10). Subsequently, among these miRs we selected and measured plasma miR-34a, -224 and -452 in diabetic HFpEF patients (n = 53) and controls (n = 52). In LVDD patients, miR-34a associated with Ang-2 levels (R(2) 0.04, R = 0.21, p = 0.001, 95% CI 0.103-0.312), with plasma levels being diminished in patients with DM, while women with an eGFR

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 The Netherlands Triage Standard (NTS) is a widely used decision support tool for telephone triage at Dutch out-of-hours primary care services (OHS-PC), which, however, has never been validated against clinical outcomes. We aimed to determine the accuracy of the NTS urgency allocation for patients with neurological symptoms suggestive of a transient ischaemic attack (TIA) or stroke, with the clinical outcomes TIA, stroke, and other (neurologic) life-threatening events (LTEs) as the reference. Method A cross-sectional study of telephone triage recordings of patients with neurological symptoms calling the OHS-PC between 2014 and 2016.The allocated NTS urgencies were derived from the electronic medical records of the OHS-PC. The clinical outcomes were retrieved from the electronic medical records of the patients’ own general practitioners. The accuracy of a high NTS urgency allocation (medical help within 3 h) was calculated in terms of sensitivity, specificity, positive and negative predictive values (PPV and NPV) with the clinical outcomes TIA/stroke/other LTEs as the reference. Results Of 1269 patients, 635 (50.0%) received the diagnosis TIA/stroke (34.2% TIA/minor stroke, 15.8% major ischaemic or haemorrhagic stroke), and 4.8% other LTEs. For TIA/stroke/other LTEs, the sensitivity and specificity of the NTS urgency allocation were 0.72 (95%CI 0.68–0.75) and 0.48 (95%CI 0.43–0.52), and the PPV and NPV were 0.62 (95%CI 0.60–0.64) and 0.58 (95%CI 0.54–0.62). Conclusions The NTS decision support tool used in Dutch OHS-PC performed poor to moderately regarding safety (sensitivity) and efficiency (specificity) in allocating adequate urgencies to patients with and without TIA/stroke/other LTEs. Trial registration The Netherlands National Trial Register, identification number NTR7331 /Trial NL7134.

Background Timely recognition of patients with acute coronary syndromes ( ACS ) is important for successful treatment. Previous research has suggested that women with ACS present with different symptoms compared with men. This review assessed the extent of sex differences in symptom presentation in patients with confirmed ACS . Methods and Results A systematic literature search was conducted in PubMed, Embase, and Cochrane up to June 2019. Two reviewers independently screened title‐abstracts and full‐texts according to predefined inclusion and exclusion criteria. Methodological quality was assessed using the Newcastle‐Ottawa Scale. Pooled odds ratios ( OR ) with 95% CI of a symptom being present were calculated using aggregated and cumulative meta‐analyses as well as sex‐specific pooled prevalences for each symptom. Twenty‐seven studies were included. Compared with men, women with ACS had higher odds of presenting with pain between the shoulder blades ( OR 2.15; 95% CI , 1.95–2.37), nausea or vomiting ( OR 1.64; 95% CI , 1.48–1.82) and shortness of breath ( OR 1.34; 95% CI , 1.21–1.48). Women had lower odds of presenting with chest pain ( OR 0.70; 95% CI , 0.63–0.78) and diaphoresis (OR 0.84; 95% CI , 0.76–0.94). Both sexes presented most often with chest pain (pooled prevalences, men 79%; 95% CI , 72–85, pooled prevalences, women 74%; 95% CI , 72–85). Other symptoms also showed substantial overlap in prevalence. The presence of sex differences has been established since the early 2000s. Newer studies did not materially change cumulative findings. Conclusions Women with ACS do have different symptoms at presentation than men with ACS , but there is also considerable overlap. Since these differences have been shown for years, symptoms should no longer be labeled as “atypical” or “typical.”

IntroductionCardiovascular disease and diabetes have shown to be predictive of clinical deterioration towards critical illness or death in the hospitalised COVID-19 patient population. The aim of this study was to determine the incremental value of cardiovascular vulnerability - defined by the number of cardiovascular diseases and/or diabetes - in predicting the risk of escalation of care towards hospital referral in primary care patients with clinically suspected or confirmed COVID-19. MethodsData were retrospectively collected from three large Dutch primary care registries with routine care data of {+/-}850,000 people. A prognostic prediction model was developed in two databases to assess the incremental value of cardiovascular vulnerability. Data from the first wave of COVID-19 infections in the Netherlands (March 1 2020 to June 1 2020) was used for derivation. A multivariable logistic regression model was fitted to predict hospital referral within 90 days follow-up after first consultation in consecutive adult patients seen in primary care for COVID-19 symptoms. Age, sex, the interaction between age and sex, and the number of underlying cardiovascular diseases and/or diabetes (0, 1, or [≥]2) were pre-specified as predictors prior to the analyses. The model was (i) compared to a simpler model without the predictor number of cardiovascular diseases and/or diabetes and (ii) externally validated in COVID-19 confirmed patients during the second wave (June 1 2020 to April 15 2021) in all three databases. ResultsThere were 5,475 patients included for model development and 6.8% had the primary outcome hospital referral. The model with number of cardiovascular diseases included as a predictor performed better than a model without this predictor (likelihood ratio test p

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.

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.

There is an unmet need for effective treatment strategies to reduce morbidity and mortality in patients with heart failure with preserved ejection fraction (HFpEF). Until recently, attention in patients with HFpEF was almost exclusively focused on the left side. However, it is now increasingly recognized that right heart dysfunction is common and contributes importantly to poor prognosis in HFpEF. More insights into the development of right heart dysfunction in HFpEF may aid to our knowledge about this complex disease and may eventually lead to better treatments to improve outcomes in these patients. In this position paper from the Heart Failure Association of the European Society of Cardiology, the Committee on Heart Failure with Preserved Ejection Fraction reviews the prevalence, diagnosis, and pathophysiology of right heart dysfunction and failure in patients with HFpEF. Finally, potential treatment strategies, important knowledge gaps and future directions regarding the right side in HFpEF are discussed.

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.

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.

Background To assess the trend in age- and sex-stratified mortality after hospitalization for heart failure (HF) in the Netherlands. Methods Two nationwide cohorts of patients, hospitalized for new onset heart failure between 01.01.2000–31.12.2002 and between 01.01.2008–31.12.2010, were constructed by linkage of the Dutch Hospital Discharge Registry and the National Cause of Death registry. 30-day, 1-year and 5 -year overall and cause-specific mortality rates stratified by age and sex were assessed and compared over time. Results We identified 40,230 men and 41,582 women. In both cohorts, men were on average younger than women (74–75 and 78–79 years, respectively) and more often had comorbid conditions (37 and 30%, respectively). In the 2008–10 cohort, mortality rates for men were 13, 32 and 64% for respectively 30-day, 1-year and 5-year mortality and 14, 33 and 66% for women. Mortality rates increased considerably with age similarly in men and women (e.g. from 10.5% in women aged 25–54 to 46.1% in those aged 85 and older after 1 year). Between the two time periods, mortality rates dropped across all ages, equally strong in women as in men. The 1-year absolute risk of death declined by 4.0% (from 36.1 to 32.1%) in men and 3.2% (from 36.2 to 33.0%) in women. Conclusions Mortality after hospitalization for new onset HF remains high, however, both short-term and long-term survival is improving over time. This improvement was similar across all ages and equally strong in women as in men.

The Heart Failure Association of the European Society of Cardiology has published a previous position paper and various guidelines over the past decade recognizing the value of palliative care for those affected by this burdensome condition. Integrating palliative care into evidence-based heart failure management remains challenging for many professionals, as it includes the identification of palliative care needs, symptom control, adjustment of drug and device therapy, advance care planning, family and informal caregiver support, and trying to ensure a good death. This new position paper aims to provide day-to-day practical clinical guidance on these topics, supporting the coordinated provision of palliation strategies as goals of care fluctuate along the heart failure disease trajectory. The specific components of palliative care for symptom alleviation, spiritual and psychosocial support, and the appropriate modification of guideline-directed treatment protocols, including drug deprescription and device deactivation, are described for the chronic, crisis and terminal phases of heart failure. Funding Agencies|Patient Forum of the European Society of Cardiology

In recent decades, cardiovascular mortality has reduced significantly. Among others, improved treatment options for cardiovascular disease (CVD) and a reduction of smoking since the 1960s have contributed to this decline.1 In many countries, smoking in public areas is prohibited. However, western dietary habits, including foods high in sugar, salt and fat, and lack of exercise are still persistent, leading to obesity, diabetes and hypertension. Yet, despite numerous guidelines on prevention and treatment of CVD with medication and lifestyle management, the incidence of CVD is still increasing in many countries, fuelled by rising obesity levels, sedentary lifestyles and increased longevity.2 In particular in the southern hemisphere CVD is on the increase, with high rates of obesity, diabetes and hypertension.3 Demographics are changing in low and middle income countries, fuelling the rise of chronic diseases and a persistent burden of infectious diseases overwhelming the limited health care resources.4 In western countries survival after CVD events has successfully improved; however, at the price of more patients living with chronic CVDs.5 These developments will lead to an increased demand on healthcare services now and in the years ahead for both the prevention and the management of CVD. The organisation and continuity of care through the various layers of the different national healthcare systems is challenging and calls for close collaboration between hospital specialists, general practitioners (GPs) and other primary care workers in the battle against CVD. GPs are key in identifying patients at risk of CVD and providing individualised, risk stratified preventive care

Contains fulltext : 225355.pdf (Publisher’s version ) (Open Access) In recent years, as more and more experience has been gained with prescribing direct oral anticoagulants (DOACs), new research initiatives have emerged in the Netherlands to improve the safety and appropriateness of DOAC treatment for stroke prevention in patients with atrial fibrillation (AF). These initiatives address several contemporary unresolved issues, such as inappropriate dosing, non-adherence and the long-term management of DOAC treatment. Dutch initiatives have also contributed to the development and improvement of risk prediction models. Although fewer bleeding complications (notably intracranial bleeding) are in general seen with DOACs in comparison with vitamin K antagonists, to successfully identify patients with high bleeding risk and to tailor anticoagulant treatment accordingly to mitigate this increased bleeding risk, is one of the research aims of recent and future years. This review highlights contributions from the Netherlands that aim to address these unresolved issues regarding the anticoagulant management in AF in daily practice, and provides a narrative overview of contemporary stroke and bleeding risk assessment strategies.

Aims Early age at menarche has been reported to be associated with increased risks of developing type 2 diabetes (T2D) and coronary heart disease (CHD) in adulthood, but a late menarche has also been found to be associated with an increased risk of CHD. Both T2D and CHD are important risk factors for developing heart failure (HF). We examined the relationship between age at menarche (AAM) and HF incidence in women from the European Prospective Investigation into Cancer and Nutrition – Netherlands (EPIC-NL) cohort study. Methods and results The EPIC-NL cohort comprised 28,504 women aged 20–70 years at baseline (1993–1997). Mean age at menarche was 13.3 (standard deviation 1.6) years. During a median follow-up of 15.2 years HF occurred in 631 women. Cox proportional hazard regression models, stratified by cohort and adjusted for potential confounders, were used to investigate the associations between AAM and HF incidence. After confounder adjustment, each year of older age at menarche was associated with a 5% lower risk of HF (hazard ratio 0.95 (95% CI, 0.91–1.00), p-value 0.048). Further adjusting for body mass index (BMI), prevalent CHD, hypertension, or prevalent T2D as potential mediators between early menarche and risk of HF attenuated the associations between AAM and risk of HF to non-significance. Conclusion Older AAM reduced the risk of HF in this study. BMI, prevalent CHD, hypertension and prevalent T2D seemed to mediate this association. Future research with a longer follow-up should establish whether there is an independent effect of AAM on HF risk. Also, further phenotyping of HF cases is necessary to enable whether the associations differ for the various subtypes of HF.

IntroductionCombined with patient history and physical examination, a negative D-dimer can safely rule-out pulmonary embolism (PE). However, the D-dimer test is frequently false positive, leading to many (with hindsight) ‘unneeded’ referrals to secondary care. Recently, the novel YEARS algorithm, incorporating flexible D-dimer thresholds depending on pretest risk, was developed and validated, showing its ability to safely exclude PE in the hospital environment. Importantly, this was accompanied with 14% fewer computed tomographic pulmonary angiography than the standard, fixed D-dimer threshold. Although promising, in primary care this algorithm has not been validated yet.Methods and analysisThe PECAN (DiagnosingPulmonaryEmbolism in the context ofCommonAlternative diagNoses in primary care) study is a prospective diagnostic study performed in Dutch primary care. Included patients with suspected acute PE will be managed by their general practitioner according to the YEARS diagnostic algorithm and followed up in primary care for 3 months to establish the final diagnosis. To study the impact of the use of the YEARS algorithm, the primary endpoints are the safety and efficiency of the YEARS algorithm in primary care. Safety is defined as the proportion of false-negative test results in those not referred. Efficiency denotes the proportion of patients classified in this non-referred category. Additionally, we quantify whether C reactive protein measurement has added diagnostic value to the YEARS algorithm, using multivariable logistic and polytomous regression modelling. Furthermore, we will investigate which factors contribute to the subjective YEARS item ‘PE most likely diagnosis’.Ethics and disseminationThe study protocol was approved by the Medical Ethical Committee Utrecht, the Netherlands. Patients eligible for inclusion will be asked for their consent. Results will be disseminated by publication in peer-reviewed journals and presented at (inter)national meetings and congresses.Trial registrationNTR 7431.

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.

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 Access to echocardiography in primary care is limited, but is necessary to accurately diagnose heart failure (HF). Aim To determine the proportion of patients with a GP’s diagnosis of HF who really have HF. Design and setting A cross-sectional study of patients in 30 general practices with a GP’s diagnosis of heart failure, based on the International Classification of Primary Care (ICPC) code K77, between June and November 2011. Method Electronic medical records of the patients’ GPs were scrutinised for information on the diagnosis. An expert panel consisting of two cardiologists and an experienced GP used all available diagnostic information, and established the presence or absence of HF according to the criteria of the European Society of Cardiology (ESC) HF guidelines. Results In total, 683 individuals had a GP’s diagnosis of HF. The mean age was 77.9 (SD 11.4) years, and 42.2% were male. Of these 683, 79.6% received cooperative care from a cardiologist. In 73.5% of cases, echocardiography was available for panel re-evaluation. Based on consensus opinion of the panel, 434 patients (63.5%, 95% confidence interval [CI] = 59.9 to 67.1) had definite HF, of which 222 (32.5%, 95% CI = 30.9 to 34.1) had HF with a reduced ejection fraction (HFrEF), 207 (30.3%, 95% CI = 29.0 to 31.6) had HF with a preserved ejection fraction (HFpEF), and five (0.7%, 95% CI = 1.2 to 2.6) had isolated right-sided HF. In 17.3% of cases (95% CI = 14.4 to 20.0), the panel considered HF absent, and in 19.2% (95% CI = 16.3 to 22.2) the diagnosis remained uncertain. Conclusion More than one-third of primary care patients labelled with HF may not have HF, and such overdiagnosis may result in inadequate patient management.