Quality of heart failure registration in primary care: observations from 1 million electronic health records in the Amsterdam Metropolitan Area.

OBJECTIVES: Proper coding of heart failure (HF) in electronic health records (EHRs) is an important prerequisite for adequate care and research towards this vulnerable patient population. We set out to evaluate the accuracy of registration of HF diagnoses in primary care EHRs. METHODS: In a routine primary care database covering the Amsterdam Metropolitan Area, we identified all episodes of care with International Classification of Primary Care (ICPC) codes K77 (decompensatio cordis) or K84.03 (cardiomyopathy) up to 31/12/2021. We also performed two text-based searches to identify HF episodes without an appropriate ICPC-code. An expert panel evaluated all ICPC and text matches for congruence between the assigned codes and notes. RESULTS: From a database of 968,433 records we identified 19,106 patients (2.0 %) with a total of 24,011 ICPC-coded HF episodes. Removal of 1,324 episodes found to concern other or uncertain diagnoses and inclusion of 4,582 validated HF episodes identified through text search led to exclusion of 909 (overregistration: 4.8 %) and inclusion of 2,266 additional patients (underregistration: 11.1 %). The inclusion of miscoded HF episodes advanced the first known date of HF diagnosis in 3.9 % of records, with a median shift of 3.45 years. Episode-level underregistration decreased significantly over time, from 23.8 % in 2006 to 10.0 % in 2021. CONCLUSIONS: While there is improvement over time, there are still substantial levels of over- and underregistration of HF, emphasizing the need for cautious interpretation of ICPC-coded data. The findings contribute to the understanding of HF registration issues in primary care and provide insights for improving registration practices.

Evaluation of the introduction of a single-lead ECG device and digital cardiologist consultation platform among general practitioners in the Netherlands.

AIM: To evaluate the use of a single-lead electrocardiography (1L-ECG) device and digital cardiologist consultation platform in diagnosing arrhythmias among general practitioners (GPs). BACKGROUND: Handheld 1L-ECG offers a user-friendly alternative to conventional 12-lead ECG in primary care. While GPs can safely rule out arrhythmias on 1L-ECG recordings, expert consultation is required to confirm suspected arrhythmias. Little is known about GPs' experiences with both a 1L-ECG device and digital consultation platform for daily practice. METHODS: We used two distinct methods in this study. First, in an observational study, we collected and described all cases shared by GPs within a digital cardiologist consultation platform initiated by a local GP cooperative. This GP cooperative distributed KardiaMobile 1L-ECG devices among all affiliated GPs (n = 203) and invited them to this consultation platform. In the second part, we used an online questionnaire to evaluate the experiences of these GPs using the KardiaMobile and consultation platform. FINDINGS: In total, 98 (48%) GPs participated in this project, of whom 48 (49%) shared 156 cases. The expert panel was able to provide a definitive rhythm interpretation in 130 (83.3%) shared cases and answered in a median of 4 min (IQR: 2-18). GPs responding to the questionnaire (n = 43; 44%) thought the KardiaMobile was of added value for rhythm diagnostics in primary care (n = 42; 98%) and easy to use (n = 41; 95%). Most GPs (n = 36; 84%) valued the feedback from the cardiologists in the consultation platform. GPs experienced this project to have a positive impact on both the quality of care and diagnostic efficiency for patients with (suspected) cardiac arrhythmias. Although we lack a comprehensive picture of experienced impediments by GPs, solving technical issues was mentioned to be helpful for further implementation. More research is needed to explore reasons of GPs not motivated using these tools and to assess real-life clinical impact.

Troponin testing in routine primary care: observations from a dynamic cohort study in the Amsterdam metropolitan area.

OBJECTIVES: Troponin testing is indicated in the diagnostic work-up of acute coronary syndrome (ACS) and incorporated in risk stratification pathways. This study aims to gain insights on the use, outcomes, and diagnostic accuracy of troponin testing in routine primary care; a setting that is understudied. METHODS: Routine data were used from the academic primary care network in the Amsterdam metropolitan area (968,433 patient records). The study population included adult patients who underwent high-sensitivity troponin I or T (hs-TnI/T) testing between 2011 and 2021. The primary outcome was the reported diagnosis and the secondary outcome was the diagnostic accuracy measured by death or ACS at 30 days. RESULTS: 3,184 patients underwent hs-troponin testing, either with hsTNT (n=2,333) or hsTNI (n=851). Median patients' age was 55 (44-65) years, and 62.3 % were female. Predominant symptoms were chest pain and dyspnea (56.7 %). Additional diagnostic laboratory tests were commonly performed (CRP: 47.7 %, natriuretic peptides: 25.6 %, d-dimer: 21.5 %). Most common diagnoses were musculoskeletal symptoms (21.6 %) and coronary heart disease (7.1 %; 1.1 % ACS). Troponin testing showed sensitivity and specificity of 77.8 % (60.9-89.9) and 94.3 % (93.5-95.1), respectively. Negative and positive predictive values were 99.7 (99.5-99.9) and 13.5 (11.1-16.4), and positive and negative likelihood ratios were 13.7 (10.9-17.1) and 0.24 (0.13-0.43). CONCLUSIONS: GPs occasionally use troponin testing in very low-risk patients, often as part of a multi-marker rule-out strategy. The diagnostic characteristics of troponin tests, while promising, warrant prospective validation and implementation to facilitate appropriate use.

Diagnostic properties of natriuretic peptides and opportunities for personalized thresholds for detecting heart failure in primary care.

OBJECTIVES: Heart failure (HF) is a prevalent syndrome with considerable disease burden, healthcare utilization and costs. Timely diagnosis is essential to improve outcomes. This study aimed to compare the diagnostic performance of B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) in detecting HF in primary care. Our second aim was to explore if personalized thresholds (using age, sex, or other readily available parameters) would further improve diagnostic accuracy over universal thresholds. METHODS: A retrospective study was performed among patients without prior HF who underwent natriuretic peptide (NP) testing in the Amsterdam General Practice Network between January 2011 and December 2021. HF incidence was based on registration out to 90 days after NP testing. Diagnostic accuracy was evaluated with AUROC, sensitivity and specificity based on guideline-recommended thresholds (125 ng/L for NT-proBNP and 35 ng/L for BNP). We used inverse probability of treatment weighting to adjust for confounding. RESULTS: A total of 15,234 patients underwent NP testing, 6,870 with BNP (4.5 % had HF), and 8,364 with NT-proBNP (5.7 % had HF). NT-proBNP was more accurate than BNP, with an AUROC of 89.9 % (95 % CI: 88.4-91.2) vs. 85.9 % (95 % CI 83.5-88.2), with higher sensitivity (95.3 vs. 89.7 %) and specificity (59.1 vs. 58.0 %). Differentiating NP cut-off by clinical variables modestly improved diagnostic accuracy for BNP and NT-proBNP compared with a universal threshold. CONCLUSIONS: NT-proBNP outperforms BNP for detecting HF in primary care. Personalized instead of universal diagnostic thresholds led to modest improvement.

Enoxaparin for symptomatic COVID-19 managed in the ambulatory setting: An individual patient level analysis of the OVID and ETHIC trials.

BACKGROUND: Antithrombotic treatment may improve the disease course in non-critically ill, symptomatic COVID-19 outpatients. METHODS: We performed an individual patient-level analysis of the OVID and ETHIC randomized controlled trials, which compared enoxaparin thromboprophylaxis for either 14 (OVID) or 21 days (ETHIC) vs. no thromboprophylaxis for outpatients with symptomatic COVID-19 and at least one additional risk factor. The primary efficacy outcome included all-cause hospitalization and all-cause death within 30 days from randomization. Both studies were prematurely stopped for futility. Secondary efficacy outcomes were major symptomatic venous thromboembolic events, arterial cardiovascular events, or their composite occurring within 30 days from randomization. The same outcomes were assessed over a 90-day follow-up. The primary safety outcome was major bleeding (ISTH criteria). RESULTS: A total of 691 patients were randomized: 339 to receive enoxaparin and 352 to the control group. Over 30-day follow-up, the primary efficacy outcome occurred in 6.0 % of patients in the enoxaparin group vs. 5.8 % of controls for a risk ratio (RR) of 1.05 (95%CI 0.57-1.92). The incidence of major symptomatic venous thromboembolic events and arterial cardiovascular events was 0.9 % vs. 1.8 %, respectively (RR 0.52; 95%CI 0.13-2.06). Most cardiovascular thromboembolic events were represented by symptomatic venous thromboembolic events, occurring in 0.6 % vs. 1.5 % of patients, respectively. A similar distribution of outcomes between the treatment groups was observed over 90 days. No major bleeding occurred in the enoxaparin group vs. one (0.3 %) in the control group. CONCLUSIONS: We found no evidence for the clinical benefit of early administration of enoxaparin thromboprophylaxis in outpatients with symptomatic COVID-19. These results should be interpreted taking into consideration the relatively low occurrence of events.

Characteristics of heart failure in the Amsterdam metropolitan area (AMSTERDAM-HF): Data from a dynamic general practice cohort (2011-2021).

BACKGROUND: Heart failure (HF) is a common cardiac syndrome with a high disease burden and poor prognosis in our aging populations. Understanding the characteristics of patients with newly diagnosed HF is essential for improving care and outcomes. The AMSTERDAM-HF study is aimed to examine the population characteristics of patients with incident HF. METHODS: We performed a retrospective dynamic cohort study in the Amsterdam general practice network consisting of 904,557 individuals. Incidence HF rates, geographical demographics, patient characteristics, risk factors, symptoms prior to HF diagnosis, and prognosis were reported. RESULTS: The study identified 10,067 new cases of HF over 6,816,099 person-years. The median age of patients was 77 years (25th-75th percentile: 66-85), and 48% were male. The incidence rate of HF was 213.44 per 100,000 patient-years, and was higher in male versus female patients (incidence rate ratio: 1.08, 95%-CI:1.04-1.13). Hypertension (men 46.3% and women 55.8%), coronary artery disease (men 36% and women 25%) and diabetes mellitus (men 30.5% and women 26.8%) were the most common risk factors. Dyspnoea and oedema were key reported symptoms prior to HF diagnosis. Survival rates at 10-year follow-up were poor, particularly in men (36.4%) compared to women (39.7%). Incidence rates, comorbidity burden and prognosis were worse in city districts with high ethnic diversity and low socio-economic position. CONCLUSION: Our study provides insights into incident HF in a contemporary Western European, multi-ethnic, urban population. It highlights notable sex, age, and geographical differences in incidence rates, risk factors, symptoms and prognosis.

Diagnostic accuracy of the PMcardio smartphone application for artificial intelligence-based interpretation of electrocardiograms in primary care (AMSTELHEART-1).

Background: The use of 12-lead electrocardiogram (ECG) is common in routine primary care, however it can be difficult for less experienced ECG readers to adequately interpret the ECG. Objective: To validate a smartphone application (PMcardio) as a stand-alone interpretation tool for 12-lead ECG in primary care. Methods: We recruited consecutive patients who underwent 12-lead ECG as part of routinely indicated primary care in the Netherlands. All ECGs were assessed by the PMcardio app, which analyzes a photographed image of 12-lead ECG for automated interpretation, installed on an Android platform (Samsung Galaxy M31) and an iOS platform (iPhone SE2020). We validated the PMcardio app for detecting any major ECG abnormality (MEA, primary outcome), defined as atrial fibrillation/flutter (AF), markers of (past) myocardial ischemia, or clinically relevant impulse and/or conduction abnormalities; or AF (key secondary outcome) with a blinded expert panel as reference standard. Results: We included 290 patients from 11 Dutch general practices with median age 67 (interquartile range 55-74) years; 48% were female. On reference ECG, 71 patients (25%) had MEA and 35 (12%) had AF. Sensitivity and specificity of PMcardio for MEA were 86% (95% CI: 76%-93%) and 92% (95% CI: 87%-95%), respectively. For AF, sensitivity and specificity were 97% (95% CI: 85%-100%) and 99% (95% CI: 97%-100%), respectively. Performance was comparable between Android and iOS platform (kappa = 0.95, 95% CI: 0.91-0.99 and kappa = 1.00, 95% CI: 1.00-1.00 for MEA and AF, respectively). Conclusion: A smartphone app developed to interpret 12-lead ECGs was found to have good diagnostic accuracy in a primary care setting for major ECG abnormalities, and near-perfect properties for diagnosing AF.

Longitudinal association of premature atrial contractions with atrial fibrillation and brain ischemia in people with type 2 diabetes: The Hoorn Diabetes Care System cohort.

Background: Premature atrial contractions (PACs) are potential markers for imminent onset of both atrial fibrillation (AF) and brain ischemia (BI; transient ischemic attack [TIA] or ischemic stroke). We investigated the association of PACs with incident AF and BI events separately, and of incident AF with BI events in people with type 2 diabetes (T2D) without pre-existing AF or cerebrovascular disease. Methods: A prospective longitudinal study of 12,242 people with T2D without known AF or cerebrovascular disease from the Hoorn Diabetes Care System cohort. Annual measurements (1998-2018) included cardiovascular risk factors, over 85,000 ECGs, and self-reported cardiovascular events. We assessed the association of PACs with incident AF and BI events and of incident AF with BI events using time-dependent Cox-regression models, adjusted for time-varying cardiovascular risk factors and medication use (Hazard Ratios with 95%CIs). Results: The baseline mean age was 62.2 ± 11.9 years. During a median follow-up of 7.0 (IQR 3.4-11.0) years, 1031 (8.4 %) participants had PACs, and 566 (4.6 %) had incident AF at any of the median 6 (IQR 3-10) annual ECG recordings. BI events occurred in 517 (4.2 %) people (304 TIAs, 213 ischemic strokes). After adjustment, PACs were associated with incident AF (Hazard Ratio, 1.96 (95%CI, 1.53-2.50)), but not with overall BI events (1.09 (0.76-1.56)), or with TIA (0.91 (0.57-1.46)) or ischemic stroke (1.50 (0.88-2.54)) separately. AF was not associated with BI events (0.95 (0.55-1.63)). Conclusions: In people with T2D without a history of AF or BI events, PACs are associated with a two-fold increased risk of incident AF.

Personalized approach using wearable technology for early detection of atrial fibrillation in high-risk primary care patients (PATCH-AF): Study protocol for a cluster randomized controlled trial.

BACKGROUND: Atrial fibrillation (AF) is a common cardiac arrhythmia with a lifetime risk of one in 4. Unfortunately, AF often remains undetected, particularly when it is paroxysmal, for which single time-point evaluation is less effective. Recently, unobtrusive cardiac arrhythmia monitoring devices have become available, providing the opportunity to conduct prolonged electrocardiographic (ECG) monitoring in a patient-friendly manner. We hypothesize that applying these devices in at risk patients may improve AF detection, particularly when used during repeated episodes. We therefore aim to evaluate the diagnostic yield of yearly screening for atrial fibrillation when using a wearable device for continuous ECG monitoring for 7 days in primary care patients ≥ 65 years deemed at high-risk of AF (CHA2DS2VASc score ≥3 for men or ≥4 for women) compared with usual care over a study period of 3 years. METHODS: Primary care based, cluster-randomized controlled trial with 10 general practices randomized to the intervention group and 10 general practices randomized to control group. In each group, we aim to enroll 930 patients, ≥65 years and a CHA2DS2VASc score ≥3 for men or ≥ 4 for women. The intervention consists of continuous ECG monitoring for 7 days at start of the study (t = 0), after one (t = 1) and 2 years (t = 2). The control practices will follow usual diagnostic care procedures. RESULTS: Results are expected in 2025. CONCLUSIONS: This study differs from previous randomized controlled trials, as it involves longitudinal screening of a risk-stratified population. In case of a beneficial diagnostic yield, the PATCH-AF study will add to the evidence for AF screening. TRIAL REGISTRATION: The PATCH-AF study is registered at The Netherlands Trial Register (NTR number NL9656).

Thromboprophylactic low-molecular-weight heparin versus standard of care in unvaccinated, at-risk outpatients with COVID-19 (ETHIC): an open-label, multicentre, randomised, controlled, phase 3b trial.

BACKGROUND: COVID-19 is associated with inflammation and an increased risk of thromboembolic complications. Prophylactic doses of low-molecular-weight heparin have been used in hospitalised and non-critically ill patients with COVID-19. We aimed to evaluate the efficacy and safety of prophylactic low-molecular-weight heparin (enoxaparin) versus standard of care (no enoxaparin) in at-risk outpatients with COVID-19. METHODS: This open-label, multicentre, randomised, controlled, phase 3b trial (ETHIC) was done at 15 centres in six countries (Belgium, Brazil, India, South Africa, Spain, and the UK). We consecutively enrolled participants aged at least 30 years who had not received a COVID-19 vaccine and had symptomatic, confirmed COVID-19 in the outpatient setting plus at least one risk factor for severe disease. Within 9 days of symptom onset and by use of a web-based random block design (block size either 2 or 4), eligible participants were randomly assigned (1:1) to receive either subcutaneous enoxaparin for 21 days (40 mg once daily if they weighed <100 kg and 40 mg twice daily if they weighed ≥100 kg) or standard of care (without enoxaparin). The primary efficacy endpoint was the composite of all-cause hospitalisation and all-cause mortality at 21 days after randomisation and, in our main analysis, was analysed in the intention-to-treat population, which comprised all patients who were randomly assigned. Safety was also analysed in the intention-to-treat population for our main analysis. This trial is registered with ClinicalTrials.gov, NCT04492254, and is complete. FINDINGS: Following the advice of the Data and Safety Monitoring Board, this study was terminated early due to slow enrolment and a lower-than-expected event rate. Between Oct 27, 2020, and Nov 8, 2021, 230 patients with COVID-19 were assessed for eligibility, of whom 219 were enrolled and randomly assigned to receive standard of care (n=114) or enoxaparin (n=105). 96 (44%) patients were women, 122 (56%) were men, and one patient had missing sex data. 141 (65%) of 218 participants with data on race and ethnicity were White, 60 (28%) were Asian, and 16 (7%) were Black, mixed race, or Arab or Middle Eastern. Median follow-up in both groups was 21 days (IQR 21-21). There was no difference in the composite of all-cause mortality and hospitalisation at 21 days between the enoxaparin group (12 [11%] of 105 patients) and the standard-of-care group (12 [11%] of 114 patients; unadjusted hazard ratio 1·09 [95% CI 0·49-2·43]; log-rank p=0·83). At 21 days, two (2%) of 105 patients in the enoxaparin group (one minor bleed and one bleed of unknown severity) and one (1%) of 114 patients in the standard-of-care group (major abnormal uterine bleeding) had a bleeding event. 22 (21%) patients in the enoxaparin group and 13 (11%) patients in the standard-of-care group had adverse events. The most common adverse event in both groups was COVID-19-related pneumonia (six [6%] patients in the enoxaparin group and five [4%] patients in the standard-of-care group). One patient in the enoxaparin group died and their cause of death was unknown. INTERPRETATION: The ETHIC trial results suggest that prophylaxis with low-molecular-weight heparin had no benefit for at-risk outpatients with COVID-19. Although the trial was terminated early, our data, combined with data from similar studies, provide further insights to inform international guidelines and influence clinical practice. FUNDING: The Thrombosis Research Institute and Sanofi UK.

Validating risk models versus age alone for atrial fibrillation in a young Dutch population cohort: should atrial fibrillation risk prediction be expanded to younger community members?

BACKGROUND: Advancing age is the primary selection criterion for community screening for atrial fibrillation (AF), with selection often restricted to those aged ≥65 years. If multivariable models were shown to have considerable additional value over age alone in predicting AF risk among younger individuals, AF screening could be expanded to patients with lower age, but with high AF risk as per a validated risk model. METHODS: We validated risk models CHARGE-AF (Cohorts for Heart and Aging Research in Genomic Epidemiology model for AF) and FHS-AF (Framingham Heart Study model for AF), and risk scores CHA2DS2-VASc and CHA2DS2-VA, and presented their predictive abilities for 5-year and 10-year AF risk versus that of age alone in a young Dutch population cohort (PREVEND) free from AF at baseline. We assessed discrimination by the C-statistic and calibration by the calibration plot and stratified Kaplan-Meier plot using survey-weighted Cox models. RESULTS: During 5-year and 10-year follow-up there were n=98 (2.46/1000 person-years) and n=249 (3.29/1000 person-years) new AF cases, respectively, among 8265 participants with mean age 49±13 years. CHARGE-AF and FHS-AF both showed good discrimination for 5-year and 10-year AF (C-statistic range 0.83-0.86) with accurate calibration for 5-year AF, but overestimation of 10-year AF risk in highest-risk individuals. CHA2DS2-VASc and CHA2DS2-VA relatively underperformed. Age alone showed similar discrimination to that of CHARGE-AF and FHS-AF both in the overall, young PREVEND cohort and in subgroups for lower age and lower stroke risk. CONCLUSION: Multivariable models accurately discriminate for 5-year and 10-year AF risk among young European community-dwelling individuals. However, their additional discriminatory value over age alone was limited. Selection strategies for primary AF screening using multivariable models should not be expanded to younger individuals.

Risk of stroke and bleeding in relation to hypertension in anticoagulated patients with atrial fibrillation: a meta-analysis of randomised controlled trials.

BACKGROUND AND PURPOSE: Hypertension is common in patients with atrial fibrillation (AF) and carries an additional risk for complications, most notably stroke and bleeding. We assessed the history of hypertension, level of blood pressure control, and an interaction with the choice of oral anticoagulants on clinical outcomes. METHODS: We performed a systematic review and meta-analysis of studies that randomised patients to novel oral anticoagulants (NOACs) or vitamin K antagonists (VKAs) and reported outcomes stratified by presence of hypertension. Collected outcomes were: ischaemic stroke or systemic embolism (SE), haemorrhagic stroke, intracranial haemorrhage and major bleeding. Log adjusted hazard ratios (HR) and corresponding standard error were calculated, and HRs were compared using Mantel-Haenszel random effects. Quality of the evidence was assessed with Cochrane risk of bias tool. RESULTS: Five high-quality studies were eligible, including 71.527 participants who received NOACs (apixaban, dabigatran, edoxaban, rivaroxaban) or VKAs, with median follow-up of 1.8-2.8 years. Compared with patients without hypertension, those with hypertension had higher adjusted risk for ischaemic stroke/SE (HR: 1.25, 95%-CI:1.09, 1.43) and haemorrhagic stroke (HR:1.98, 1.24-3.16). On a continuous scale, the risk of ischaemic stroke/SE increased 6-7% per 10 mmHg increase in systolic blood pressure. No interactions were found between the efficacy or safety of NOACs versus VKAs in the presence or absence of hypertension. In both groups, the use of NOACs led to a lower risk of ischaemic stroke/SE, haemorrhagic stroke and intracranial haemorrhage compared with patients that used VKAs. CONCLUSIONS: Adequate blood pressure management is vital to optimally reduce the risk of stroke in patients with atrial fibrillation. The benefits of NOACs over VKAs, also apply to patients with elevated blood pressure.

Manual QT interval measurement with a smartphone-operated single-lead ECG versus 12-lead ECG: a within-patient diagnostic validation study in primary care.

OBJECTIVE: To determine the accuracy of QT measurement in a smartphone-operated, single-lead ECG (1L-ECG) device (AliveCor KardiaMobile 1L). DESIGN: Cross-sectional, within-patient diagnostic validation study. SETTING/PARTICIPANTS: Patients underwent a 12-lead ECG (12L-ECG) for any non-acute indication in primary care, April 2017-July 2018. INTERVENTION: Simultaneous recording of 1L-ECGs and 12L-ECGs with blinded manual QT assessment. OUTCOMES OF INTEREST: (1) Difference in QT interval in milliseconds (ms) between the devices; (2) measurement agreement between the devices (excellent agreement <20 ms and clinically acceptable agreement <40 ms absolute difference); (3) sensitivity and specificity for detection of extreme QTc (short (≤340 ms) or long (≥480 ms)), on 1L-ECGs versus 12L-ECGs as reference standard. In case of significant discrepancy between lead I/II of 12L-ECGs and 1L-ECGs, we developed a correction tool by adding the difference between QT measurements of 12L-ECG and 1L-ECGs. RESULTS: 250 ECGs of 125 patients were included. The mean QTc interval, using Bazett's formula (QTcB), was 393±25 ms (mean±SD) in 1L-ECGs and 392±27 ms in lead I of 12L-ECGs, a mean difference of 1±21 ms, which was not statistically different (paired t-test (p=0.51) and Bland Altman method (p=0.23)). In terms of agreement between 1L-ECGs and lead I, QTcB had excellent agreement in 66.9% and clinically acceptable agreement in 93.4% of observations. The sensitivity and specificity of detecting extreme QTc were 0% and 99.2%, respectively. The comparison of 1L-ECG QTcB with lead II of 12L-ECGs showed a significant difference (p=<0.01), but when using a correction factor (+9 ms) this difference was cancelled (paired t-test (p=0.43) or Bland Altman test (p=0.57)). Moreover, it led to improved rates of excellent (71.3%) and clinically acceptable (94.3%) agreement. CONCLUSION: Smartphone-operated 1L-ECGs can be used to accurately measure the QTc interval compared with simultaneously obtained 12L-ECGs in a primary care population. This may provide an opportunity for monitoring the effects of potential QTc-prolonging medications.

The Roth score as a triage tool for detecting hypoxaemia in general practice: a diagnostic validation study in patients with possible COVID-19.

AIM: To validate the Roth score as a triage tool for detecting hypoxaemia. BACKGROUNDS: The virtual assessment of patients has become increasingly important during the corona virus disease (COVID-19) pandemic, but has limitations as to the evaluation of deteriorating respiratory function. This study presents data on the validity of the Roth score as a triage tool for detecting hypoxaemia remotely in potential COVID-19 patients in general practice. METHODS: This cross-sectional validation study was conducted in Dutch general practice. Patients aged ≥18 with suspected or confirmed COVID-19 were asked to rapidly count from 1 to 30 in a single breath. The Roth score involves the highest number counted during exhalation (counting number) and the time taken to reach the maximal count (counting time).Outcome measures were (1) the correlation between both Roth score measurements and simultaneous pulse oximetry (SpO2) on room air and (2) discrimination (c-statistic), sensitivity, specificity and predictive values of the Roth score for detecting hypoxaemia (SpO2 < 95%). FINDINGS: A total of 33 physicians enrolled 105 patients (52.4% female, mean age of 52.6 ± 20.4 years). A positive correlation was found between counting number and SpO2 (rs = 0.44, P < 0.001), whereas only a weak correlation was found between counting time and SpO2 (rs = 0.15, P = 0.14). Discrimination for hypoxaemia was higher for counting number [c-statistic 0.91 (95% CI: 0.85-0.96)] than for counting time [c-statistic 0.77 (95% CI: 0.62-0.93)]. Optimal diagnostic performance was found at a counting number of 20, with a sensitivity of 93.3% (95% CI: 68.1-99.8) and a specificity of 77.8% (95% CI: 67.8-85.9). A counting time of 7 s showed the best sensitivity of 85.7% (95% CI: 57.2-98.2) and specificity of 81.1% (95% CI: 71.5-88.6). CONCLUSIONS: A Roth score, with an optimal counting number cut-off value of 20, maybe of added value for signalling hypoxaemia in general practice. Further external validation is warranted before recommending integration in telephone triage.

Screening for paroxysmal atrial fibrillation in primary care using Holter monitoring and intermittent, ambulatory single-lead electrocardiography.

BACKGROUND: Timely detection of atrial fibrillation (AF) is important because of its increased risk of thrombo-embolic events. Single time point screening interventions fall short in detection of paroxysmal AF, which requires prolonged electrocardiographic monitoring, usually using a Holter. However, traditional 24-48 h Holter monitoring is less appropriate for screening purposes because of its low diagnostic yield. Intermittent, ambulatory screening using a single-lead electrocardiogram (1 L-ECG) device can offer a more efficient alternative. METHODS: Primary care patients of ≥65 years participated in an opportunistic screening study for AF. We invited patients with a negative 12 L-ECG to wear a Holter monitor for two weeks and to use a MyDiagnostick 1 L-ECG device thrice daily. We report the yield of paroxysmal AF found by Holter monitoring and calculate the diagnostic accuracy of the 1 L-ECG device's built-in AF detection algorithm with the Holter monitor as reference standard. RESULTS: We included 270 patients, of whom four had AF in a median of 8.0 days of Holter monitoring, a diagnostic yield of 1.5% (95%-CI: 0.4-3.8%). In 205 patients we performed simultaneous 1 L-ECG screening. For diagnosing AF based on the 1 L-ECG device's AF detection algorithm, sensitivity was 66.7% (95%-CI: 9.4-99.2%), specificity 68.8% (95%-CI: 61.9-75.1%), positive predictive value 3.1% (95%-CI: 1.4-6.8%) and negative predictive value 99.3% (95%-CI: 96.6-99.9%). CONCLUSION: We found a low diagnostic yield of paroxysmal AF using Holter monitoring in elderly primary care patients with a negative 12 L-ECG. The diagnostic accuracy of an intermittently, ambulatory used MyDiagnostick 1 L-ECG device as interpreted by its built-in AF detection algorithm is limited.

Performance of popular pulse oximeters compared with simultaneous arterial oxygen saturation or clinical-grade pulse oximetry: a cross-sectional validation study in intensive care patients.

OBJECTIVES: To evaluate the performance of direct-to-consumer pulse oximeters under clinical conditions, with arterial blood gas measurement (SaO2) as reference standard. DESIGN: Cross-sectional, validation study. SETTING: Intensive care. PARTICIPANTS: Adult patients requiring SaO2-monitoring. INTERVENTIONS: The studied oximeters are top-selling in Europe/USA (AFAC FS10D, AGPTEK FS10C, ANAPULSE ANP 100, Cocobear, Contec CMS50D1, HYLOGY MD-H37, Mommed YM101, PRCMISEMED F4PRO, PULOX PO-200 and Zacurate Pro Series 500 DL). Directly after collection of a SaO2 blood sample, we obtained pulse oximeter readings (SpO2). SpO2-readings were performed in rotating order, blinded for SaO2 and completed <10 min after blood sample collection. OUTCOME MEASURES: Bias (SpO2-SaO2) mean, root mean square difference (ARMS), mean absolute error (MAE) and accuracy in identifying hypoxaemia (SaO2 ≤90%). As a clinical index test, we included a hospital-grade SpO2-monitor (Philips). RESULTS: In 35 consecutive patients, we obtained 2258 SpO2-readings and 234 SaO2-samples. Mean bias ranged from -0.6 to -4.8. None of the pulse oximeters met ARMS ≤3%, the requirement set by International Organisation for Standardisation (ISO)-standards and required for Food and Drug Administration (FDA) 501(k)-clearance. The MAE ranged from 2.3 to 5.1, and five out of ten pulse oximeters met the requirement of ≤3%. For hypoxaemia, negative predictive values were 98%-99%. Positive predictive values ranged from 11% to 30%. Highest accuracy (95% CI) was found for Contec CMS50D1; 91% (86-94) and Zacurate Pro Series 500 DL; 90% (85-94). The hospital-grade SpO2-monitor had an ARMS of 3.0% and MAE of 1.9, and an accuracy of 95% (91%-97%). CONCLUSION: Top-selling, direct-to-consumer pulse oximeters can accurately rule out hypoxaemia, but do not meet ISO-standards required for FDA-clearance.

Usefulness, pitfalls and interpretation of handheld single­lead electrocardiograms.

Single­lead electrocardiograms (1 L-ECGs) are increasingly used in (pre)clinical settings for the detection and monitoring of a range of rhythm and conduction disorders. In this short communication paper, we aim to provide an overview of the usefulness and potential pitfalls when implementing 1 L-ECGs into everyday clinical practice. Moreover, we provide recommendations for improving signal quality, as well as a systematic approach to the interpretation of 1 L-ECGs, which is somewhat different from standard 12­lead ECGs. Clinicians can use our illustrations and checklist as guidance when recording and interpreting 1 L-ECGs.

CHARGE-AF in a national routine primary care electronic health records database in the Netherlands: validation for 5-year risk of atrial fibrillation and implications for patient selection in atrial fibrillation screening.

AIMS: To validate a multivariable risk prediction model (Cohorts for Heart and Aging Research in Genomic Epidemiology model for atrial fibrillation (CHARGE-AF)) for 5-year risk of atrial fibrillation (AF) in routinely collected primary care data and to assess CHARGE-AF's potential for automated, low-cost selection of patients at high risk for AF based on routine primary care data. METHODS: We included patients aged ≥40 years, free of AF and with complete CHARGE-AF variables at baseline, 1 January 2014, in a representative, nationwide routine primary care database in the Netherlands (Nivel-PCD). We validated CHARGE-AF for 5-year observed AF incidence using the C-statistic for discrimination, and calibration plot and stratified Kaplan-Meier plot for calibration. We compared CHARGE-AF with other predictors and assessed implications of using different CHARGE-AF cut-offs to select high-risk patients. RESULTS: Among 111 475 patients free of AF and with complete CHARGE-AF variables at baseline (17.2% of all patients aged ≥40 years and free of AF), mean age was 65.5 years, and 53% were female. Complete CHARGE-AF cases were older and had higher AF incidence and cardiovascular comorbidity rate than incomplete cases. There were 5264 (4.7%) new AF cases during 5-year follow-up among complete cases. CHARGE-AF's C-statistic for new AF was 0.74 (95% CI 0.73 to 0.74). The calibration plot showed slight risk underestimation in low-risk deciles and overestimation of absolute AF risk in those with highest predicted risk. The Kaplan-Meier plot with categories <2.5%, 2.5%-5% and >5% predicted 5-year risk was highly accurate. CHARGE-AF outperformed CHA2DS2-VASc (Cardiac failure or dysfunction, Hypertension, Age >=75 [Doubled], Diabetes, Stroke [Doubled]-Vascular disease, Age 65-74, and Sex category [Female]) and age alone as predictors for AF. Dichotomisation at cut-offs of 2.5%, 5% and 10% baseline CHARGE-AF risk all showed merits for patient selection in AF screening efforts. CONCLUSION: In patients with complete baseline CHARGE-AF data through routine Dutch primary care, CHARGE-AF accurately assessed AF risk among older primary care patients, outperformed both CHA2DS2-VASc and age alone as predictors for AF and showed potential for automated, low-cost patient selection in AF screening.

Evaluation of general practitioners' single-lead electrocardiogram interpretation skills: a case-vignette study.

BACKGROUND: Handheld single-lead electrocardiograms (1L-ECG) present a welcome addition to the diagnostic arsenal of general practitioners (GPs). However, little is known about GPs' 1L-ECG interpretation skills, and thus its reliability in real-world practice. OBJECTIVE: To determine the diagnostic accuracy of GPs in diagnosing atrial fibrillation or flutter (AF/Afl) based on 1L-ECGs, with and without the aid of automatic algorithm interpretation, as well as other relevant ECG abnormalities. METHODS: We invited 2239 Dutch GPs for an online case-vignette study. GPs were asked to interpret four 1L-ECGs, randomly drawn from a pool of 80 case-vignettes. These vignettes were obtained from a primary care study that used smartphone-operated 1L-ECG recordings using the AliveCor KardiaMobile. Interpretation of all 1L-ECGs by a panel of cardiologists was used as reference standard. RESULTS: A total of 457 (20.4%) GPs responded and interpreted a total of 1613 1L-ECGs. Sensitivity and specificity for AF/Afl (prevalence 13%) were 92.5% (95% CI: 82.5-97.0%) and 89.8% (95% CI: 85.5-92.9%), respectively. PPV and NPV for AF/Afl were 45.7% (95% CI: 22.4-70.9%) and 98.8% (95% CI: 97.1-99.5%), respectively. GP interpretation skills did not improve in case-vignettes where the outcome of automatic AF-detection algorithm was provided. In detecting any relevant ECG abnormality (prevalence 22%), sensitivity, specificity, PPV and NPV were 96.3% (95% CI: 92.8-98.2%), 68.8% (95% CI: 62.4-74.6%), 43.9% (95% CI: 27.7-61.5%) and 97.9% (95% CI: 94.9-99.1%), respectively. CONCLUSIONS: GPs can safely rule out cardiac arrhythmias with 1L-ECGs. However, whenever an abnormality is suspected, confirmation by an expert-reader is warranted.

Rationale and design of a cohort study evaluating triage of acute chest pain in out-of-hours primary care in the Netherlands (TRACE).

The aims of this study are (1) to evaluate the performance of current triage for chest pain; (2) to describe the case mix of patients undergoing triage for chest pain; and (3) to identify opportunities to improve performance of current Dutch triage system for chest pain. Chest pain is a common symptom, and identifying patients with chest pain that require urgent care can be quite challenging. Making the correct assessment is even harder during telephone triage. Temporal trends show that the referral threshold has lowered over time, resulting in overcrowding of first responders and emergency services. While various stakeholders advocate for a more efficient triage system, careful evaluation of the performance of the current triage in primary care is lacking. TRiage of Acute Chest pain Evaluation in primary care (TRACE) is a large cohort study designed to describe the current Dutch triage system for chest pain and subsequently evaluate triage performance in regard to clinical outcomes. The study consists of consecutive patients who contacted the out-of-hours primary care facility with chest pain in the region of Alkmaar, the Netherlands, in 2017, with follow-up for clinical outcomes out to August 2019. The primary outcome of interest is 'major event', which is defined as the occurrence of death from any cause, acute coronary syndrome, urgent coronary revascularization, or other high-risk diagnoses in which delay is inadmissible and hospitalization is necessary. We will evaluate the performance of the triage system by assessing the ability of the triage system to correctly classify patients regarding urgency (accuracy), the proportion of safe actions following triage (safety) as well as rightfully deployed ambulances (efficacy). TRACE is designed to describe the current Dutch triage system for chest pain in primary care and to subsequently evaluate triage performance in regard to clinical outcomes.