The digital journey: 25 years of digital development in electrophysiology from an Europace perspective.

AIMS: Over the past 25 years there has been a substantial development in the field of digital electrophysiology (EP) and in parallel a substantial increase in publications on digital cardiology.In this celebratory paper, we provide an overview of the digital field by highlighting publications from the field focusing on the EP Europace journal. RESULTS: In this journey across the past quarter of a century we follow the development of digital tools commonly used in the clinic spanning from the initiation of digital clinics through the early days of telemonitoring, to wearables, mobile applications, and the use of fully virtual clinics. We then provide a chronicle of the field of artificial intelligence, a regulatory perspective, and at the end of our journey provide a future outlook for digital EP. CONCLUSION: Over the past 25 years Europace has published a substantial number of papers on digital EP, with a marked expansion in digital publications in recent years.

Systematic review finds risk of bias and applicability concerns for models predicting central line-associated bloodstream infection.

OBJECTIVES: To systematically review the risk of bias and applicability of published prediction models for risk of central line-associated bloodstream infection (CLA-BSI) in hospitalized patients. STUDY DESIGN AND SETTING: Systematic review of literature in PubMed, Embase, Web of Science Core Collection, and Scopus up to July 10, 2023. Two authors independently appraised risk models using CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies (CHARMS) and assessed their risk of bias and applicability using Prediction model Risk Of Bias ASsessment Tool (PROBAST). RESULTS: Sixteen studies were included, describing 37 models. When studies presented multiple algorithms, we focused on the model that was selected as the best by the study authors. Eventually we appraised 19 models, among which 15 were regression models and four machine learning models. All models were at a high risk of bias, primarily due to inappropriate proxy outcomes, predictors that are unavailable at prediction time in clinical practice, inadequate sample size, negligence of missing data, lack of model validation, and absence of calibration assessment. 18 out of 19 models had a high concern for applicability, one model had unclear concern for applicability due to incomplete reporting. CONCLUSION: We did not identify a prediction model of potential clinical use. There is a pressing need to develop an applicable model for CLA-BSI.

Wearable technology and the cardiovascular system: the future of patient assessment.

The past decade has seen a dramatic rise in consumer technologies able to monitor a variety of cardiovascular parameters. Such devices initially recorded markers of exercise, but now include physiological and health-care focused measurements. The public are keen to adopt these devices in the belief that they are useful to identify and monitor cardiovascular disease. Clinicians are therefore often presented with health app data accompanied by a diverse range of concerns and queries. Herein, we assess whether these devices are accurate, their outputs validated, and whether they are suitable for professionals to make management decisions. We review underpinning methods and technologies and explore the evidence supporting the use of these devices as diagnostic and monitoring tools in hypertension, arrhythmia, heart failure, coronary artery disease, pulmonary hypertension, and valvular heart disease. Used correctly, they might improve health care and support research.

Artificial intelligence in medical device software and high-risk medical devices - a review of definitions, expert recommendations and regulatory initiatives.

INTRODUCTION: Artificial intelligence (AI) encompasses a wide range of algorithms with risks when used to support decisions about diagnosis or treatment, so professional and regulatory bodies are recommending how they should be managed. AREAS COVERED: AI systems may qualify as standalone medical device software (MDSW) or be embedded within a medical device. Within the European Union (EU) AI software must undergo a conformity assessment procedure to be approved as a medical device. The draft EU Regulation on AI proposes rules that will apply across industry sectors, while for devices the Medical Device Regulation also applies. In the CORE-MD project (Coordinating Research and Evidence for Medical Devices), we have surveyed definitions and summarize initiatives made by professional consensus groups, regulators, and standardization bodies. EXPERT OPINION: The level of clinical evidence required should be determined according to each application and to legal and methodological factors that contribute to risk, including accountability, transparency, and interpretability. EU guidance for MDSW based on international recommendations does not yet describe the clinical evidence needed for medical AI software. Regulators, notified bodies, manufacturers, clinicians and patients would all benefit from common standards for the clinical evaluation of high-risk AI applications and transparency of their evidence and performance.

The Left Ventricular Pressure-Volume Area and Stroke Work in Porcine Model of Ascending Compared to Descending Thoracic Aorta Stenosis Creating a Chronic Early Vs. Late Left Ventricular Afterload Increase.

Objective: Left ventricular hypertrophy in aortic stenosis, arterial hypertension or coarctation of the aorta is risk factor for early development of HF. In chronic late compared to early left ventricular afterload increases resulting from descending thoracic оr ascending aorta stenosis, we assess the left ventricular stroke work, pressure-volume area for О2 demand and effective work on the 4th and 8th weeks. It is suggested that reduced proximal thoracic aortic compliance presents with myocardial ischemia. However, development of adverse left ventricular hypertrophic remodeling and HF in different peak of LV afterload increase is understood poorly. Methods: Fourteen domestic male pigs (28 ± 3 kg) underwent descending thoracic or ascending aortic stenosis through posterior lateral thoracotomy, with cMRI and an invasive left ventricular pressure-volume loops' аrea assessment (Millar 5Fr pig-tailed conductance catheter) on the 4th and 8th weeks. Left ventricular stroke work and pressure-volume area PVA, parameter for LV O2 demand, were assessed in hypertrophic left ventricular remodeling, resulting from different peaks in LV afterload (late vs. early LV afterload) increase and we thus defined early adverse LV hypertrophic remodeling in linear and nonlinear end-systolic pressure-volume regression analysis. For this we used special software. Data was compared with two-way repeated measures ANOVA. Results presented are means ± (SEM) or medians and significance is set at p < 0.05. Results: The left ventricular nonlinear PVA was not different, in LL compared to EL on the 8th week and when using the linear regression analysis. Stroke work was not different. The linear and nonlinear potential energy were not different between LL vs. the EL group. Nonlinear bLVO2 demand was not different, being higher in LL compared to EL in the 8th week. Indexed PVA parameters were not different or changed between the 4th and 8th weeks, when being normalized for body surface-area (m²) or 100 grams of LV mass. Conclusion: The left ventricular potential energy, PVA with effective work and LVO2 demands are not different in hypertrophic LV remodeling in LL vs. EL group at the 8th week. Difference is not present when end-systolic pressure-volume relation is assessed from indexed LV volumes for m² BSA or 100 grams of LV mass. EL is as important as LL in increased LV afterloads based on LV work and mechanical coupling in this hypertensive heart failure model having preserved EF.

Prolonged Asynchronous Left Ventricular Isovolumic Relaxation Constant in Ascending Compared to Descending Thoracic Aortic Stenosis for Chronic Early Left Ventricular Afterload and Late Left Ventricular Afterload Increase.

Background: In arterial hypertension, left ventricular relaxation is affected early on in relation to a chronic difference in peak left ventricular afterload with early development of HF. Objective: in ascending compares to descending thoracic aortic stenosis, resulting in chronic late and early LV afterload increase, to assess the left ventricular isovolumic relaxation pressure decay constant through regression analysis, a parameter of left ventricular relaxation on the 4th and 8th week period from invasive left ventricular pressure measurements. Methods: fourteen pigs underwent posterolateral thoracotomy for ascending aortic stenosis, resulting in chronic early left ventricular afterload increase (EL = 6], or descending thoracic aortic stenosis creating chronic late systolic left ventricular load (LL = 8]. Exponential regression with nonzero asymptote for τ assessment, with linear and nonlinear regression were performed on isovolumic relaxation pressure decay from the left ventricular invasive pressure measurements on 4th and 8th week. Two-way repeated measurement ANOVA, post-hoc Tukey test and linear regression were performed for statistical analysis. Results presented are mean ± SEM or median (quartiles], with significance is at p < 0.05. Results: The ascending aortic stenosis associated with prolonged biexponential asynchronous τ, compared to the descending thoracic aorta stenosis, resulted in data that were different at the 8th week in presence of respirations (interaction p < 0.05]. Monoexponential and linear τ were not different in either respiration being preserved or suspended transitionally and in preload reduction. Preload sensitive response of τ was found in ascending compared to descending thoracic aortic banding that reduced in EL and in LL it increased with load reduction (p < 0.05]. These results indicated that τ is not different in and between LV afterloading conditions in a chronic setting, although it indicates that myocardial ischemia is present and that it is greater in ascending aortic banding, compared to descending thoracic aorta banding at the 8th week. Conclusion: In different sequence of the left ventricular afterload, ventricular relaxation is affected early on, having in EL compared to LL prolonged biexponential asynchronous left ventricular relaxation constant, thus indicating the development left ventricular myocardial ischemia and different elastic recoil in an invasive left ventricular hemodynamic assessment.

On the use of partitioning for scheduling of surgeries in the inpatient surgical department.

In hospitals, the efficient planning of the operating rooms (ORs) is difficult due to the uncertainty inherent to surgical services. This is especially true for the inpatient surgical department where complex and long surgeries are often performed along with surgeries on emergency patients. This paper aims to improve the scheduling of the inpatient department by partitioning the elective surgeries into the more predictable surgeries (MPS) group and the less predictable surgeries (LPS) group, based on surgery duration variability, and by scheduling each of the two surgery groups in different ORs. Through a simulation study that comprehensively investigates the impact of the partitioning on different performance measures under various environmental settings, we report important findings and insights. First, partitioning can effectively shorten the waiting times of elective patients for both MPS and LPS groups, but the option should be allowed to reassign patients from the MPS or LPS ORs to the other ORs when needed. Meanwhile, partitioning sometimes slightly increases the elective cancellation rate. Second, the ability to use the available capacity of the ORs as much as possible is key to reducing elective waiting times. Third, partitioning might slightly worsen the waiting times of emergency patients, while the slightly negative impact on emergency patients decreases when the number of ORs is higher. Fourth, the beneficial impact of partitioning on elective patients increases with an increased patient demand. Last, for the settings considered in this study there was no benefit in partitioning the elective patients into more than two groups.

Cardiac troponin T and NT-proBNP for detecting myocardial ischemia in suspected chronic coronary syndrome.

BACKGROUND: Elevated N-terminal pro-B-type natriuretic peptides (NT-proBNP) and cardiac troponin T (cTnT) are associated with poor outcome in patients with chronic coronary syndrome (CCS). The performance of these biomarkers in diagnosing ischemia, and their association with myocardial hypoperfusion and hypokinesis is unclear. METHODS: Patients with suspected CCS (history of angina, estimated cardiovascular risk >15% or a positive stress test) were included in the prospective, multi-center DOPPLER-CIP study. Patients underwent Single Positron Emission Computed Tomography for assessment of ischemia and NT-proBNP and cTnT were measured in venous blood samples. RESULTS: We included 430 patients (25% female) aged 64 ± 8 years. Reversible hypoperfusion and hypokinesis were present in 139 (32%) and 89 (21%), respectively. Concentrations of NT-proBNP and cTnT correlated moderately (rho = 0.50, p < 0.001). NT-proBNP and cTnT concentrations (median [IQR]) were higher in patients with versus without reversible ischemia: 150 (73-294) versus 87 (44-192) ng/L and 10 (6-13) versus 7 (4-11) ng/L, respectively (p < 0.001 for both), and the associations persisted after adjusting for possible confounders. The C-statistics to discriminate ischemia ranged from 63%-73%, were comparable for cTnT and NT-proBNP, and higher for hypokinesis than hypoperfusion, and both were superior to exercise electrocardiography and stress echocardiography. Very low concentrations (≤5 ng/L cTnT and ≤ 60 ng/L NT-proBNP) ruled out reversible hypokinesis with negative predictive value >90%. CONCLUSION: cTnT and NT-proBNP are associated with irreversible and reversible ischemia in patients with suspected CCS, particularly hypokinesis. The diagnostic performance was comparable between the biomarkers, and very low concentrations may reliably rule out ischemia.

Cost-Minimization Analysis for Cardiac Revascularization in 12 Health Care Systems Based on the EuroCMR/SPINS Registries.

OBJECTIVES: The aim of this study was to compare the costs of a noninvasive cardiac magnetic resonance (CMR)-guided strategy versus 2 invasive strategies with and without fractional flow reserve (FFR). BACKGROUND: Coronary artery disease (CAD) is a major contributor to the public health burden. Stress perfusion CMR has excellent accuracy to detect CAD. International guidelines recommend as a first step noninvasive testing of patients in stable condition with known or suspected CAD. However, nonadherence in routine clinical practice is high. METHODS: In the EuroCMR (European Cardiovascular Magnetic Resonance) registry (n = 3,647, 59 centers, 18 countries) and the U.S.-based SPINS (Stress-CMR Perfusion Imaging in the United States) registry (n = 2,349, 13 centers, 11 states), costs were calculated for 12 health care systems (8 in Europe, the United States, 2 in Latin America, and 1 in Asia). Costs included diagnostic examinations (CMR and x-ray coronary angiography [CXA] with and without FFR), revascularizations, and complications during 1-year follow-up. Seven subgroup analyses covered low- to high-risk cohorts. Patients with ischemia-positive CMR underwent CXA and revascularization at the treating physician's discretion (CMR+CXA strategy). In the hypothetical invasive CXA+FFR strategy, costs were calculated for initial CXA and FFR in vessels with ≥50% stenoses, assuming the same proportion of revascularizations and complications as with the CMR+CXA strategy and FFR-positive rates as given in the published research. In the CXA-only strategy, costs included CXA and revascularizations of ≥50% stenoses. RESULTS: Consistent cost savings were observed for the CMR+CXA strategy compared with the CXA+FFR strategy in all 12 health care systems, ranging from 42% ± 20% and 52% ± 15% in low-risk EuroCMR and SPINS patients with atypical chest pain, respectively, to 31% ± 16% in high-risk SPINS patients with known CAD (P < 0.0001 vs 0 in all groups). Cost savings were even higher compared with CXA only, at 63% ± 11%, 73% ± 6%, and 52% ± 9%, respectively (P < 0.0001 vs 0 in all groups). CONCLUSIONS: In 12 health care systems, a CMR+CXA strategy yielded consistent moderate to high cost savings compared with a hypothetical CXA+FFR strategy over the entire spectrum of risk. Cost savings were consistently high compared with CXA only for all risk groups.

Experimental validation of the prestretch-strain relationship as a non-invasive index of left ventricular myocardial contractility.

BACKGROUND: The slope of the relationship between segmental PreS and total systolic shortening (S) has been proposed as a non-invasive index of left ventricular contractility. The aim of this study was to correlate this novel parameter to invasive gold standard measurements of contractility and to investigate how it is influenced by afterload. METHODS: In domestic pigs, afterload was increased by either balloon inflation in the aorta or by administration of phenylephrine while contractility was increased by dobutamine infusion. During all interventions, left ventricular pressure-volume measurements and trans-diaphragmatic two-dimensional echocardiographic images were acquired. The PreS-S slope was constructed from 18 segmental strain curves obtained by speckle tracking analysis and compared to the slope of the end systolic PV relationship (Emax) and the pre-load recruitable stroke work (PRSW). RESULTS: Sixteen datasets of increased contractility and afterload were analyzed. During dobutamine infusion, the LV volumes decreased (p<0.05) while ejection fraction increased (p<0.05). Emax, PRSW and the slope of the intra-ventricular PreS-S relation increased significantly during dobutamine infusion. Afterload increase led to increase in systolic blood pressure (105±16mmHg vs. 138±25mmHg; p<0.01) and decrease of LV stroke volume and ejection fraction (p<0.01). The PreS-S slope was not influenced by loading conditions in concordance with the PRSW findings. The absolute values of the PreS-S slope did not correlate with Emax or PRSW. However, the change of the PreS-S slope in relation with different interventions demonstrated good correlation with changes in PRSW or Emax, (r = 0.66, p<0.05 and r = 0.69, p<0.05). CONCLUSIONS: The slope of the PreS-S relationship is sensitive to changes in inotropy and is less load-dependent than conventional non-invasive parameters of left ventricular function. The magnitude of the change of this slope correlates well with changes in invasive contractility measurements making it an attractive parameter to assess contractile reserve or contractile changes during longitudinal follow-up of patients.

Translating Data From an Electronic Prescribing and Medicines Administration System Into Knowledge: Application to Doctor-Nurse Time Discrepancy in Antibiotic Ordering and Administration.

BACKGROUND: Electronic Prescribing and Medicines Administration (EPMA) systems are being widely implemented to facilitate medication safety improvement. However, translating the resulting big data into actionable knowledge has received relatively little attention. OBJECTIVE: The objective of this study was to use routinely collected EPMA data in the study of exact time discrepancy between physicians' order and nurses' administration of systemic antibiotics. We evaluated first and follow-up dose administration and dose intervals and examined multifactorial determinants in ordering and administration explaining potential discrepancy. METHODS: We conducted an observational study of electronic health records for all medical patient stays with antibiotic treatment from January to June 2018 (n=4392) in a large Belgian tertiary care hospital. Using an EPMA system with Barcode Medication Administration, we calculated time discrepancy between order and administration of first doses (n=6233), follow-up doses (n=87 960), and dose intervals. Multiple logistic regression analysis estimated the association between time discrepancy and various determinants in ordering and administration. RESULTS: Time discrepancy between physician order and nurse administration was <30 minutes for 48.7% of first doses and 61.7% of follow-up doses, with large variation across primary diagnoses. Greater dose intervals, oral versus intravenous administration, and order diversion from regular nurse administration rounds showed strongest association with less timely administration. CONCLUSIONS: EPMA systems show huge potential to generate actionable knowledge. Concerning antibiotic treatment, having physicians' orders coincide with regular nurse administration rounds whenever clinically appropriate, further taking contextual factors into account, could potentially improve antibiotic administration timeliness.

Standardised mortality ratios as a user-friendly performance metric and trigger for quality improvement in a Flemish hospital network: multicentre retrospective study.

OBJECTIVE: To illustrate the development and use of standardised mortality rates (SMRs) as a trigger for quality improvement in a network of 27 hospitals. DESIGN: This research was a retrospective observational study. The primary outcome was in-hospital mortality. SMRs were calculated for All Patient Refined-Diagnosis-Related Groups (APR-DRGs) that reflect 80% of the Flemish hospital network mortality. Hospital mortality was modelled using logistic regression. The metrics were communicated to the member hospitals using a custom-made R-Shiny web application showing results at the level of the hospital, patient groups and individual patients. Experiences with the metric and strategies for improvement were shared in chief medical officer meetings organised by the Flemish hospital network. SETTING: 27 Belgian hospitals. PARTICIPANTS: 1 198 717 hospital admissions for registration years 2009-2016. RESULTS: Patient gender, age, comorbidity as well as admission source and type were important predictors of mortality. Altogether the SMR models had a C-statistic of 88%, indicating good discriminatory capability. Seven out of ten APR-DRGs with the highest percentage of hospitals statistically significantly deviating from the benchmark involved malignancy. The custom-built web application and the trusted environment of the Flemish hospital network created an interoperable strategy to get to work with SMR findings. Use of the web application increased over time, with peaks before and after key discussion meetings within the Flemish hospital network. A concomitant reduction in crude mortality for the selected APR-DRGs from 6.7% in 2009 to 5.9% in 2016 was observed. CONCLUSIONS: This study reported on the phased approach for introducing SMR reporting to trigger quality improvement. Prerequisites for the successful use of quality metrics in hospital benchmarks are a collaborative approach based on trust among the participants and a reporting platform that allows stakeholders to interpret and analyse the results at multiple levels.

Cardiac Troponin T Concentrations, Reversible Myocardial Ischemia, and Indices of Left Ventricular Remodeling in Patients with Suspected Stable Angina Pectoris: a DOPPLER-CIP Substudy.

BACKGROUND: Cardiac troponin T concentrations measured with high-sensitivity assays (hs-cTnT) provide important prognostic information for patients with stable coronary artery disease (CAD). However, whether hs-cTnT concentrations mainly reflect left ventricular (LV) remodeling or recurrent myocardial ischemia in this population is not known. METHODS: We measured hs-cTnT concentrations in 619 subjects with suspected stable CAD in a prospectively designed multicenter study. We identified associations with indices of LV remodeling, as assessed by cardiac MRI and echocardiography, and evidence of myocardial ischemia diagnosed by single positron emission computed tomography. RESULTS: Median hs-cTnT concentration was 7.8 ng/L (interquartile range, 4.8-11.6 ng/L), and 111 patients (18%) had hs-cTnT concentrations above the upper reference limit (>14 ng/L). Patients with hs-cTnT >14 ng/L had increased LV mass (144 ± 40 g vs 116 ± 34 g; P < 0.001) and volume (179 ± 80 mL vs 158 ± 44 mL; P = 0.006), lower LV ejection fraction (LVEF) (59 ± 14 vs 62 ± 11; P = 0.006) and global longitudinal strain (14.1 ± 3.4% vs 16.9 ± 3.2%; P < 0.001), and more reversible perfusion defects (P = 0.001) and reversible wall motion abnormalities (P = 0.008). Age (P = 0.009), estimated glomerular filtration rate (P = 0.01), LV mass (P = 0.003), LVEF (P = 0.03), and evidence of reversible myocardial ischemia (P = 0.004 for perfusion defects and P = 0.02 for LV wall motion) were all associated with increasing hs-cTnT concentrations in multivariate analysis. We found analogous results when using the revised US upper reference limit of 19 ng/L. CONCLUSIONS: hs-cTnT concentrations reflect both LV mass and reversible myocardial ischemia in patients with suspected stable CAD.

Serial assessment of left ventricular morphology and function in a rodent model of ischemic cardiomyopathy.

Left ventricular remodelling (LVr) occurs post myocardial infarction (MI), predisposing people to heart failure (HF). LV mechanics and morphology are important in this process. We hence sort to characterize LV mechanics and geometry in a post-MI rodent model. Thirty-two male Sprague-Dawley rats (150-200 g) sustained MI (n = 24) or sham (Sham; n = 8) surgery. In another six sham rats invasive blood pressure measurements were performed. Ultrasound imaging was done at baseline, and 1, 3, 7, 14, 30 and 60 days following surgery, and LV mechanics and morphology assessed. LV volumes increased with time (p < 0.01), at a greater rate in the MI group than the Sham group (p < 0.01). Strain was impaired in MI rats at day 1 (13.50 ± 6.64 vs. 25.71 ± 4.94%, p < 0.01) and remained impaired at day 60 (14.07 ± 5.37 vs. 22.98 ± 5.87%, p < 0.01). Strain rate was lower at day 1 (4.11 ± 1.29 vs. 8.10 ± 2.18%/s, p < 0.01), remained lower throughout follow-up (p < 0.01), and decreased at a greater rate in MI rats (p < 0.01). Mean systolic (204 ± 43 vs. 322 ± 75 1/m, p < 0.01) and diastolic (167 ± 21 vs. 192 ± 11 1/m, p < 0.01) curvature was lower in the MI rats at day 1 post surgery and throughout follow-up (p < 0.01). Maximum principal curvature decreased throughout time (p < 0.01), while minimum principal curvature did not (p = 0.86). Wall stress increased significantly after infarction in MI rats (p < 0.01). ST-elevation myocardial infarction (STEMI) changed LV shape and contractile function. The assessment of these indices may prove useful in understanding LVr and the development of HF.

Exercise physiology with a left ventricular assist device: Analysis of heart-pump interaction with a computational simulator.

Patients with a Ventricular Assist Device (VAD) are hemodynamically stable but show an impaired exercise capacity. Aim of this work is to identify and to describe the limiting factors of exercise physiology with a VAD. We searched for data concerning exercise in heart failure condition and after VAD implantation from the literature. Data were analyzed by using a cardiorespiratory simulator that worked as a collector of inputs coming from different papers. As a preliminary step the simulator was used to reproduce the evolution of hemodynamics from rest to peak exercise (ergometer cycling) in heart failure condition. Results evidence an increase of cardiac output of +2.8 l/min and a heart rate increase to 67% of the expected value. Then, we simulated the effect of a continuous-flow VAD at both rest and exercise. Total cardiac output increases of +3.0 l/min (+0.9 l/min due to the VAD and +2.1 l/min to the native ventricle). Since the left ventricle works in a non-linear portion of the diastolic stiffness line, we observed a consistent increase of pulmonary capillary wedge pressure (from 14 to 20 mmHg) for a relatively small increase of end-diastolic volume (from 182 to 189 cm3). We finally increased VAD speed during exercise to the maximum possible value and we observed a reduction of wedge pressure (-4.5 mmHg), a slight improvement of cardiac output (8.0 l/min) and a complete unloading of the native ventricle. The VAD can assure a proper hemodynamics at rest, but provides an insufficient unloading of the left ventricle and does not prevent wedge pressure from rising during exercise. Neither the VAD provides major benefits during exercise in terms of total cardiac output, which increases to a similar extend to an unassisted heart failure condition. VAD speed modulation can contribute to better unload the ventricle but the maximal flow reachable with the current devices is below the cardiac output observed in a healthy heart.