Table 0; documenting the steps to go from clinical database to research dataset.

OBJECTIVES: Data-driven decision support tools have been increasingly recognized to transform health care. However, such tools are often developed on predefined research datasets without adequate knowledge of the origin of this data and how it was selected. How a dataset is extracted from a clinical database can profoundly impact the validity, interpretability and interoperability of the dataset, and downstream analyses, yet is rarely reported. Therefore, we present a case study illustrating how a definitive patient list was extracted from a clinical source database and how this can be reported. STUDY DESIGN AND SETTING: A single-center observational study was performed at an academic hospital in the Netherlands to illustrate the impact of selecting a definitive patient list for research from a clinical source database, and the importance of documenting this process. All admissions from the critical care database admitted between January 1, 2013, and January 1, 2023, were used. RESULTS: An interdisciplinary team collaborated to identify and address potential sources of data insufficiency and uncertainty. We demonstrate a stepwise data preparation process, reducing the clinical source database of 54,218 admissions to a definitive patient list of 21,553 admissions. Transparent documentation of the data preparation process improves the quality of the definitive patient list before analysis of the corresponding patient data. This study generated seven important recommendations for preparing observational health-care data for research purposes. CONCLUSION: Documenting data preparation is essential for understanding a research dataset originating from a clinical source database before analyzing health-care data. The findings contribute to establishing data standards and offer insights into the complexities of preparing health-care data for scientific investigation. Meticulous data preparation and documentation thereof will improve research validity and advance critical care.

The laboratory parameters-derived CoLab score as an indicator of the host response in ICU COVID-19 patients decreases over time: a prospective cohort study.

The CoLab score was developed and externally validated to rule out COVID-19 among suspected patients presenting at the emergency department. We hypothesized a within-patient decrease in the CoLab score over time in an intensive care unit (ICU) cohort. Such a decrease would create the opportunity to potentially rule out the need for isolation when the infection is overcome. Using linear mixed-effects models, data from the Maastricht Intensive Care COVID (MaastrICCht) cohort were used to investigate the association between time and the CoLab score. Models were adjusted for sex, APACHE II score, ICU mortality, and daily SOFA score. The CoLab score decreased by 0.30 points per day (95% CI - 0.33 to - 0.27), independent of sex, APACHE II, and Mortality. With increasing SOFA score over time, the CoLab score decreased more strongly (- 0.01 (95% CI - 0.01 to - 0.01) additional decrease per one-point increase in SOFA score.) The CoLab score decreased in ICU patients on mechanical ventilation for COVID-19, with a one-point reduction per three days, independent of sex, APACHE II, and ICU mortality, and somewhat stronger with increasing multi-organ failure over time. This suggests that the CoLab score would decrease below a threshold where COVID-19 can be excluded.

The association between coronary artery calcification and vectorcardiography in mechanically ventilated COVID-19 patients: the Maastricht Intensive Care COVID cohort.

BACKGROUND: Coronary artery calcification (CAC) is associated with poor outcome in critically ill patients. A deterioration in cardiac conduction and loss of myocardial tissue could be an underlying cause. Vectorcardiography (VCG) and cardiac biomarkers provide insight into these underlying causes. The aim of this study was to investigate whether a high degree of CAC is associated with VCG-derived variables and biomarkers, including high-sensitivity troponin-T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). METHODS: Mechanically ventilated coronavirus-19 (COVID-19) patients with an available chest computed tomography (CT) and 12-lead electrocardiogram (ECG) were studied. CAC scores were determined using chest CT scans. Patients were categorized into 3 sex-specific tertiles: low, intermediate, and high CAC. Daily 12 leads-ECGs were converted to VCGs. Daily hs-cTnT and NT-proBNP levels were determined. Linear mixed-effects regression models examined the associations between CAC tertiles and VCG variables, and between CAC tertiles and hs-cTnT or NT-proBNP levels. RESULTS: In this study, 205 patients (73.2% men, median age 65 years [IQR 57.0; 71.0]) were included. Compared to the lowest CAC tertile, the highest CAC tertile had a larger QRS area at baseline (6.65 µVs larger [1.50; 11.81], p = 0.012), which decreased during admission (- 0.27 µVs per day [- 0.43; - 0.11], p = 0.001). Patients with the highest CAC tertile also had a longer QRS duration (12.02 ms longer [4.74; 19.30], p = 0.001), higher levels of log hs-cTnT (0.79 ng/L higher [0.40; 1.19], p < 0.001) and log NT-proBNP (0.83 pmol/L higher [0.30; 1.37], p = 0.002). CONCLUSION: Patients with a high degree of CAC had the largest QRS area and higher QRS amplitude, which decreased more over time when compared to patients with a low degree of CAC. These results suggest that CAC might contribute to loss of myocardial tissue during critical illness. These insights could improve risk stratification and prognostication of patients with critical illness.

The CoLab score is associated with SARS-CoV-2 viral load during admission in individuals admitted to the intensive care unit: the CoLaIC cohort study.

OBJECTIVES: The present study examines the temporal association between the changes in SARS-CoV-2 viral load during infection and whether the CoLab-score can facilitate de-isolation. METHODS: Nasal swabs and blood samples were collected from ICU-admitted SARS-CoV-2 positive patients at Maastricht UMC+ from March 25, 2020 to October 1, 2021. The CoLab-score was calculated based on 10 blood parameters and age and can range from -43 to 6. Three mixed effects analyses compared patient categories based on initial PCR Ct values (low; Ct≤20, mid; 20>Ct≤30, high; Ct>30), serial PCR Ct values to CoLab-scores over time, and the association between within-patient delta Ct values and CoLab-scores. RESULTS: In 324 patients, the median Ct was 33, and the median CoLab-score was -1.78. Mid (n=110) and low (n=41) Ct-categories had higher CoLab-scores over time (+0.60 points, 95 % CI; 0.04-1.17, and +0.28 points, 95 % CI -0.49 to 1.04) compared to the high Ct (n=87) category. Over time, higher serial Ct values were associated with lower serial CoLab-scores, decreasing by -0.07 points (95 % CI; -0.11 to -0.02) per day. Increasing delta Ct values were associated with a decreasing delta CoLab-score of -0.12 (95 % CI; -0.23; -0.01). CONCLUSIONS: The study found an association between lower viral load on admission and reduced CoLab-score. Additionally, a decrease in viral load over time was associated with a decrease in CoLab-score. Therefore, the CoLab-score may make patient de-isolation an option based on the CoLab-score.

Deep embedded clustering generalisability and adaptation for integrating mixed datatypes: two critical care cohorts.

We validated a Deep Embedded Clustering (DEC) model and its adaptation for integrating mixed datatypes (in this study, numerical and categorical variables). Deep Embedded Clustering (DEC) is a promising technique capable of managing extensive sets of variables and non-linear relationships. Nevertheless, DEC cannot adequately handle mixed datatypes. Therefore, we adapted DEC by replacing the autoencoder with an X-shaped variational autoencoder (XVAE) and optimising hyperparameters for cluster stability. We call this model "X-DEC". We compared DEC and X-DEC by reproducing a previous study that used DEC to identify clusters in a population of intensive care patients. We assessed internal validity based on cluster stability on the development dataset. Since generalisability of clustering models has insufficiently been validated on external populations, we assessed external validity by investigating cluster generalisability onto an external validation dataset. We concluded that both DEC and X-DEC resulted in clinically recognisable and generalisable clusters, but X-DEC produced much more stable clusters.

Rotational thromboelastometry as a biomarker for mortality - The Maastricht Intensive Care COVID cohort.

BACKGROUND: Patients with severe coronavirus disease 2019 (COVID-19) present with persisting hypercoagulability, hypofibrinolysis and prolonged clot initiation as measured with viscoelastic assays. The objective of this study was to investigate the trajectories of traditional assays of hemostasis, routine and tissue plasminogen activator (tPA) rotational thromboelastometry (ROTEM) in COVID-19 patients and to study their association with mortality. METHODS: Patients enrolled within the Maastricht Intensive Care COVID (MaastrICCht) cohort were included. Traditional assays of hemostasis (prothrombin time; PT, fibrinogen and D-dimer) were measured daily and ROTEM EXTEM, FIBTEM and tPA assays were performed weekly. Trajectories of these biomarkers were analyzed over time for survivors and non-survivors using linear mixed-effects models. Additional Fine and Gray competing risk survival analysis was performed for the first available measurement after intubation. RESULTS: Of the 138 included patients, 57 (41 %) died in the intensive care unit (ICU). Over 450, 400 and 1900 individual measurements were available for analysis of routine, tPA ROTEM and traditional assays of hemostasis, respectively, with a median [IQR] follow-up of 15 [8-24] days. Non-survivors on average had prolonged CT (clotting time) and increased fibrinogen compared to survivors. MCF (maximum clot firmness), LOT (lysis onset time), LT (lysis time) and PT measurements increased more over time in non-survivors compared to survivors. Associations persisted after adjustment for demographics and disease severity. EXTEM and FIBTEM CT at intubation were associated with increased 45-day ICU mortality. CONCLUSIONS: ROTEM measurements demonstrate a further increase of hypercoagulability and (hypo)fibrinolysis parameters in non-survivors throughout ICU admission. Furthermore, prolonged CT at intubation was associated with higher 45-day ICU mortality.

Serial electrical impedance tomography course in different treatment groups; The MaastrICCht cohort.

PURPOSE: To describe the effect of dexamethasone and tocilizumab on regional lung mechanics over admission in all mechanically ventilated COVID-19 patients. MATERIALS AND METHODS: Dynamic compliance, alveolar overdistension and collapse were serially determined using electric impedance tomography (EIT). Patients were categorized into three groups; no anti-inflammatory therapy, dexamethasone therapy, dexamethasone + tocilizumab therapy. The EIT variables were (I) visualized using polynomial regression, (II) evaluated throughout admission using linear mixed-effects models, and (III) average respiratory variables were compared. RESULTS: Visual inspection of EIT variables showed a pattern of decreasing dynamic compliance. Overall, optimal set PEEP was lower in the dexamethasone group (-1.4 cmH2O, -2.6; -0.2). Clinically applied PEEP was lower in the dexamethasone and dexamethasone + tocilizumab group (-1.5 cmH2O, -2.6; -0.2; -2.2 cmH2O, -5.1; 0.6). Dynamic compliance, alveolar overdistension, and alveolar collapse at optimal set PEEP did not significantly differ between the three groups. CONCLUSION: Optimal and clinically applied PEEP were lower in the dexamethasone and dexamethasone + tocilizumab groups. The results suggest that the potential beneficial effects of these therapies do not affect lung mechanics favorably. However, this study cannot fully rule out any beneficial effect of anti-inflammatory treatment on pulmonary function due to its observational nature.

Hyperglycemia and glucose variability are associated with worse survival in mechanically ventilated COVID-19 patients: the prospective Maastricht Intensive Care Covid Cohort.

BACKGROUND: Data on hyperglycemia and glucose variability in relation to diabetes mellitus, either known or unknown in ICU-setting in COVID-19, are scarce. We prospectively studied daily glucose variables and mortality in strata of diabetes mellitus and glycosylated hemoglobin among mechanically ventilated COVID-19 patients. METHODS: We used linear-mixed effect models in mechanically ventilated COVID-19 patients to investigate mean and maximum difference in glucose concentration per day over time. We compared ICU survivors and non-survivors and tested for effect-modification by pandemic wave 1 and 2, diabetes mellitus, and admission HbA1c. RESULTS: Among 232 mechanically ventilated COVID-19 patients, 21.1% had known diabetes mellitus, whereas 16.9% in wave 2 had unknown diabetes mellitus. Non-survivors had higher mean glucose concentrations (ß 0.62 mmol/l; 95%CI 0.20-1.06; ß 11.2 mg/dl; 95% CI 3.6-19.1; P = 0.004) and higher maximum differences in glucose concentrations per day (ß 0.85 mmol/l; 95%CI 0.37-1.33; ß 15.3; 95%CI 6.7-23.9; P = 0.001). Effect modification by wave, history of diabetes mellitus and admission HbA1c in associations between glucose and survival was not present. Effect of higher mean glucose concentrations was modified by pandemic wave (wave 1 (ß 0.74; 95% CI 0.24-1.23 mmol/l) ; (ß 13.3; 95%CI 4.3-22.1 mg/dl)) vs. (wave 2 (ß 0.37 (95%CI 0.25-0.98) mmol/l) (ß 6.7 (95% ci 4.5-17.6) mg/dl)). CONCLUSIONS: Hyperglycemia and glucose variability are associated with mortality in mechanically ventilated COVID-19 patients irrespective of the presence of diabetes mellitus.

Higher levels of circulating desphospho-uncarboxylated matrix Gla protein over time are associated with worse survival: the prospective Maastricht Intensive Care COVID cohort.

BACKGROUND: Extra-hepatic vitamin K-status, measured by dephosphorylated uncarboxylated matrix Gla protein (dp-ucMGP), maintains vascular health, with high levels reflecting poor vitamin K status. The occurrence of extra-hepatic vitamin K deficiency throughout the disease of COVID-19 and possible associations with pulmonary embolism (PE), and mortality in intensive care unit (ICU) patients has not been studied. The aim of this study was to investigated the association between dp-ucMGP, at endotracheal intubation (ETI) and both ICU and six months mortality. Furthermore, we studied the associations between serially measured dp-ucMGP and both PE and mortality. METHODS: We included 112 ICU patients with confirmed COVID-19. Over the course of 4 weeks after ETI, dp-ucMGP was measured serially. All patients underwent computed tomography pulmonary angiography (CTPA) to rule out PE. Results were adjusted for patient characteristics, disease severity scores, inflammation, renal function, history of coumarin use, and coronary artery calcification (CAC) scores. RESULTS: Per 100 pmol/L dp-ucMGP, at ETI, the odds ratio (OR) was 1.056 (95% CI: 0.977 to 1.141, p = 0.172) for ICU mortality and 1.059 (95% CI: 0.976 to 1.059, p = 0.170) for six months mortality. After adjustments for age, gender, and APACHE II score, the mean difference in plasma dp-ucMGP over time of ICU admission was 167 pmol/L (95% CI: 4 to 332, p = 0.047). After additional adjustments for c-reactive protein, creatinine, and history of coumarin use, the difference was 199 pmol/L (95% CI: 50 to 346, p = 0.010). After additional adjustment for CAC score the difference was 213 pmol/L (95% CI: 3 to 422, p = 0.051) higher in ICU non-survivors compared to the ICU survivors. The regression slope, indicating changes over time, did not differ. Moreover, dp-ucMGP was not associated with PE. CONCLUSION: ICU mortality in COVID-19 patients was associated with higher dp-ucMGP levels over 4 weeks, independent of age, gender, and APACHE II score, and not explained by inflammation, renal function, history of coumarin use, and CAC score. No association with PE was observed. At ETI, higher levels of dp-ucMGP were associated with higher OR for both ICU and six month mortality in crude and adjusted modes, although not statistically significantly.

Regional variability in intracerebral properties of NREM to REM sleep transitions in humans.

Transitions between wake and sleep states show a progressive pattern underpinned by local sleep regulation. In contrast, little evidence is available on non-rapid eye movement (NREM) to rapid eye movement (REM) sleep boundaries, considered as mainly reflecting subcortical regulation. Using polysomnography (PSG) combined with stereoelectroencephalography (SEEG) in humans undergoing epilepsy presurgical evaluation, we explored the dynamics of NREM-to-REM transitions. PSG was used to visually score transitions and identify REM sleep features. SEEG-based local transitions were determined automatically with a machine learning algorithm using features validated for automatic intra-cranial sleep scoring (10.5281/zenodo.7410501). We analyzed 2988 channel-transitions from 29 patients. The average transition time from all intracerebral channels to the first visually marked REM sleep epoch was 8 s ± 1 min 58 s, with a great heterogeneity between brain areas. Transitions were observed first in the lateral occipital cortex, preceding scalp transition by 1 min 57 s ± 2 min 14 s (d = -0.83), and close to the first sawtooth wave marker. Regions with late transitions were the inferior frontal and orbital gyri (1 min 1 s ± 2 min 1 s, d = 0.43, and 1 min 1 s ± 2 min 5 s, d = 0.43, after scalp transition). Intracranial transitions were earlier than scalp transitions as the night advanced (last sleep cycle, d = -0.81). We show a reproducible gradual pattern of REM sleep initiation, suggesting the involvement of cortical mechanisms of regulation. This provides clues for understanding oneiric experiences occurring at the NREM/REM boundary.

Validating a clinical laboratory parameter-based deisolation algorithm for patients with COVID-19 in the intensive care unit using viability PCR: the CoLaIC multicentre cohort study protocol.

INTRODUCTION: To investigate whether biochemical and haematological changes due to the patient's host response (CoLab algorithm) in combination with a SARS-CoV-2 viability PCR (v-PCR) can be used to determine when a patient with COVID-19 is no longer infectious.We hypothesise that the CoLab algorithm in combination with v-PCR can be used to determine whether or not a patient with COVID-19 is infectious to facilitate the safe release of patients with COVID-19 from isolation. METHODS AND ANALYSIS: This study consists of three parts using three different cohorts of patients. All three cohorts contain clinical, vital and laboratory parameters, as well as logistic data related to isolated patients with COVID-19, with a focus on intensive care unit (ICU) stay. The first cohort will be used to develop an algorithm for the course of the biochemical and haematological changes of the host response of the COVID-19 patient. Simultaneously, a second prospective cohort will be used to investigate the algorithm derived in the first cohort, with daily measured laboratory parameters, next to conventional SARS-CoV-2 reverse transcriptase PCRs, as well as v-PCR, to confirm the presence of intact SARS-CoV-2 particles in the patient. Finally, a third multicentre cohort, consisting of retrospectively collected data from patients with COVID-19 admitted to the ICU, will be used to validate the algorithm. ETHICS AND DISSEMINATION: This study was approved by the Medical Ethics Committee from Maastricht University Medical Centre+ (cohort I: 2020-1565/300523) and Zuyderland MC (cohorts II and III: METCZ20200057). All patients will be required to provide informed consent. Results from this study will be disseminated via peer-reviewed journals and congress/consortium presentations.

Pulmonary pathophysiology development of COVID-19 assessed by serial Electrical Impedance Tomography in the MaastrICCht cohort.

Patients with SARS-CoV-2 infection present with different lung compliance and progression of disease differs. Measures of lung mechanics in SARS-CoV-2 patients may unravel different pathophysiologic mechanisms during mechanical ventilation. The objective of this prospective observational study is to describe whether Electrical Impedance Tomography (EIT) guided positive end-expiratory pressure (PEEP) levels unravel changes in EIT-derived parameters over time and whether the changes differ between survivors and non-survivors. Serial EIT-measurements of alveolar overdistension, collapse, and compliance change in ventilated SARS-CoV-2 patients were analysed. In 80 out of 94 patients, we took 283 EIT measurements (93 from day 1-3 after intubation, 66 from day 4-6, and 124 from day 7 and beyond). Fifty-one patients (64%) survived the ICU. At admission mean PaO2/FiO2-ratio was 184.3 (SD 61.4) vs. 151.3 (SD 54.4) mmHg, (p = 0.017) and PEEP was 11.8 (SD 2.8) cmH2O vs. 11.3 (SD 3.4) cmH2O, (p = 0.475), for ICU survivors and non-survivors. At day 1-3, compliance was ~ 55 mL/cmH2O vs. ~ 45 mL/cmH2O in survivors vs. non-survivors. The intersection of overdistension and collapse curves appeared similar at a PEEP of ~ 12-13 cmH2O. At day 4-6 compliance changed to ~ 50 mL/cmH2O vs. ~ 38 mL/cmH2O. At day 7 and beyond, compliance was ~ 38 mL/cmH2O with the intersection at a PEEP of ~ 9 cmH2O vs. ~ 25 mL/cmH2O with overdistension intersecting at collapse curves at a PEEP of ~ 7 cmH2O. Surviving SARS-CoV-2 patients show more favourable EIT-derived parameters and a higher compliance compared to non-survivors over time. This knowledge is valuable for discovering the different groups.

Serial Assessment of Myocardial Injury Markers in Mechanically Ventilated Patients With SARS-CoV-2 (from the Prospective MaastrICCht Cohort).

Myocardial injury in COVID-19 is associated with in-hospital mortality. However, the development of myocardial injury over time and whether myocardial injury in patients with COVID-19 at the intensive care unit is associated with outcome is unclear. This study prospectively investigates myocardial injury with serial measurements over the full course of intensive care unit admission in mechanically ventilated patients with COVID-19. As part of the prospective Maastricht Intensive Care COVID cohort, predefined myocardial injury markers, including high-sensitivity cardiac troponin T (hs-cTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and electrocardiographic characteristics were serially collected in mechanically ventilated patients with COVID-19. Linear mixed-effects regression was used to compare survivors with nonsurvivors, adjusting for gender, age, APACHE-II score, daily creatinine concentration, hypertension, diabetes mellitus, and obesity. In 90 patients, 57 (63%) were survivors and 33 (37%) nonsurvivors, and a total of 628 serial electrocardiograms, 1,565 hs-cTnT, and 1,559 NT-proBNP concentrations were assessed. Log-hs-cTnT was lower in survivors compared with nonsurvivors at day 1 (ß -0.93 [-1.37; -0.49], p <0.001) and did not change over time. Log-NT-proBNP did not differ at day 1 between both groups but decreased over time in the survivor group (ß -0.08 [-0.11; -0.04] p <0.001) compared with nonsurvivors. Many electrocardiographic abnormalities were present in the whole population, without significant differences between both groups. In conclusion, baseline hs-cTnT and change in NT-proBNP were strongly associated with mortality. Two-thirds of patients with COVID-19 showed electrocardiographic abnormalities. Our serial assessment suggests that myocardial injury is common in mechanically ventilated patients with COVID-19 and is associated with outcome.

Vital Signs Prediction for COVID-19 Patients in ICU.

This study introduces machine learning predictive models to predict the future values of the monitored vital signs of COVID-19 ICU patients. The main vital sign predictors include heart rate, respiration rate, and oxygen saturation. We investigated the performances of the developed predictive models by considering different approaches. The first predictive model was developed by considering the following vital signs: heart rate, blood pressure (systolic, diastolic and mean arterial, pulse pressure), respiration rate, and oxygen saturation. Similar to the first approach, the second model was developed using the same vital signs, but it was trained and tested based on a leave-one-subject-out approach. The third predictive model was developed by considering three vital signs: heart rate (HR), respiration rate (RR), and oxygen saturation (SpO2). The fourth model was a leave-one-subject-out model for the three vital signs. Finally, the fifth predictive model was developed based on the same three vital signs, but with a five-minute observation rate, in contrast with the aforementioned four models, where the observation rate was hourly to bi-hourly. For the five models, the predicted measurements were those of the three upcoming observations (on average, three hours ahead). Based on the obtained results, we observed that by limiting the number of vital sign predictors (i.e., three vital signs), the prediction performance was still acceptable, with the average mean absolute percentage error (MAPE) being 12%,5%, and 21.4% for heart rate, oxygen saturation, and respiration rate, respectively. Moreover, increasing the observation rate could enhance the prediction performance to be, on average, 8%,4.8%, and 17.8% for heart rate, oxygen saturation, and respiration rate, respectively. It is envisioned that such models could be integrated with monitoring systems that could, using a limited number of vital signs, predict the health conditions of COVID-19 ICU patients in real-time.

Pulmonary vein isolation in a real-world population does not influence QTc interval.

AIMS: We aimed to examine whether routine pulmonary vein isolation (PVI) induces significant ventricular repolarization changes as suggested earlier. METHODS AND RESULTS: Five-minute electrocardiograms were recorded at hospital's admission (T-1d), 1 day after the PVI-procedure (T+1d) and at 3 months post-procedure (T+3m) from a registry of consecutive atrial fibrillation (AF) patients scheduled for routine PVI with different PVI modalities (radiofrequency, cryo-ablation, and hybrid). Only patients who were in sinus rhythm at all three recordings (n = 117) were included. QT-intervals and QT-dispersion were evaluated with custom-made software and QTc was calculated using Bazett's, Fridericia's, Framingham's, and Hodges' formulas. Both QT- and RR-intervals were significantly shorter at T+1d (399 ± 37 and 870 ± 141 ms) and T+3m (407 ± 36 and 950 ± 140 ms) compared with baseline (417 ± 36 and 1025 ± 164 ms). There was no statistically significant within-subject difference in QTc Fridericia (T-1d 416 ± 28 ms, T+1d 419 ± 33 ms, and T+3m 414 ± 25 ms) and QT-dispersion (T-1d 18 ± 12 ms, T+1d 21 ± 19 ms, and T+3m 17 ± 12 ms) between the recordings. A multiple linear regression model with age, sex, AF type, ablation technique, first/re-do ablation, and AF recurrence to predict the change in QTc at T+3m with respect to QTc at T-1d did not reach significance which indicates that the change in QTc does not differ between all subgroups (age, sex, AF type, ablation technique, first/re-do ablation, and AF recurrence). CONCLUSION: Based on our data a routine PVI does not result in a prolongation of QTc in a real-world population. These findings, therefore, suggest that there is no need to intensify post-PVI QT-interval monitoring.

Incidence, prevalence, and trajectories of repetitive conduction patterns in human atrial fibrillation.

AIMS: Repetitive conduction patterns in atrial fibrillation (AF) may reflect anatomical structures harbouring preferential conduction paths and indicate the presence of stationary sources for AF. Recently, we demonstrated a novel technique to detect repetitive patterns in high-density contact mapping of AF. As a first step towards repetitive pattern mapping to guide AF ablation, we determined the incidence, prevalence, and trajectories of repetitive conduction patterns in epicardial contact mapping of paroxysmal and persistent AF patients. METHODS AND RESULTS: A 256-channel mapping array was used to record epicardial left and right AF electrograms in persistent AF (persAF, n = 9) and paroxysmal AF (pAF, n = 11) patients. Intervals containing repetitive conduction patterns were detected using recurrence plots. Activation movies, preferential conduction direction, and average activation sequence were used to characterize and classify conduction patterns. Repetitive patterns were identified in 33/40 recordings. Repetitive patterns were more prevalent in pAF compared with persAF [pAF: median 59%, inter-quartile range (41-72) vs. persAF: 39% (0-51), P < 0.01], larger [pAF: = 1.54 (1.15-1.96) vs. persAF: 1.16 (0.74-1.56) cm2, P < 0.001), and more stable [normalized preferentiality (0-1) pAF: 0.38 (0.25-0.50) vs. persAF: 0.23 (0-0.33), P < 0.01]. Most repetitive patterns were peripheral waves (87%), often with conduction block (69%), while breakthroughs (9%) and re-entries (2%) occurred less frequently. CONCLUSION: High-density epicardial contact mapping in AF patients reveals frequent repetitive conduction patterns. In persistent AF patients, repetitive patterns were less frequent, smaller, and more variable than in paroxysmal AF patients. Future research should elucidate whether these patterns can help in finding AF ablation targets.

Ten-year follow-up after endocardial point-by-point cryoablation for paroxysmal atrial fibrillation.

BACKGROUND: Since many years catheter ablation is widely used for the treatment of atrial fibrillation (AF), however, long-term follow-up data of ablation techniques are rare. This study presents a 10-year follow-up period in patients treated for paroxysmal AF (PAF) with point-by-point pulmonary vein isolation (PVI) using cryothermal energy (cryoPVI). The main objective is to investigate whether cryoPVI is able to create durable PVI. METHODS: All consecutive patients with PAF who underwent a point-by-point cryoPVI were included. Information from the index procedure, anti-arrhythmic drug (AAD) use, recurrence of arrhythmias and re-ablation, was retrospectively analysed. Re-ablations were specifically evaluated for reconnection of PVs. RESULTS: Seventy-three patients were included. Five (7%) were lost to follow-up and 55/73 (75%) reached 10-year follow-up (median follow-up duration: 11.3 years [10.0-12.4]). Thirteen (18%) did not reach 10-years follow-up (mean follow-up duration: 4.4 ± 3.3 years). All targeted PVs were successfully isolated during the index procedure. Only 10/68 patients (15%) kept sinus rhythm (SR) without the use of AAD or a re-ablation. Re-ablations were performed in 47/68 patients (69%). Reconnection was seen in 81% of the PVs. CONCLUSIONS: Ostial point-by-point cryoPVI has the ability to provide acute electrical isolation of arrhythmogenic PVs based on abolition of all PV potentials, but fails in long-term isolation and prevention of AF-recurrence in most patients.

Adenosine usage during AF ablation in Europe and selected long-term findings from the ESC-EHRA EORP Atrial Fibrillation Ablation Long-Term registry.

BACKGROUND: Adenosine can be used to reveal dormant pulmonary vein (PV) conduction after PV isolation (PVI). This study presents a subanalysis of real-world 1-year follow-up data from the ESC-EHRA EORP Atrial Fibrillation (AF) Ablation Long-Term registry to analyze the usage of adenosine during PVI treatment in terms of rhythm outcome and safety. METHODS: The registry consists of 104 participating centers in 27 countries within the European Society of Cardiology. The registry data was split into an adenosine group (AG) and no-adenosine group (NAG). Procedure characteristics and patient outcome were compared. RESULTS: Adenosine was administered in 10.8% of the 3591 PVI patients included in the registry. Spain, the Netherlands, and Italy included the majority of adenosine cases (48.8%). Adenosine was applied more often in combination with open irrigation radiofrequency (RF) energy (74.7%) and less often in combination with nonirrigated RF energy (1.6%). After 1 year, a higher percentage of the AG was free from AF compared with the NAG (68.9% vs 59.1%, p < 0.001). Adenosine was associated with better rhythm outcome in RF ablation procedures, but not in cryo-ablation procedures (freedom from AF: RF: AG: 70.9%, NAG: 58.1%, p < 0.001, cryo: AG: 63.9%, NAG: 63.8%, p = 0.991). CONCLUSIONS: The use of adenosine was associated with a better rhythm outcome after 1 year follow-up and seems more useful in patients treated with RF energy compared with patients treated with cryo energy. Given the improved rhythm outcome at 1-year follow-up, it seems reasonable to encourage the use of adenosine during RF AF ablation.

A Novel Tool for the Identification and Characterization of Repetitive Patterns in High-Density Contact Mapping of Atrial Fibrillation.

INTRODUCTION: Electrical contact mapping provides a detailed view of conduction patterns in the atria during atrial fibrillation (AF). Identification of repetitive wave front propagation mechanisms potentially initiating or sustaining AF might provide more insights into temporal and spatial distribution of candidate AF mechanism and identify targets for catheter ablation. We developed a novel tool based on recurrence plots to automatically identify and characterize repetitive conduction patterns in high-density contact mapping of AF. MATERIALS AND METHODS: Recurrence plots were constructed by first transforming atrial electrograms recorded by a multi-electrode array to activation-phase signals and then quantifying the degree of similarity between snapshots of the activation-phase in the electrode array. An AF cycle length dependent distance threshold was applied to discriminate between repetitive and non-repetitive snapshots. Intervals containing repetitive conduction patterns were detected in a recurrence plot as regions with a high recurrence rate. Intervals that contained similar repetitive patterns were then grouped into clusters. To demonstrate the ability to detect and quantify the incidence, duration and size of repetitive patterns, the tool was applied to left and right atrial recordings in a goat model of different duration of persistent AF [3 weeks AF (3 wkAF, n = 8) and 22 weeks AF (22 wkAF, n = 8)], using a 249-electrode mapping array (2.4 mm inter-electrode distance). RESULTS: Recurrence plots identified frequent recurrences of activation patterns in all recordings and indicated a strong correlation between recurrence plot threshold and AF cycle length. Prolonged AF duration was associated with shorter repetitive pattern duration [mean maximum duration 3 wkAF: 74 cycles, 95% confidence interval (54-94) vs. 22 wkAF: 41 cycles (21-62), p = 0.03], and smaller recurrent regions within repetitive patterns [3 wkAF 1.7 cm2 (1.0-2.3) vs. 22 wkAF 0.5 cm2 (0.0-1.2), p = 0.02]. Both breakthrough patterns and re-entry were identified as repetitive conduction patterns. CONCLUSION: Recurrence plots provide a novel way to delineate high-density contact mapping of AF. Dominant repetitive conduction patterns were identified in a goat model of sustained AF. Application of the developed methodology using the new generation of multi-electrode catheters could identify additional targets for catheter ablation of AF.