Citations

Abstract Atrial fibrillation (AF) is increasingly diagnosed early, close to its first occurrence due to: (i) increased public awareness with self-screening; (ii) health care initiatives including population screening and opportunistic case finding; and (iii) increased use and surveillance of implantable cardiac devices. At its onset, AF is often low burden, and cardiovascular co-morbidities may be absent or at an early stage. Thus, the management of recent-onset AF has become an issue of growing importance. Professional guidelines have traditionally focused on anticoagulant thromboprophylaxis, generally recommending a cautious approach to rhythm control, and priority has been given to rate control to alleviate symptoms. In recent guidelines, the importance of managing lifestyle and co-morbidities has increased. The AF-SCREEN collaboration proposes that a vigorous approach to active management of recent-onset AF may be warranted. This includes addressing co-morbidities and promoting healthy lifestyles to prevent the emergence or progression of AF and associated cardiovascular disease, as well as the initiation of active rhythm control ± anticoagulation to prevent AF-related morbidity and mortality, including stroke and heart failure (HF). Intuitively, intervention early after AF onset would be beneficial since lifestyle and co-morbidity management, plus rhythm control and anticoagulation, are important contributors to improved outcomes in patients with established AF, but robust evidence is lacking for recent-onset AF. There is a delicate balance between achieving favourable outcomes such as preventing strokes, HF and AF progression vs the complications and potential adverse effects of interventions. Given the serious long-term consequences, innovative approaches are necessary to determine the value and risks of initiating active therapy very early in the course of AF. More data are needed to guide the best management of recent-onset AF, bearing AF burden in mind. Long-term studies using large national databases linked to electronic medical records and rhythm monitoring devices offer excellent opportunities. Shorter-term studies focusing on reducing AF burden to slow AF progression and studies focusing on outcomes such as HF could be used in both randomized clinical trials and observational cohort studies.

Background: ECG interpretation is crucial in medical practice, but professionals struggle with achieving and maintaining competency. Identifying proficiency gaps aids in designing educational interventions. Methods: Medical professionals from various disciplines interpreted 30 12-lead ECGs containing commonly taught urgent and non-urgent findings. Performance metrics evaluated were overall adjusted score (% of correctly identified findings using a point-value score based on clinical relevance), unadjusted score (% of correctly identified findings), interpretation time per ECG, and self-reported confidence (rated on an ordinal scale of 0 [not confident], 1 [somewhat confident], or 2 [confident]). Results: Among 1206 participants, there were 72 (6%) primary care physicians (PCPs), 146 (12%) cardiology fellows-in-training (FIT), 353 (29%) resident physicians, 182 (15%) medical students, 84 (7%) advanced practice providers (APPs), 120 (10%) nurses, 249 (21%) allied health professionals, 571 (47%) physicians, and 453 (38%) non-physicians. Participants had a mean adjusted score of 46.9% (± 15.9%), unadjusted score of 56.4% (± 17.2%), interpretation time of 142 seconds (± 67 seconds), and confidence of 0.83 (± 0.53) (Table 1) . Performance varied across groups; cardiology FIT had superior performance in all metrics. Physicians generally outperformed non-physicians, with higher overall adjusted score (52% vs. 43%; p<0.01), unadjusted score (62% vs. 52%; p<0.01), and confidence (0.91 vs. 0.80; p<0.01). Unadjusted score for PCPs was higher than nurses and APPs (58% vs. 47% and 51%; p<0.01) but lower than resident physicians (58% vs. 60%; p<0.01). Allied health professionals outperformed nurses and APPs and closely matched resident physicians and PCPs. Conclusions: Significant gaps in ECG interpretation proficiency exist, emphasizing the need for comprehensive, scalable, and accessible educational tools.

Abstract We aim to provide a critical appraisal of basic concepts underlying signal recording and processing technologies applied for (i) atrial fibrillation (AF) mapping to unravel AF mechanisms and/or identifying target sites for AF therapy and (ii) AF detection, to optimize usage of technologies, stimulate research aimed at closing knowledge gaps, and developing ideal AF recording and processing technologies. Recording and processing techniques for assessment of electrical activity during AF essential for diagnosis and guiding ablative therapy including body surface electrocardiograms (ECG) and endo- or epicardial electrograms (EGM) are evaluated. Discussion of (i) differences in uni-, bi-, and multi-polar (omnipolar/Laplacian) recording modes, (ii) impact of recording technologies on EGM morphology, (iii) global or local mapping using various types of EGM involving signal processing techniques including isochronal-, voltage- fractionation-, dipole density-, and rotor mapping, enabling derivation of parameters like atrial rate, entropy, conduction velocity/direction, (iv) value of epicardial and optical mapping, (v) AF detection by cardiac implantable electronic devices containing various detection algorithms applicable to stored EGMs, (vi) contribution of machine learning (ML) to further improvement of signals processing technologies. Recording and processing of EGM (or ECG) are the cornerstones of (body surface) mapping of AF. Currently available AF recording and processing technologies are mainly restricted to specific applications or have technological limitations. Improvements in AF mapping by obtaining highest fidelity source signals (e.g. catheter–electrode combinations) for signal processing (e.g. filtering, digitization, and noise elimination) is of utmost importance. Novel acquisition instruments (multi-polar catheters combined with improved physical modelling and ML techniques) will enable enhanced and automated interpretation of EGM recordings in the near future.

Maternal infection is a risk for preterm delivery. Preterm newborns often require supplemental oxygen to treat neonatal respiratory distress. Newborn hyperoxia exposure is associated with airway and vascular hyperreactivity, while the complications of maternal infection are variable. In a mouse model of prenatal maternal intraperitoneal lipopolysaccharide (LPS, embryonic day 18) with subsequent newborn hyperoxia (40% oxygen × 7 days) precision-cut living lung slices were used to measure intrapulmonary airway and vascular reactivity at 21 days of age. Hyperoxia increased airway reactivity to methacholine compared to room air controls. Prenatal maternal LPS did not alter airway reactivity in room air. Combined maternal LPS and hyperoxia exposures increased airway reactivity vs. controls, although maximal responses were diminished compared to hyperoxia alone. Vessel reactivity to serotonin did not significantly differ in hyperoxia or room air; however, prenatal maternal LPS appeared to attenuate vessel reactivity in room air. Following room air recovery, LPS with hyperoxia lungs displayed upregulated inflammatory and fibrosis genes compared to room air saline controls (TNFαR1, iNOS, and TGFβ). In this model, mild newborn hyperoxia increases airway but not vessel reactivity. Prenatal maternal LPS did not further increase hyperoxic airway reactivity. However, inflammatory genes remain upregulated weeks after recovery from maternal LPS and newborn hyperoxia exposures.

Supplemental O 2 is a primary mode of respiratory therapy for preterm infants. Numerous studies, however, have shown that supplemental O 2 may contribute to the pathophysiology of airway hyperreactivity (AHR) associated with wheezing disorders such as asthma later in childhood. The calcium‐sensitive receptor (CaSR) is a potent modulator of smooth muscle contractility and may be an underlying feature of childhood asthma. In the present study, we investigated whether CaSR is involved in neonatal hyperoxia induced AHR in a mouse model of BPD. We hypothesize that inhibition (CaSR antagonism), downregulation of expression (siRNA), or deletion (CaSR KO mice) of CaSR will attenuate the AHR induced by hyperoxia in neonatal mice. Newborn C57BL/6 wild‐type (background) or CaSR −/− (knockout) mice were randomized on the second day of life and assigned to room air (21% O 2 ) or hyperoxic (40% O 2 ) groups and exposed for seven days, then recovered in room air for two additional weeks. At day P21, AHR was assessed in vitro using precision‐cut living lung slice preparations in response to increasing doses of methacholine (MCh, 0.25–8 μM). Wild‐type lung slices were pre‐incubated for 48 h in a CaSR siRNA sequence (40 nM) or scrambled RNA as a negative control. In another set of experiments, slices were pre‐incubated in a CaSR antagonist – NPS 2143 (10 nM) for 1 h. Airways were imaged and airway reactivity was expressed as percent change from baseline airway lumen area (± SEM). Neonatal hyperoxia significantly increased airway contractile responses to MCh in wild‐type mice with a mean maximal effect (Emax) of 68.4±8.7% decrease in airway lumen area compared to room air controls (47.3±5.8%, p<0.001), indicating AHR. Pre‐incubation (48hrs) with siRNA targeting CaSR or pharmacologic inhibition (NPS 2143, 1hr incubation) of CaSR reversed the hyperoxia‐induced AHR and the contractile responses were normalized to control level, with hyperoxic groups Emax of 44.0±5.2% and 41.3±3.1%, respectively. AHR was not observed in CaSR knockout mice suggesting resistance to hyperoxia exposure. These data suggest that CaSR plays an important role in the long‐term effects of neonatal hyperoxia on AHR. We speculate that CaSR may be a novel therapeutic target to reverse airway hyperreactivity in former preterm infants who had received prior supplemental O 2 therapy. Support or Funding Information Funding: NIH: HL R01 138402 and NIH R01 HL 056470

Continuous positive airway pressure (CPAP) is a common mode of respiratory support for preterm infants. Recent studies from our lab, however, have shown that CPAP may contribute to the pathophysiology of airway hyperreactivity (AHR) associated with wheezing disorders in former preterm infants. The long‐term effects of CPAP on lung‐development, however, still remain largely unknown. Both hyaluronan synthase 3 (HAS3) and the calcium‐sensitive receptor (CaSR) have been associated with various respiratory morbidities. In the present study, we used a neonatal mouse model of daily CPAP treatment to investigate whether the long‐term effects on AHR are associated with changes in airway HAS3 and CaSR expression. Neonatal mice were exposed to CPAP (6cm H 2 O) for 3 hours per day for the first 7 postnatal days. Control animals experienced the same conditions as experimental animals only with no CPAP. On postnatal day 21, the lungs from these animals were harvested for either real time rt‐PCR or immunohistochemistry to assess changes in HAS3 and CaSR expression. We observed increased expression of multiple genes involved in hylauraonan synthesis, most notably has3 , as well as increased CaSR expression, in the lungs of mice two weeks after CPAP ended when compared to control mice. The increased gene expression of has3 and CaSR was also reflected in increased protein expression as confirmed by immunohistochemistry. HAS3 was expressed predominantly in airway epithelium and the increased CaSR expression correlated with increased αSM actin. To further investigate the role of CaSR in CPAP‐induced AHR, CaSR KO mice ( CaSR (−/−) ) were exposed to CPAP and airway reactivity to methacholine challenge was assessed two weeks later (P21 days). Compared to control mice, AHR was not expressed in CaSR (−/−) mice suggesting resistance to CPAP treatment. These data suggest increased airway HAS3 and CaSR may be important modulators of CPAP‐induced AHR and remodeling. Support or Funding Information HLR01138402 HLR01056470