Semaglutide and Diuretic Use in Obesity-Related Heart Failure with Preserved Ejection Fraction: A Pooled Analysis of the STEP-HFpEF and STEP-HFpEF-DM trials.

BACKGROUND AND AIMS: In the STEP-HFpEF trial program, treatment with semaglutide resulted in multiple beneficial effects in patients with obesity-related heart failure with preserved ejection fraction (HFpEF). Efficacy may vary according to baseline diuretic use, and semaglutide treatment could modify diuretic dose. METHODS: In this pre-specified analysis of pooled data from the STEP-HFpEF and STEP-HFpEF-DM trials (n=1145), which randomized participants with HFpEF and body mass index ≥30 kg/m2 to once weekly semaglutide 2.4 mg or placebo for 52 weeks, we examined whether efficacy and safety endpoints differed by baseline diuretic use, as well as the effect of semaglutide on loop diuretic use and dose changes over the 52-week treatment period. RESULTS: At baseline, across no diuretic (n=220), non-loop diuretic only (n=223), and loop diuretic (<40 [n=219], 40 [n=309], and >40 [n=174] mg/day furosemide-equivalents) groups, there was progressively higher prevalence of hypertension and atrial fibrillation; and severity of obesity and heart failure. Over 52 weeks of treatment, semaglutide had a consistent beneficial effect on change in body weight across diuretic use categories (adjusted mean difference vs. placebo ranged from -8.8% [95% CI -10.3, -6.3] to -6.9% [95% CI -9.1, -4.7] from no diuretics to the highest loop diuretic dose category; interaction P=0.39). Kansas City Cardiomyopathy Questionnaire clinical summary score improvement was greater in patients on loop diuretics compared to those not on loop diuretics (adjusted mean difference vs. placebo: +9.3 [6.5; 12.1] vs. +4.7 points [1.3, 8.2]; P=0.042). Semaglutide had consistent beneficial effects on all secondary efficacy endpoints (including 6-min walk distance) across diuretic subgroups (interaction P=0.24-0.92). Safety also favored semaglutide versus placebo across the diuretic subgroups. From baseline to 52 weeks, loop diuretic dose decreased by 17% in the semaglutide group vs. a 2.4% increase in the placebo group (P<0.0001). Semaglutide (vs. placebo) was more likely to result in loop diuretic dose reduction (odds ratio [OR] 2.67 [95% CI 1.70, 4.18]) and less likely dose increase (OR 0.35 [95% CI 0.23, 0.53]; P<0.001 for both) from baseline to 52 weeks. CONCLUSIONS: In patients with obesity-related HFpEF, semaglutide improved heart failure-related symptoms and physical limitations across diuretic use subgroups, with more pronounced benefits among patients receiving loop diuretics at baseline. Reductions in weight and improvements in exercise function with semaglutide versus placebo were consistent in all diuretic use categories. Semaglutide also led to a reduction in loop diuretic use and dose between baseline and 52 weeks. CLINICALTRIALS.GOV REGISTRATION: NCT04788511 and NCT04916470.

Semaglutide versus placebo in people with obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF DM randomised trials.

BACKGROUND: In the STEP-HFpEF (NCT04788511) and STEP-HFpEF DM (NCT04916470) trials, the GLP-1 receptor agonist semaglutide improved symptoms, physical limitations, bodyweight, and exercise function in people with obesity-related heart failure with preserved ejection fraction. In this prespecified pooled analysis of the STEP-HFpEF and STEP-HFpEF DM trials, we aimed to provide a more definitive assessment of the effects of semaglutide across a range of outcomes and to test whether these effects were consistent across key patient subgroups. METHODS: We conducted a prespecified pooled analysis of individual patient data from STEP-HFpEF and STEP-HFpEF DM, randomised, double-blind, placebo-controlled trials at 129 clinical research sites in 18 countries. In both trials, eligible participants were aged 18 years or older, had heart failure with a left ventricular ejection fraction of at least 45%, a BMI of at least 30 kg/m2, New York Heart Association class II-IV symptoms, and a Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS; a measure of heart failure-related symptoms and physical limitations) of less than 90 points. In STEP-HFpEF, people with diabetes or glycated haemoglobin A1c concentrations of at least 6·5% were excluded, whereas for inclusion in STEP-HFpEF DM participants had to have been diagnosed with type 2 diabetes at least 90 days before screening and to have an HbA1c of 10% or lower. In both trials, participants were randomly assigned to either 2·4 mg semaglutide once weekly or matched placebo for 52 weeks. The dual primary endpoints were change from baseline to week 52 in KCCQ-CSS and bodyweight in all randomly assigned participants. Confirmatory secondary endpoints included change from baseline to week 52 in 6-min walk distance, a hierarchical composite endpoint (all-cause death, heart failure events, and differences in changes in KCCQ-CSS and 6-min walk distance); and C-reactive protein (CRP) concentrations. Heterogeneity in treatment effects was assessed across subgroups of interest. We assessed safety in all participants who received at least one dose of study drug. FINDINGS: Between March 19, 2021 and March 9, 2022, 529 people were randomly assigned in STEP-HFpEF, and between June 27, 2021 and Sept 2, 2022, 616 were randomly assigned in STEP-HFpEF DM. Overall, 1145 were included in our pooled analysis, 573 in the semaglutide group and 572 in the placebo group. Improvements in KCCQ-CSS and reductions in bodyweight between baseline and week 52 were significantly greater in the semaglutide group than in the placebo group (mean between-group difference for the change from baseline to week 52 in KCCQ-CSS 7·5 points [95% CI 5·3 to 9·8]; p<0·0001; mean between-group difference in bodyweight at week 52 -8·4% [-9·2 to -7·5]; p<0·0001). For the confirmatory secondary endpoints, 6-min walk distance (mean between-group difference at week 52 17·1 metres [9·2 to 25·0]) and the hierarchical composite endpoint (win ratio 1·65 [1·42 to 1·91]) were significantly improved, and CRP concentrations (treatment ratio 0·64 [0·56 to 0·72]) were significantly reduced, in the semaglutide group compared with the placebo group (p<0·0001 for all comparisons). For the dual primary endpoints, the efficacy of semaglutide was largely consistent across multiple subgroups, including those defined by age, race, sex, BMI, systolic blood pressure, baseline CRP, and left ventricular ejection fraction. 161 serious adverse events were reported in the semaglutide group compared with 301 in the placebo group. INTERPRETATION: In this prespecified pooled analysis of the STEP-HFpEF and STEP-HFpEF DM trials, semaglutide was superior to placebo in improving heart failure-related symptoms and physical limitations, and reducing bodyweight in participants with obesity-related heart failure with preserved ejection fraction. These effects were largely consistent across patient demographic and clinical characteristics. Semaglutide was well tolerated. FUNDING: Novo Nordisk.

Wireless continuous single-lead ST-segment monitoring to detect new-onset myocardial injury at the general ward-An exploratory subanalysis.

Patients admitted for acute medical conditions and major noncardiac surgery are at risk of myocardial injury. This is frequently asymptomatic, especially in the context of concomitant pain and analgesics, and detection thus relies on cardiac biomarkers. Continuous single-lead ST-segment monitoring from wireless electrocardiogram (ECG) may enable more timely intervention, but criteria for alerts need to be defined to reduce false alerts. This study aimed to determine optimal ST-deviation thresholds from wireless single-lead ECG for detection of myocardial injury following major abdominal cancer surgery and during acute exacerbation of chronic obstructive pulmonary disease. Patients were monitored with a wireless single-lead ECG patch for up to 4 days and had daily troponin measurements. Single-lead ST-segment deviations of <0.255 mV and/or >0.245 mV (based on previous study comparison with 0.1 mV 12-lead ECG and variation in single-lead ECG) were analyzed for relation to myocardial injury defined as hsTnT elevation of 20-64 ng/L with an absolute change of ≥5 ng/L, or a hsTnT level ≥ 65 ng/L. In total, 528 patients were included for analysis, of which 15.5% had myocardial injury. For corrected ST-thresholds lasting ≥10 and ≥ 20 min, we found specificities of 91% and 94% and sensitivities of 17% and 13% with odds ratios of 2.0 (95% CI: 1.1; 3.9) and 2.4 (95% CI: 1.1; 5.1) for myocardial injury. In conclusion, wireless single-lead ECG monitoring with corrected ST thresholds detected patients developing myocardial injury with specificities >90% and sensitivities <20%, suggesting increased focus on sensitivity improvement.

Probing Activation and Conformational Dynamics of the Vesicle-Reconstituted ß2 Adrenergic Receptor at the Single-Molecule Level.

G-protein-coupled receptors (GPCRs) are structurally flexible membrane proteins that mediate a host of physiological responses to extracellular ligands like hormones and neurotransmitters. Fine features of their dynamic structural behavior are hypothesized to encode the functional plasticity seen in GPCR activity, where ligands with different efficacies can direct the same receptor toward different signaling phenotypes. Although the number of GPCR crystal structures is increasing, the receptors are characterized by complex and poorly understood conformational landscapes. Therefore, we employed a fluorescence microscopy assay to monitor conformational dynamics of single ß2 adrenergic receptors (ß2ARs). To increase the biological relevance of our findings, we decided not to reconstitute the receptor in detergent micelles but rather lipid membranes as proteoliposomes. The conformational dynamics were monitored by changes in the intensity of an environmentally sensitive boron-dipyrromethene (BODIPY 493/503) fluorophore conjugated to an endogenous cysteine (located at the cytoplasmic end of the sixth transmembrane helix of the receptor). Using total internal reflection fluorescence microscopy (TIRFM) and a single small unilamellar liposome assay that we previously developed, we followed the real-time dynamic properties of hundreds of single ß2ARs reconstituted in a native-like environment─lipid membranes. Our results showed that ß2AR-BODIPY fluctuates between several states of different intensity on a time scale of seconds, compared to BODIPY-lipid conjugates that show almost entirely stable fluorescence emission in the absence and presence of the full agonist BI-167107. Agonist stimulation changes the ß2AR dynamics, increasing the population of states with higher intensities and prolonging their durations, consistent with bulk experiments. The transition density plot demonstrates that ß2AR-BODIPY, in the absence of the full agonist, interconverts between states of low and moderate intensity, while the full agonist renders transitions between moderate and high-intensity states more probable. This redistribution is consistent with a mechanism of conformational selection and is a promising first step toward characterizing the conformational dynamics of GPCRs embedded in a lipid bilayer.

Asthma and exercise-induced bronchoconstriction in athletes: Diagnosis, treatment, and anti-doping challenges.

Athletes often experience lower airway dysfunction, such as asthma and exercise-induced bronchoconstriction (EIB), which affects more than half the athletes in some sports, not least in endurance sports. Symptoms include coughing, wheezing, and breathlessness, alongside airway narrowing, hyperresponsiveness, and inflammation. Early diagnosis and management are essential. Not only because untreated or poorly managed asthma and EIB potentially affects competition performance and training, but also because untreated airway inflammation can result in airway epithelial damage, remodeling, and fibrosis. Asthma and EIB do not hinder performance, as advancements in treatment strategies have made it possible for affected athletes to compete at the highest level. However, practitioners and athletes must ensure that the treatment complies with general guidelines and anti-doping regulations to prevent the risk of a doping sanction because of inadvertently exceeding specified dosing limits. In this review, we describe considerations and challenges in diagnosing and managing athletes with asthma and EIB. We also discuss challenges facing athletes with asthma and EIB, while also being subject to anti-doping regulations.

Effects of Semaglutide on Symptoms, Function, and Quality of Life in Patients With Heart Failure With Preserved Ejection Fraction and Obesity: A Prespecified Analysis of the STEP-HFpEF Trial.

BACKGROUND: Patients with heart failure (HF) with preserved ejection fraction (HFpEF) and obesity experience a high burden of symptoms and functional impairment, and a poor quality of life. In the STEP-HFpEF trial (Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity), once-weekly semaglutide 2.4 mg improved symptoms, physical limitations, and exercise function, and reduced inflammation and body weight. This prespecified analysis investigated the effects of semaglutide on the primary and confirmatory secondary end points across the range of the Kansas City Cardiomyopathy Questionnaire (KCCQ) scores at baseline and on all key summary and individual KCCQ domains. METHODS: STEP-HFpEF randomly assigned 529 participants with symptomatic HF, an ejection fraction of ≥45%, and a body mass index of ≥30 kg/m2 to once-weekly semaglutide 2.4 mg or placebo for 52 weeks. Dual primary end points change in KCCQ-Clinical Summary Score (CSS) and body weight. Confirmatory secondary end points included change in 6-minute walk distance, a hierarchical composite end point (death, HF events, and change in KCCQ-CSS and 6-minute walk distance) and change in C-reactive protein. Patients were stratified by KCCQ-CSS tertiles at baseline. Semaglutide effects on the primary, confirmatory secondary, and select exploratory end points (N-terminal pro-brain natriuretic peptide) were examined across these subgroups. Semaglutide effects on additional KCCQ domains (Total Symptom Score [including symptom burden and frequency], Physical Limitations Score, Social Limitations Score, Quality of Life Score, and Overall Summary Score) were also evaluated. RESULTS: Baseline median KCCQ-CSS across tertiles was 37, 59, and 77 points, respectively. Semaglutide consistently improved primary end points across KCCQ tertiles 1 to 3 (estimated treatment differences [95% CI]: for KCCQ-CSS, 10.7 [5.4 to 16.1], 8.1 [2.7 to 13.4], and 4.6 [-0.6 to 9.9] points; for body weight, -11 [-13.2 to -8.8], -9.4 [-11.5 to -7.2], and -11.8 [-14.0 to -9.6], respectively; Pinteraction=0.28 and 0.29, respectively); the same was observed for confirmatory secondary and exploratory end points (Pinteraction>0.1 for all). Semaglutide-treated patients experienced improvements in all key KCCQ domains (estimated treatment differences, 6.7-9.6 points across domains; P≤0.001 for all). Greater proportion of semaglutide-treated versus placebo-treated patients experienced at least 5-, 10-, 15-, and 20-point improvements in all KCCQ domains (odds ratios, 1.6-2.9 across domains; P<0.05 for all). CONCLUSIONS: In patients with HFpEF and obesity, semaglutide produced large improvements in HF-related symptoms, physical limitations, exercise function, inflammation, body weight, and N-terminal pro-brain natriuretic peptide, regardless of baseline health status. The benefits of semaglutide extended to all key KCCQ domains. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04788511.

The effect of technical filtering and clinical criteria on alert rates from continuous vital sign monitoring in the general ward.

OBJECTIVES: Continuous vital sign monitoring at the general hospital ward has major potential advantages over intermittent monitoring but generates many alerts with risk of alert fatigue. We hypothesized that the number of alerts would decrease using different filters. METHODS: This study was an exploratory analysis of the alert reducing effect from adding two different filters to continuously collected vital sign data (peripheral oxygen saturation, blood pressure, heart rate, and respiratory rate) in patients admitted after major surgery or severe medical disease. Filtered data were compared to data without artifact removal. Filter one consists of artifact removal, filter two consists of artifact removal plus duration criteria adjusted for severity of vital sign deviation. Alert thresholds were based on the National Early Warning Score (NEWS) threshold. RESULTS: A population of 716 patients admitted for severe medical disease or major surgery with continuous wireless vital sign monitoring at the general ward with a mean monitoring time of 75.8 h, were included for the analysis. Without artifact removal, we found a median of 137 [IQR: 87-188] alerts per patient/day, artifact removal resulted in a median of 101 [IQR: 56-160] alerts per patient/day and with artifact removal combined with a duration-severity criterion, we found a median of 19 [IQR: 9-34] alerts per patient/day. Reduction of alerts was 86.4% (p < 0.001) for values without artifact removal (137 alerts) vs. the duration criteria and a reduction (19 alerts) of 81.5% (p < 0.001) for the criteria with artifact removal (101 alerts) vs. the duration criteria (19 alerts). CONCLUSION: We conclude that a combination of artifact removal and duration-severity criteria approach substantially reduces alerts generated by continuous vital sign monitoring.

Semaglutide in Patients With Obesity and Heart Failure Across Mildly Reduced or Preserved Ejection Fraction.

BACKGROUND: Many therapies for heart failure (HF) have shown differential impact across the spectrum of left ventricular ejection fraction (LVEF). OBJECTIVES: In this prespecified analysis, the authors assessed the effects of semaglutide across the baseline LVEF strata in patients with the obesity phenotype of HF with preserved ejection fraction (HFpEF) in the STEP-HFpEF (Semaglutide Treatment Effect in People with obesity and HFpEF) trial. METHODS: STEP-HFpEF randomized 529 patients (263 semaglutide; 266 placebo). For this prespecified analysis, patients were categorized into 3 groups based on LVEF: 45% to 49% (n = 85), 50% to 59% (n = 215), and ≥60% (n = 229). RESULTS: At 52 weeks, semaglutide improved the dual primary endpoints of Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (estimated treatment difference: EF [ejection fraction] 45%-49%: 5.0 points [95% CI: -2.7 to 12.8 points], EF 50%-59%: 9.8 points [95% CI: 5.0 to 14.6 points], and EF ≥60%: 7.4 points [95% CI: 2.8 to 12.0 points]; P interaction = 0.56) and body weight (EF: 45%-49%: -7.6 [95% CI: -10.7 to -4.4], EF 50%-59%: -10.6 [95% CI: -12.6 to -8.6] and EF ≥60%: -11.9 [95% CI: -13.8 to -9.9]; P interaction = 0.08), to a similar extent across LVEF categories. Likewise, LVEF did not influence the benefit of semaglutide on confirmatory secondary endpoints: 6-minute walk distance (P interaction = 0.19), hierarchal composite endpoint (P interaction = 0.43), and high-sensitivity C-reactive protein (P interaction = 0.26); or exploratory endpoint of N-terminal pro-brain natriuretic peptide (P interaction = 0.96). Semaglutide was well-tolerated across LVEF categories. CONCLUSIONS: In patients with HFpEF and obesity, semaglutide 2.4 mg improved symptoms, physical limitations, and exercise function, and reduced inflammation and body weight to a similar extent across LVEF categories. These data support treatment with semaglutide in patients with the obesity phenotype of HFpEF regardless of LVEF. (Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity [STEP-HFpEF]; NCT04788511).

Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity.

BACKGROUND: Heart failure with preserved ejection fraction is increasing in prevalence and is associated with a high symptom burden and functional impairment, especially in persons with obesity. No therapies have been approved to target obesity-related heart failure with preserved ejection fraction. METHODS: We randomly assigned 529 patients who had heart failure with preserved ejection fraction and a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or higher to receive once-weekly semaglutide (2.4 mg) or placebo for 52 weeks. The dual primary end points were the change from baseline in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS; scores range from 0 to 100, with higher scores indicating fewer symptoms and physical limitations) and the change in body weight. Confirmatory secondary end points included the change in the 6-minute walk distance; a hierarchical composite end point that included death, heart failure events, and differences in the change in the KCCQ-CSS and 6-minute walk distance; and the change in the C-reactive protein (CRP) level. RESULTS: The mean change in the KCCQ-CSS was 16.6 points with semaglutide and 8.7 points with placebo (estimated difference, 7.8 points; 95% confidence interval [CI], 4.8 to 10.9; P<0.001), and the mean percentage change in body weight was -13.3% with semaglutide and -2.6% with placebo (estimated difference, -10.7 percentage points; 95% CI, -11.9 to -9.4; P<0.001). The mean change in the 6-minute walk distance was 21.5 m with semaglutide and 1.2 m with placebo (estimated difference, 20.3 m; 95% CI, 8.6 to 32.1; P<0.001). In the analysis of the hierarchical composite end point, semaglutide produced more wins than placebo (win ratio, 1.72; 95% CI, 1.37 to 2.15; P<0.001). The mean percentage change in the CRP level was -43.5% with semaglutide and -7.3% with placebo (estimated treatment ratio, 0.61; 95% CI, 0.51 to 0.72; P<0.001). Serious adverse events were reported in 35 participants (13.3%) in the semaglutide group and 71 (26.7%) in the placebo group. CONCLUSIONS: In patients with heart failure with preserved ejection fraction and obesity, treatment with semaglutide (2.4 mg) led to larger reductions in symptoms and physical limitations, greater improvements in exercise function, and greater weight loss than placebo. (Funded by Novo Nordisk; STEP-HFpEF ClinicalTrials.gov number, NCT04788511.).

Effect of semaglutide on major adverse cardiovascular events by baseline kidney parameters in participants with type 2 diabetes and at high risk of cardiovascular disease: SUSTAIN 6 and PIONEER 6 post hoc pooled analysis.

BACKGROUND: Semaglutide is a glucose-lowering treatment for type 2 diabetes (T2D) with demonstrated cardiovascular benefits; semaglutide may also have kidney-protective effects. This post hoc analysis investigated the association between major adverse cardiovascular events (MACE) and baseline kidney parameters and whether the effect of semaglutide on MACE risk was impacted by baseline kidney parameters in people with T2D at high cardiovascular risk. METHODS: Participants from the SUSTAIN 6 and PIONEER 6 trials, receiving semaglutide or placebo, were categorised according to baseline kidney function (estimated glomerular filtration rate [eGFR] < 45 and ≥ 45-<60 versus ≥ 60 mL/min/1.73 m2) or damage (urine albumin:creatinine ratio [UACR] ≥ 30-≤300 and > 300 versus < 30 mg/g). Relative risk of first MACE by baseline kidney parameters was evaluated using a Cox proportional hazards model. The same model, adjusted with inverse probability weighting, and a quadratic spline regression were applied to evaluate the effect of semaglutide on risk and event rate of first MACE across subgroups. The semaglutide effects on glycated haemoglobin (HbA1c), body weight (BW) and serious adverse events (SAEs) across subgroups were also evaluated. RESULTS: Independently of treatment, participants with reduced kidney function (eGFR ≥ 45-<60 and < 45 mL/min/1.73 m2: hazard ratio [95% confidence interval]; 1.36 [1.04;1.76] and 1.52 [1.15;1.99]) and increased albuminuria (UACR ≥ 30-≤300 and > 300 mg/g: 1.53 [1.14;2.04] and 2.52 [1.84;3.42]) had an increased MACE risk versus those without. Semaglutide consistently reduced MACE risk versus placebo across all eGFR and UACR subgroups (interaction p value [pINT] > 0.05). Semaglutide reduced HbA1c regardless of baseline eGFR and UACR (pINT>0.05); reductions in BW were affected by baseline eGFR (pINT<0.001) but not UACR (pINT>0.05). More participants in the lower eGFR or higher UACR subgroups experienced SAEs versus participants in reference groups; the number of SAEs was similar between semaglutide and placebo arms in each subgroup. CONCLUSIONS: MACE risk was greater for participants with kidney impairment or damage than for those without. Semaglutide consistently reduced MACE risk across eGFR and UACR subgroups, indicating that semaglutide provides cardiovascular benefits in people with T2D and at high cardiovascular risk across a broad spectrum of kidney function and damage. TRIAL REGISTRATIONS: NCT01720446; NCT02692716.

OCT or Angiography Guidance for PCI in Complex Bifurcation Lesions.

BACKGROUND: Imaging-guided percutaneous coronary intervention (PCI) is associated with better clinical outcomes than angiography-guided PCI. Whether routine optical coherence tomography (OCT) guidance in PCI of lesions involving coronary-artery branch points (bifurcations) improves clinical outcomes as compared with angiographic guidance is uncertain. METHODS: We conducted a multicenter, randomized, open-label trial at 38 centers in Europe. Patients with a clinical indication for PCI and a complex bifurcation lesion identified by means of coronary angiography were randomly assigned in a 1:1 ratio to OCT-guided PCI or angiography-guided PCI. The primary end point was a composite of major adverse cardiac events (MACE), defined as death from a cardiac cause, target-lesion myocardial infarction, or ischemia-driven target-lesion revascularization at a median follow-up of 2 years. RESULTS: We assigned 1201 patients to OCT-guided PCI (600 patients) or angiography-guided PCI (601 patients). A total of 111 patients (18.5%) in the OCT-guided PCI group and 116 (19.3%) in the angiography-guided PCI group had a bifurcation lesion involving the left main coronary artery. At 2 years, a primary end-point event had occurred in 59 patients (10.1%) in the OCT-guided PCI group and in 83 patients (14.1%) in the angiography-guided PCI group (hazard ratio, 0.70; 95% confidence interval, 0.50 to 0.98; P = 0.035). Procedure-related complications occurred in 41 patients (6.8%) in the OCT-guided PCI group and 34 patients (5.7%) in the angiography-guided PCI group. CONCLUSIONS: Among patients with complex coronary-artery bifurcation lesions, OCT-guided PCI was associated with a lower incidence of MACE at 2 years than angiography-guided PCI. (Funded by Abbott Vascular and others; OCTOBER ClinicalTrials.gov number, NCT03171311.).

Semaglutide in HFpEF across obesity class and by body weight reduction: a prespecified analysis of the STEP-HFpEF trial.

In the STEP-HFpEF trial, semaglutide improved symptoms, physical limitations and exercise function and reduced body weight in patients with obesity phenotype of heart failure and preserved ejection fraction (HFpEF). This prespecified analysis examined the effects of semaglutide on dual primary endpoints (change in Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS) and body weight) and confirmatory secondary endpoints (change in 6-minute walk distance (6MWD), hierarchical composite (death, HF events, change in KCCQ-CSS and 6MWD) and change in C-reactive protein (CRP)) across obesity classes I-III (body mass index (BMI) 30.0-34.9 kg m-2, 35.0-39.9 kg m-2 and ≥40 kg m-2) and according to body weight reduction with semaglutide after 52 weeks. Semaglutide consistently improved all outcomes across obesity categories (P value for treatment effects × BMI interactions = not significant for all). In semaglutide-treated patients, improvements in KCCQ-CSS, 6MWD and CRP were greater with larger body weight reduction (for example, 6.4-point (95% confidence interval (CI): 4.1, 8.8) and 14.4-m (95% CI: 5.5, 23.3) improvements in KCCQ-CSS and 6MWD for each 10% body weight reduction). In participants with obesity phenotype of HFpEF, semaglutide improved symptoms, physical limitations and exercise function and reduced inflammation and body weight across obesity categories. In semaglutide-treated patients, the magnitude of benefit was directly related to the extent of weight loss. Collectively, these data support semaglutide-mediated weight loss as a key treatment strategy in patients with obesity phenotype of HFpEF. ClinicalTrials.gov identifier: NCT04788511 .

Quantifying physiological stability in the general ward using continuous vital signs monitoring: the circadian kernel density estimator.

Technological advances seen in recent years have introduced the possibility of changing the way hospitalized patients are monitored by abolishing the traditional track-and-trigger systems and implementing continuous monitoring using wearable biosensors. However, this new monitoring paradigm raise demand for novel ways of analyzing the data streams in real time. The aim of this study was to design a stability index using kernel density estimation (KDE) fitted to observations of physiological stability incorporating the patients' circadian rhythm. Continuous vital sign data was obtained from two observational studies with 491 postoperative patients and 200 patients with acute exacerbation of chronic obstructive pulmonary disease. We defined physiological stability as the last 24 h prior to discharge. We evaluated the model against periods of eight hours prior to events defined either as severe adverse events (SAE) or as a total score in the early warning score (EWS) protocol of ≥ 6, ≥ 8, or ≥ 10. The results found good discriminative properties between stable physiology and EWS-events (area under the receiver operating characteristics curve (AUROC): 0.772-0.993), but lower for the SAEs (AUROC: 0.594-0.611). The time of early warning for the EWS events were 2.8-5.5 h and 2.5 h for the SAEs. The results showed that for severe deviations in the vital signs, the circadian KDE model can alert multiple hours prior to deviations being noticed by the staff. Furthermore, the model shows good generalizability to another cohort and could be a simple way of continuously assessing patient deterioration in the general ward.

Deviating vital signs in continuous monitoring prior to discharge and risk of readmission: an observational study.

Premature discharge may result in readmission while longer hospitalization may increase risk of complications such as immobilization and reduce hospital capacity. Continuous monitoring detects more deviating vital signs than intermittent measurements and may help identify patients at risk of deterioration after discharge. We aimed to investigate the association between deviating vital signs detected by continuous monitoring prior to discharge and risk of readmission within 30 days. Patients undergoing elective major abdominal surgery or admitted with acute exacerbation of chronic obstructive pulmonary disease were included in this study. Eligible patients had vital signs monitored continuously within the last 24 h prior to discharge. The association between sustained deviated vital signs and readmission risk was analyzed by using Mann-Whitney's U test and Chi-square test. A total of 51 out of 265 patients (19%) were readmitted within 30 days. Deviated respiratory vital signs occurred frequently in both groups: desaturation < 88% for at least ten minutes was seen in 66% of patients who were readmitted and in 62% of those who were not (p = 0.62) while desaturation < 85% for at least five minutes was seen in 58% of readmitted and 52% of non-readmitted patients (p = 0.5). At least one sustained deviated vital sign was detected in 90% and 85% of readmitted patients and non-readmitted patients, respectively (p = 0.2). Deviating vital signs prior to hospital discharge were frequent but not associated with increased risk of readmission within 30 days. Further exploration of deviating vital signs using continuous monitoring is needed.

Deviations in continuously monitored electrodermal activity before severe clinical complications: a clinical prospective observational explorative cohort study.

Monitoring of high-risk patients in hospital wards is crucial in identifying and preventing clinical deterioration. Sympathetic nervous system activity measured continuously and non-invasively by Electrodermal activity (EDA) may relate to complications, but the clinical use remains untested. The aim of this study was to explore associations between deviations of EDA and subsequent serious adverse events (SAE). Patients admitted to general wards after major abdominal cancer surgery or with acute exacerbation of chronic obstructive pulmonary disease were continuously EDA-monitored for up to 5 days. We used time-perspectives consisting of 1, 3, 6, and 12 h of data prior to first SAE or from start of monitoring. We constructed 648 different EDA-derived features to assess EDA. The primary outcome was any SAE and secondary outcomes were respiratory, infectious, and cardiovascular SAEs. Associations were evaluated using logistic regressions with adjustment for relevant confounders. We included 714 patients and found a total of 192 statistically significant associations between EDA-derived features and clinical outcomes. 79% of these associations were EDA-derived features of absolute and relative increases in EDA and 14% were EDA-derived features with normalized EDA above a threshold. The highest F1-scores for primary outcome with the four time-perspectives were 20.7-32.8%, with precision ranging 34.9-38.6%, recall 14.7-29.4%, and specificity 83.1-91.4%. We identified statistically significant associations between specific deviations of EDA and subsequent SAE, and patterns of EDA may be developed to be considered indicators of upcoming clinical deterioration in high-risk patients.

Redox dynamics of 2D crystalline vanadium oxide phases on high-index anatase facets.

Vanadium oxides exist in a multitude of phases with varying structure and stoichiometry. This abundance of phases can be extended through the use of other oxides as supports, and through redox treatments. However, the combined effects of different supports and redox treatments can be difficult to identify, particularly when present as different terminating facets on nanoparticles. Here, we examine structural dynamics of 2D vanadium oxides supported on anatase TiO2 nanoparticles, correlated with changes in oxidation state, using in situ transmission electron microscopy imaging and electron energy loss spectroscopy. As the average oxidation state is reduced below V(IV), an ordered cubic V(II) phase is observed exclusively at the high-index {10l} facets of the support. This local accommodation of highly reduced states is necessary for explaining the observed range of average oxidation states. In turn, the findings show that oxidation states extending from V(V)-V(IV) to V(II) can be simultaneously stabilized by different supporting oxide surfaces during exposure to atmospheres with controlled redox potential.