Higher Risk Of Adverse Outcomes Research Articles

Frailty syndrome and end-stage kidney disease outcomes at a Latin American dialysis center.

Frailty syndrome generates a high risk of adverse outcomes and mortality, and its prevalence is elevated in patients with end-stage kidney disease. Few studies have reported the prevalence and outcomes of frailty in populations from less developed countries. To identify the clinical outcomes and factors associated with the frailty syndrome in patients with stage five chronic kidney disease who started renal replacement therapy - both hemodialysis and peritoneal dialysis- in a dialysis center in Bucaramanga, Colombia. This was a prospective study of patients with end-stage kidney disease who initiated dialysis at a center in Colombia and had a twelve-month follow-up. The overall frailty prevalence was 50.47% and two out of three patients older than 65 years had the syndrome. We found significantly higher followup mortality among patients with frailty: odds ratio of 2.95 (CI: 1.07- 8.13; p=0.036) in unadjusted analysis. Literature shows that compared to developed nations, Latin American adults are facing a higher prevalence of chronic diseases, and frailty syndrome is raising. In this study, according to the FRAIL scale, having a frailty syndrome predicts a higher mortality; hypoalbuminemia and low creatinine levels at the beginning of dialysis could act as predictors of its diagnosis.

THE INFLUENCE OF RURALITY AND FRAILTY ON HEALTH OUTCOMES IN OLDER ADULTS

Abstract Background Frailty is a syndrome representing a decline in physical function and an increased vulnerability to stressors. Older adults in rural areas may be at increased risk for frailty and adverse outcomes due to worse overall health. Our aim was to identify how rural/urban residence can influence frailty status. Methods We used National Health and Aging Trend Study (2011-2020) data, a cohort of Medicare beneficiaries. Participants were categorized as robust, pre-frail, and frail (Fried’s frailty phenotype). Rural residence included counties outside of a metropolitan statistical area (Office of Management and Budget). Participants were excluded if frailty components or geographical status were incomplete. We used logistic regression analyses for the relationship between adverse outcomes (death, nursing home placement over 2011-2020), rural/urban, and frailty status. Results Of 7,393 participants (57.2% female), median age range was 75-80 years and 19.4% were rural residents. Rates of robust, pre-frailty, and frailty were 41.4%, 48.4%, and 10.2%, respectively. There was no difference of frailty status by rural status nor was there a frailty x rural interaction. Older adults with pre-frailty (OR=1.18; 1.05-1.34) and frailty (OR=1.01; 0.82-1.24) had higher risk of residing in rural than urban areas. Rural residence (OR=1.75;1.33-2.24), pre-frailty (OR=1.87;1.54-2.28) and frailty (OR=3.62; 2.79-4.71) had higher risk of adverse outcomes. Conclusion Participants with pre-frailty had higher odds of living in a rural area. Similarly, participants in rural areas had higher odds of adverse outcomes. These findings may highlight health care disparities in rural areas and opportunities for system- and individual-level interventions to prevent frailty development.

EFFECTS OF CHILDCARE, WORK, AND CAREGIVING INTENSITY ON MALE AND FEMALE FAMILY CAREGIVERS

Abstract Objectives The Behavioral Risk Factor Surveillance System sampled 54,076 caregivers between 2015 and 2017 providing an opportunity to evaluate risk factors for poor mental and physical health among a representative sample of U.S. adult caregivers. This study aimed to evaluate the impact of childcare, work status, and intensity of caregiving among men and women caring for older adults (n = 17,271). Methods Controlling for sociodemographic factors, separate logistic regression analysis for women and men were carried out to assess the main and interaction effects of childcare, work status, and intensity of caregiving on number of poor mental and physical health days in the last month. Results Intensive caregiving demands had adverse effects on both women and men, but being in the workforce was beneficial to both men and women. Women with children at home reported adverse mental health effects but better physical health, while men with children at home reported adverse physical health effects. For women, the combination of not working, children in the household, and high-intensity caregiving were most detrimental to their mental health. Among men, those not working with children in the household, regardless of caregiving intensity, were at highest risk of adverse mental health effects. Discussion Our findings identify caregivers at high risk of adverse outcomes but also point to the need for more fine-grained analyses of how families negotiate the allocation of childcare, work, and caregiving responsibilities over time.

Afghan Immigrant and Refugee Women’s Satisfaction with Maternity Wards Services in Iran

Background: Pregnant refugee women are considered a vulnerable group. They are at too high risk of adverse outcomes for mother and newborns. This study aimed to determine Afghan immigrant and refugee women’s satisfaction with maternity wards services. Materials and methods: A retrospective study carried out on 317 mothers who had referred for postpartum, or abortion care to health care centers. A researcher-developed questionnaire with 32 questions in six different domains was used the level of satisfaction. Data were analyzed by SPSS software, and Spearman, Mann-Whitney, and Kruskal-Wallis tests. Results: Results showed that the mean age of the participants was 27.55±6.24 years. 50.7% had vaginal delivery. The mean score of verbal (15.73±0.53), physical (13.82±0.47), confidentiality (5.88±0.46), and payment process (4±0) domains of satisfaction was good. There was relationship between age of participants and verbal (r=0.15; p=0.02), physical (r=0.16; p=0.02), and consent on care domains of satisfaction (r=0.17; p=0.01). And the type of delivery was related to the negligence domain (p<0.001). Conclusions: Participants received good respectful care except in negligence and consent on care domains. Specific interventions, or plans appear to be essential to improve all domains of care.

Head-to-head comparison of 19 prediction models for short-term outcome in medical patients in the emergency department: a retrospective study

IntroductionPrediction models for identifying emergency department (ED) patients at high risk of poor outcome are often not externally validated. We aimed to perform a head-to-head comparison of the discriminatory performance of several prediction models in a large cohort of ED patients.MethodsIn this retrospective study, we selected prediction models that aim to predict poor outcome and we included adult medical ED patients. Primary outcome was 31-day mortality, secondary outcomes were 1-day mortality, 7-day mortality, and a composite endpoint of 31-day mortality and admission to intensive care unit (ICU).The discriminatory performance of the prediction models was assessed using an area under the receiver operating characteristic curve (AUC). Finally, the prediction models with the highest performance to predict 31-day mortality were selected to further examine calibration and appropriate clinical cut-off points.ResultsWe included 19 prediction models and applied these to 2185 ED patients. Thirty-one-day mortality was 10.6% (231 patients), 1-day mortality was 1.4%, 7-day mortality was 4.4%, and 331 patients (15.1%) met the composite endpoint. The RISE UP and COPE score showed similar and very good discriminatory performance for 31-day mortality (AUC 0.86), 1-day mortality (AUC 0.87), 7-day mortality (AUC 0.86) and for the composite endpoint (AUC 0.81). Both scores were well calibrated. Almost no patients with RISE UP and COPE scores below 5% had an adverse outcome, while those with scores above 20% were at high risk of adverse outcome. Some of the other prediction models (i.e. APACHE II, NEWS, WPSS, MEWS, EWS and SOFA) showed significantly higher discriminatory performance for 1-day and 7-day mortality than for 31-day mortality.ConclusionsHead-to-head validation of 19 prediction models in medical ED patients showed that the RISE UP and COPE score outperformed other models regarding 31-day mortality.

Early Microbiologic Markers of Pulmonary Tuberculosis Treatment Outcomes.

Rationale: Earlier biomarkers of pulmonary tuberculosis (PTB) treatment outcomes are critical to monitor shortened anti-TB treatment (ATT). Objectives: To identify early microbiologic markers of unfavorable TB treatment outcomes. Methods: We performed a subanalysis of 2 prospective TB cohort studies conducted from 2013 to 2019 in India. We included participants aged ⩾18 years who initiated 6-month ATT for clinically or microbiologically diagnosed drug-sensitive PTB and completed at least one follow-up visit. Sputum specimens were subjected to a baseline Xpert Mycobacterium tuberculosis/rifampin (MTB/RIF) assay, acid-fast bacilli (AFB) microscopy and liquid and solid cultures, and serial AFB microscopy and liquid and solid cultures at weeks 2, 4, and 8. Poisson regression was used to assess the impact of available microbiologic markers (test positivity, smear grade, time to detection, and time to conversion) on a composite outcome of failure, recurrence, or death by 18 months after the end of treatment. Models were adjusted for age, sex, nutritional status, diabetes, smoking, alcohol consumption, and regimen type. Results: Among 1,098 eligible cases, there were 251 (22%) adverse TB treatment outcomes: 127 (51%) treatment failures, 73 (29%) recurrences, and 51 (20%) deaths. The primary outcome was independently associated with the Xpert MTB/RIF assay (medium-positive adjusted incidence rate ratio [aIRR], 1.91; 95% confidence interval [CI], 1.07-3.40; high-positive aIRR, 2.51; 95% CI, 1.41-4.46), positive AFB smear (aIRR, 1.48; 95% CI, 1.06-2.06), and positive liquid culture (aIRR, 1.98; 95% CI, 1.21-3.23) at baseline; Week 2 positive liquid culture (aIRR, 1.47; 95% CI, 1.04-2.09); and Week 8 positive AFB smear (aIRR, 1.63; 95% CI, 1.06-2.50) and positive liquid culture (aIRR, 1.54; 95% CI, 1.07-2.22). There was no evidence of Mycobacterium tuberculosis growth in the Mycobacterium Growth Indicator Tube at Week 4 conferring a higher risk of adverse outcomes (aIRR, 1.25; 95% CI, 0.89-1.75). Conclusions: Our analysis identifies Week 2 respiratory mycobacterial culture as the earliest microbiologic marker of unfavorable PTB treatment outcomes.

Coronary no-reflow and adverse events in patients with acute myocardial infarction after percutaneous coronary intervention with current drug-eluting stents and third-generation P2Y12 inhibitors.

The frequency and prognostic value of coronary no-reflow (CNR) was investigated in studies that have used an outdated reperfusion therapy in terms of stent technology and antithrombotic drugs. We assessed the association of CNR with adverse outcomes in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES) and newer antithrombotic drugs, ticagrelor or prasugrel. This study included 3100 patients with AMI who underwent PCI with current DES and third-generation P2Y12 inhibitors. CNR was defined as Thrombolysis in Myocardial Infarction (TIMI) blood flow grade ≤ 2 at the end of PCI. The primary end point was 1-year incidence of net adverse clinical and cerebral events-a composite end point of death of any cause, myocardial infarction, stroke or major bleeding. CNR was diagnosed in 130 patients (4.2%). The primary end point occurred in 28 patients in the CNR group and 354 patients in the reflow group (cumulative incidence 23.2% and 12.8%; adjusted hazard ratio = 1.53, 95% confidence interval 1.01-2.33; P = 0.049). The 1-year incidences of death or myocardial infarction (14.6% vs. 7.6%; P = 0.003), myocardial infarction (8.8% vs. 3.9%; P = 0.007) and major bleeding (10.9% vs. 5.6%; P = 0.008) were significantly higher in patients with CNR than patients with reflow. The risk of adverse events in patients with CNR was highest within the first 30days after PCI. In patients with AMI undergoing PCI with current DES and third generation P2Y12 receptor inhibitors, CNR was associated with a higher risk of adverse outcomes at 1year.

Sleep-disordered breathing patterns and prognosis in pulmonary arterial hypertension: A cluster analysis of nocturnal cardiorespiratory signals

BackgroundSleep-disordered breathing (SDB) is common among pulmonary arterial hypertension (PAH) patients and has been associated with unfavorable outcomes. This study aims to cluster overnight cardiorespiratory signals to investigate PAH phenotypes and examining their prognostic implications. MethodsIn this retrospective cohort study, we recruited consecutive PAH patients who underwent right heart catheterization and nocturnal cardiorespiratory polygraphy to evaluate SDB. Cluster analysis was employed to classify patients based on their SDB patterns. Cox regression analysis and Kaplan-Meier curves were utilized to assess the association between cluster membership and clinical outcomes. Logistic regression was used to identify risk factors associated with the cluster at higher risk of adverse outcomes. ResultsThe study comprised 386 PAH patients, with a mean age of 44.7 ± 17.0 years, of which 46.6 % were male. Three distinct clusters of PAH patients were identified: Cluster 1 (N = 182) presented with minimal SDB, Cluster 2 (N = 125) displayed obstructive sleep apnea (OSA) without significant hypoxemia, and Cluster 3 (N = 79) exhibited predominantly severe hypoxemic burden along with comorbid OSA. Notably, patients in Cluster 3 had an independent association with an increased risk of clinical worsening (hazard ratio 1.96, 95 % confidence interval [CI] 1.08–3.56, P = 0.027) compared to those in Clusters 1, even after adjusting for common confounders. The rate of clinical worsening for PAH-related events and mortality was higher in Cluster 3 than in Clusters 1 and 2 (26.6 % vs. 12.6 % and 19.2 %, respectively, log-rank P = 0.024). Moreover, the left ventricular mass index was identified as an independent risk factor for Cluster 3 (odds ratios 1.01, 95 % CI 1.00–1.02, P = 0.004). ConclusionsPatients with PAH who have nocturnal hypoxemia and OSA had worse clinical outcomes compared to those with only minimal SDB. Tailored management strategies that address both PAH and nocturnal hypoxemia may be effective in improving clinical outcomes.

Aggression Severity as a Predictor of Mortality in Dementia

ObjectivesIn psychogeriatric units for patients with dementia and behavioral problems, aggression is prevalent. Predictions and timely interventions of aggression are essential to create a safe environment and prevent adverse outcomes. Our study aimed to determine whether aggression severity early during admission to these units could be used as an indicator of adverse outcomes. DesignDuring one year, all aggressive incidents on a psychogeriatric unit were systematically recorded using the Revised Staff Observation of Aggression Scale (SOAS-R). The study investigated the link between the severity of incidents within the first 48 hours of admission and adverse outcomes. Setting and ParticipantsAll patients included in the study were admitted to a psychogeriatric unit for dementia and behavioral problems between November 2020 and October 2021. MethodsThe study population was categorized into groups according to the level of aggression severity during the first 48 hours of admission. The impact of aggression severity on the duration of admission, aggression frequency and severity during admission, medication usage at discharge, discharge destination, and mortality risk were examined. ResultsDuring the initial 2 days of admission, 9 of 88 patients had 1 or more severe aggression incidents. An early manifestation of severe aggression was significantly associated with more incidents during hospitalization, a higher total SOAS-R score, and a sevenfold higher 1-year mortality risk compared with patients who did not or only mildly manifested aggression in the first 48 hours of admission. Conclusions and ImplicationsAn early manifestation of aggression not only poses a direct safety risk to all involved but is also an early indicator of patients at risk for more detrimental outcomes, specifically mortality risk. By identifying patients at higher risk for adverse outcomes early, health care providers can provide preventive or timelier interventions, mitigating the risk of adverse outcomes and optimizing care services.

Circulating growth differentiation factor 11 exacerbates myocardial injury in mice and associates with increased infarct size in humans

Abstract Background The heart rejuvenating effects of circulating growth differentiation factor 11 (GDF11), a TGF-β superfamily member that shares 90% homology with myostatin (MSTN), remains controversial. Here, we aimed to probe the role of GDF11 in acute myocardial infarction (MI), a frequent cause of heart failure and premature death during ageing. Methods Young (3-4 months) and old (22-24 months) C57Bl/6 mice were subjected to either systemic recombinant GDF11 (rGDF11; 0.1 mg/kg BW daily) or control treatment over 30 days before myocardial ischaemia-reperfusion (I/R) injury was induced. Dissected hearts underwent in-depth profiling that ranged from histological workup and the assessment of inflammatory pathways to cardiomyocyte viability testing and IPA-guided -omics. Key regulatory mechanisms were studied in vitro using human adult stromal cardiac-specific mesenchymal cells (cMSCs) and HL-1 cardiomyocytes. By harnessing liquid chromatography–tandem mass spectrometry (LC-MS/MS), plasma levels of GDF11/MSTN were determined in prospectively recruited patients with MI and the independent association with myocardial infarct size was estimated using hierarchical regression models. Results In contrast to endogenous Mstn, myocardial Gdf11 mRNA expression levels declined upon ageing, and were further reduced following I/R injury, suggesting a therapeutic potential of GDF11 signalling in MI. Unexpectedly, boosting systemic Gdf11 by rGDF11 delivery prior to myocardial I/R augmented rather than reduced infarct size in mice irrespective of their age, predominantly by accelerating pro-apoptotic signalling. By applying a targeted transcriptomics approach on dissected hearts subjected to I/R, we identified the mesenchymal marker Nkx2-5 to be blunted upon rGDF11 supplementation, pointing toward a cMSC-mediated mechanism. Accordingly, human cMSCs exposed to high rGDF11 in vitro showed similar reductions in NKX2-5 expression levels, coinciding with diminished anti-apoptotic effects conferred by resident cMSCs on HL-1 cardiomyocytes. Finally, by harnessing a highly-specific LC–MS/MS based assay, we show that in patients with MI receiving contemporary management circulating GDF11 but not MSTN levels inclined with age. Moreover, circulating GDF11 emerged as an independent predictor of myocardial infarct size, as estimated by standardized peak creatine kinase-MB levels. Notably, GDF11 levels were particularly elevated in those at high risk for adverse outcomes following the acute event. Conclusions Our data challenge the initially reported rejuvenating effects of circulating GDF11 and suggest that high levels of systemic GDF11 exacerbate myocardial injury in mice by impinging on the cardioprotective effects of resident cMSCs. Persistently high GDF11 levels during ageing may contribute to the age-dependent loss of endogenous cardioprotective mechanisms and thus poor outcomes post-MI.

Role of liver disease in management and outcomes of european and asian patients with atrial fibrillation: a report from two regional prospective observational AF registries

Abstract Background In patients with atrial fibrillation (AF), the impact of liver disease (LD) on prescription of oral anticoagulant (OAC) therapy and risk of outcomes remains unclear, as well as possible differences between ethnicities. Objective To examine the impact of LD in a large cohort of European and Asian AF patients on OAC prescriptions and the risks of adverse outcomes. Methods AF patients derived from from two large prospective observational AF registries, conducted in Europe and Asia, on the basis of the same electronic case report form. OAC prescription and risk of outcomes was analyzed according to LD at baseline. The primary outcome was the composite of all-cause death and major adverse cardiovascular events (MACEs). Logistic and Cox regression analyses were used to determine associations with LD, and interaction analyses were performed to examine possible differences between European and Asian patients. Results 15,681 patients (mean age 69.0, SD 11.6 years; 38.7% female) were included, with 517 (3.3%) reporting LD. AF patients with LD were more likely permanent AF, symptomatic, higher thromboembolic and bleeding risks, and had higher multimorbidity, frailty and polypharmacy than those without LD. At baseline, AF patients with LD were less prescribed OAC, as well as with NOACs, than those without [Figure 1]. After adjustments, LD was associated with lower OAC prescription (OR 0.67, 95% CI 0.53-0.84) overall. OAC was less likely prescribed in European (OR 0.54, 95% CI 0.40-0.71) than in Asian (OR 0.95, 95% CI 0.66-1.39) patients (pint=0.015). No differences were found regarding prescription of NOACs vs. VKAs [Figure 1]. Adjusted Cox regression found that LD was associated with a higher risk of composite outcome (HR 1.42, 95% CI 1.11-1.81) and MACEs (HR 1.47, 95% CI 1.07-2.02), with no ethnic differences (Pint=0.631 and Pint= 0.495 for composite outcome and MACEs respectively). LD patients not receiving OAC were at higher risk for MACEs occurrence than those prescribed (pint=0.050). No differences were found regarding major bleeding. Conclusions Presence of LD in AF is associated with a lower prescription of OAC, especially amongst European patients. LD is associated with a higher risk for adverse outcomes, especially in those not prescribed with OAC.Figure 1

Prevalence and prognostic impact of myocardial injury following hypertensive crisis

Abstract Background In patients with acute chest pain, hypertensive crisis is a common possible diagnosis. Severe hypertension may even cause elevated levels of cardiac troponin indicating myocardial injury. Whether this biomarker response is linked to poorer outcome is unknown. Methods We included patients presenting to the emergency department with suspected myocardial infarction. In accordance with the 4th definition of myocardial infarction the final diagnosis and main cause of symptoms was adjudicated by two trained cardiologists based on all available clinical, imaging and laboratory data, including high-sensitive troponin T (hs-TnT). Hypertensive crisis was confirmed by the adjudicators if an elevation of systolic blood pressure (>160 mmHg) was detected and after careful review of all available data other differential diagnoses were less likely. Patients were stratified in those with myocardial injury (acute or chronic) based on sex-specific hs-TnT cutoffs or those without. Kaplan-Meier survival analysis were calculated for all-cause mortality and a composite of death, myocardial infarction, revascularization or cardiac rehospitalization. The event-rates during two-year follow-up were compared using the log-rank test. Cox-proportional hazard ratios were calculated for each patient group with adjustment for age and sex for 2-year all-cause mortality. Results Out of 2,565 patients 446 (17.4%) had a final diagnosis of hypertensive crisis. Of these, 213 (47.8%) developed myocardial injury with a baseline hs-TnT of 15.0 (IQR 10.0-22.0) ng/L. Among the remaining 2,119 patients with other diagnoses than hypertensive crisis, 910 (42.9%) showed myocardial injury with a baseline hs-TnT of 28.5 (IQR 17.0-67.2) ng/L. Patients with hypertensive crisis accompanied by myocardial injury were older (76 (IQR 68-82) vs 60 (IQR 52-71) years, p=0.001) and more often female (61.0% vs 39.5%, p=0.001). Among patients with hypertensive crisis, 2-year mortality rates were higher in patients with myocardial injury compared to non-injury. However, compared to patients with myocardial injury due to other causes, hypertensive patients showed significantly better outcome (p=0.027; Figure 1A). This was consistent for the combined clinical endpoint (Figure 1B). Compared to non-injury/non-hypertensive patients, hazard ratio (HR) for all-cause death after 2 years was not significant for non-injury/hypertensive patients (HR 0.52 (95% CI 0.19-1.48), p=0.22), while patients with myocardial injury and hypertensive crises had significantly increased risk of death after 2 years (HR 1.81 (95% CI 1.02-3.22), p=0.044). In patients with myocardial injury caused by other reasons risk of death was even higher (HR 3.58 (95% CI 2.38-5.39), p=0.001). Conclusion Patients with myocardial injury due to hypertensive crisis are at high risk for adverse outcome within 2 years after presentation. However, compared to other reasons for myocardial injury hypertensive crisis seems less hazardous.Figure 1

Meta-analysis of the performances of contemporary risk models in cardiac surgery for infective endocarditis

Abstract Background Risk scores play important roles in the decision-making for cardiac surgery, but remain under-studied in the setting of infective endocarditis (IE) when there is often a high risk of adverse outcomes. Several IE-specific risk scores have been developed recently, but there is a paucity of external validation studies. We aimed to pool the performance of current risk models applied to IE surgery. Methods Ovid Medline, Ovid Embase and Cochrane Library were comprehensively searched following PRISMA guidelines for eligible studies. Standard meta-analysis techniques using random effects models were used to pool the discriminative and calibration performance of risk scores for predicting operative mortality after IE surgery. Results Amongst 620 studies and 50 full-text articles screened, 17 studies reporting 12 risk scores and totaling 6337 patients were included. Amongst traditional risk scores, EuroSCORE I, EuroSCORE II, and STS IE score had pooled areas under curve (95%CI) of 0.727 (0.700.754), 0.753 (0.731-0.775), and 0.695 (0.645-0.746) (Table1). However, EuroSCORE II significantly over-estimated operative mortality while EuroSCORE I had good calibration with pooled Peto’s odds ratio (95%CI) of 2.47 (1.22-5.01) and 1.00 (0.74-1.36) respectively. Amongst IE-specific scores, areas under curve (95%CI) was highest for the ANCLA score 0.838 (0.803-0.873) and lowest for the COSTA score 0.641 (0.573-0.710). Conclusion Most contemporary risk score had moderate discriminative ability for operative mortality after IE surgery, with the IE-specific ANCLA score performing the best. However, there is room for improving the performance of current risk models, along with need for further external validation studies and calibration assessment, especially for IE-specific scores.

Left ventricular strain-volume loops in bicuspid aortic valve: new insights in hemodynamics and prognostic value

Abstract Background Bicuspid aortic valve (BAV) is a common congenital cardiac disease with a high risk of adverse outcomes. By combining left ventricular (LV) global longitudinal strain (GLS) with LV volume during the cardiac cycle, LV strain-volume loops (SV-loops) can be generated. This may be a valuable biomarker in early detection of LV deterioration. The aim of this study is to describe SV-loop characteristics in BAV patients and investigate its prognostic value. Methods BAV patients were compared with healthy controls, matched for age and sex on a group level. Apical 2, 3 and 4 chamber views were used to measure LV GLS and volume to construct SV-loops. The parameters measured from these SV-loops are depicted in Figure 1A. Associations with the composite endpoint of all-cause mortality, heart failure and supraventricular and ventricular arrhythmias were assessed by univariable Cox regression. Results 113 BAV patients were included (median age 32 years, 40% female). The median aortic jet velocity was 2.3 m/s [IQR 1.6-3.3] and 21 patients (19%) had moderate aortic regurgitation. A clear rightward shift in average SV-loops was seen between BAV patients and healthy controls (figure 1B). Sslope was significantly lower in BAV patients (0.21%/mL, [IQR 0.17-0.28] vs. 0.27%/mL [0.24-0.34], p<0.001), as was ESslope (0.19%/mL [0.12-0.25] vs. 0.29%/mL [0.21-0.43], p<0.001). Moreover, greater uncoupling was seen in BAV patients, both early (0.48±1.29 vs. 0.05±1.21, p=0.018) and late diastolic (0.66±1.02 vs -0.07±1.07, p<0.001). During a median follow-up period of 9.9 years [9.3-10.4], 17 patients experienced a primary endpoint. Echocardiographic parameters associated with the primary endpoint were early diastolic uncoupling (HR 1.82, p=0.009), E/e’ ratio (HR 1.29, p<0.001), ESslope (HR 0.55, p=0.03) and LV end-systolic volume (HR 1.05, p=0.03). Conclusion Significant differences in SV-loop characteristics were observed between BAV patients and healthy controls, suggesting its capability to provide new insights in cardiac hemodynamics and detect LV remodelling at an early stage. Moreover, SV-loops can be promising new prognostic markers.

Association between Serum Lactate and Morbidity and Mortality in Neonates: A Systematic Review and Meta-Analysis.

Lactate is a marker of hypoperfusion in critically ill patients. Whether lactate is useful for identifying and stratifying neonates with a higher risk of adverse outcomes remains unknown. This study aimed to investigate the association between lactate and morbidity and mortality in neonates. A meta-analysis was performed to determine the association between blood lactate levels and outcomes in neonates. Ovid MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials.gov were searched from inception to 1 May 2021. A total of 49 observational studies and 14 data accuracy test studies were included. The risk of bias was assessed using the Newcastle-Ottawa Scale for observational studies and the QUADAS-2 tool for data accuracy test studies. The primary outcome was mortality, while the secondary outcomes included acute kidney injury, necessity for renal replacement therapy, neurological outcomes, respiratory morbidities, hemodynamic instability, and retinopathy of prematurity. Of the 3184 articles screened, 63 studies fulfilled all eligibility criteria, comprising 46,069 neonates. Higher lactate levels are associated with mortality (standard mean difference, -1.09 [95% CI, -1.46 to -0.73]). Using the estimated sensitivity (0.769) and specificity (0.791) and assuming a prevalence of 15% for adverse outcomes (median of prevalence among studies) in a hypothetical cohort of 10,000 neonates, assessing the lactate level alone would miss 346 (3.46%) cases (false negative) and wrongly diagnose 1776 (17.76%) cases (false positive). Higher lactate levels are associated with a greater risk of mortality and morbidities in neonates. However, our results do not support the use of lactate as a screening test to identify adverse outcomes in newborns. Research efforts should focus on analyzing serial lactate measurements, rather than a single measurement.

Abstract 12446: Trajectories of Frailty and Cardiovascular Outcomes Among Medicare Beneficiaries, 2003-2015

Background: Frailty is associated with adverse cardiovascular outcomes independent of age and comorbidities, yet the independent role of frailty progression on health outcomes remains uncertain. Methods: In Medicare Fee-for-Service beneficiaries ≥ 65 years with continuous enrollment from 2003-2015, we calculated frailty progression or regression, using a continuous, validated Fried phenotype-based frailty index in years 1-5. We used linear mixed effects models and Cox proportional hazards models, adjusting for baseline frailty, to evaluate the influence of frailty trajectory on the risk of adverse health outcomes (death, HF, MI, ischemic stroke, MACE, and days at home [DAH] within the calendar year). Results: Among 26,414,887 individuals (mean age 75.4 ± 7.0 years, 57% female, 13% non-white race), 20.4% had frailty progression and 13.6% had frailty regression. Compared to frailty regressors, progressors had a greater risk of mortality (HR 1.59, 95% CI 1.58-1.59) and all cardiovascular outcomes. With increasing quartile of frailty progression and adjusting for baseline frailty, there was a graded risk in mortality (quartile 4 vs. 1, HR 2.21, 95% CI 2.21-2.23, p < 0.001) and all adverse cardiovascular outcomes (Figure). Compared to those in the lowest frailty progression quartile, those in the highest quartile had significantly fewer DAH (270.4 ± 112.3 vs. 308.6 ± 93.0, RR 0.88, 95% CI 0.87-0.88, p < 0.001). Conclusions: In this large, nationwide sample of older Medicare beneficiaries, the degree of frailty progression, independent of baseline frailty, was associated with increased risk of all-cause mortality, HF, MI, ischemic stroke, and MACE, and fewer DAH. Frailty progression therefore identifies patients at high risk for adverse outcomes and increased health services utilization.

Abstract 11954: Predictors of Adverse Outcome in STEMI Patients Post-PCI With Cardiogenic Shock Requiring Intra-Aortic Balloon Pump Support

Introduction: Cardiogenic shock is a serious complication of ST-segment elevation myocardial infarction (STEMI), however clinical and demographic factors may further impact outcomes. This study investigated how age, gender, income, comorbidities, and arrhythmias affect mortality of STEMI patients receiving intra-aortic balloon pumps (IABP) for management of cardiogenic shock. Methods: This retrospective study used the National Inpatient Sample (NIS) database from 2016 to 2020. We identified STEMI admissions as the principal diagnosis and cardiogenic shock as the secondary diagnosis. Patients who received IABP support were included using the ICD-10 Procedure Coding System (PCS) code 5A02210. Logistic linear regression was used to analyze the data while adjusting for confounding variables such as age, sex, and comorbidities. Results: Of the 24,915 admissions with STEMI requiring IABP post PCI, the average age was 65, 29.5% were female, 28.8% died and 51.7% patients had congestive heart failure. The highest mortality rate was associated with liver disease, followed by left bundle branch block, age over 65, ventricular fibrillation, renal failure, female gender, peripheral vascular disease (PVD), and ventricular tachycardia (table 1). Income in the bottom 25 th percentile also had increased mortality. Conclusion: This study identified several predictors of adverse outcomes in post-PCI STEMI patients with cardiogenic shock requiring IABP support, including ventricular fibrillation, ventricular tachycardia, left bundle branch block, peripheral vascular disease, renal failure, liver disease, age 65 or older, female, and low income. These findings may aid in the management of STEMI patients with cardiogenic shock by allowing healthcare providers to identify patients at high risk for adverse outcomes and tailor their treatment accordingly.

Abstract 13795: Reduced Fetuin-A Levels Are Associated With Exercise Intolerance in Patients With Heart Failure and Predict the Risk of Adverse Outcomes

Background: Impaired exercise tolerance is a feature of heart failure (HF) and predicts adverse outcomes in patients with HF. Hepatokines are proteins synthesized and secreted by the liver, which regulate systemic metabolisms of peripheral tissues. However, the clinical impact of hepatokines on exercise capacity has not been well understood. Aims: Our objective was to investigate the relevance of a hepatokine, Fetuin-A, in relation to exercise capacity in HF. Methods and Results: We conducted a prospective study involving 120 consecutive hospitalized patients (mean 57.3 years old, 75.0% male) with HF who underwent cardiopulmonary exercise testing. The serum concentration of Fetuin-A was measured by an enzyme-linked immunosorbent assay. Patients with impaired exercise tolerance (peak oxygen uptake (VO 2 ) < 14.0 mL/kg/m) exhibited lower Fetuin-A levels than those without ( Figure A ). Correlation analysis revealed that Fetuin-A was positively correlated with peak VO 2 and negatively correlated with minute ventilation to carbon dioxide production ratio and its slope. We then followed up patients and found 12 composites of cardiac events that included 5 cardiac death and 7 worsening HF. Based on classification and regression tree to determine the cut-off of Fetuin-A, Kaplan-Meier analysis revealed that patients with lower Fetuin-A levels (< 22.2 ng/mL) and impaired exercise tolerance had the highest risk of cardiac events ( Figure B ). In a multivariable Cox proportional hazard model, the presence of both lower Fetuin-A and exercise intolerance was independently associated with an increased risk of cardiac events (hazard ratio, 18.8; P = 0.009). Conclusions: Reduced Fetuin-A levels were associated with exercise intolerance in patients with HF, and those with decreased levels of both Fetuin-A and peak VO 2 were at the highest risk of adverse outcomes.

Abstract 12044: Sex-Related Differences in Long-Term Outcomes Across the Spectrum of Left Ventricular Ejection Fraction in Acute Decompensated Heart Failure Patients

Background: An important knowledge gap remains on sex-related differences in heart failure (HF) management. Recently, it has been recognized that patients, particularly women, with supra-normal left ventricular ejection fraction (snLVEF) are at high risk of adverse outcomes. Aims: We sought to evaluate the sex related differences of long-term outcomes across the spectrum of LVEF in acute decompensated HF (ADHF) patients. Methods: We analyzed 3943 ADHF patients (age 77 years; 59.8% male) who were enrolled in WET-HF multicenter registry in Japan from 2006 to 2017. The association of long-term outcomes across the spectrum of LVEF were compared between men and women. Results: In both HF with reduced EF (HFrEF; LVEF < 50%) and preserved EF (HFpEF), female patients were older and had lower body mass index, lower prevalence of ischemic etiology, and smaller LV chamber size. In HFrEF, implementation of guideline-directed medical therapy such as the combination of renin-angiotensin-system inhibitor (RASi), β-blocker and mineralocorticoid receptor antagonist (MRA) was significantly lower in women at discharge, even after adjustment for covariates (RASi + β-blocker : odds ratio [OR], 0.80, p=0.049; RASi + β-blocker + MRA: OR, 0.73, p=0.016). Female patients showed higher incidence of the primary endpoint, defined as the composite of cardiac death and ADHF readmission during 1,000 days after discharge ( p = 0.009, log-rank test). However, female sex did not remain significant after adjustment for covariates. Restricted cubic spline analysis demonstrated a U-shaped relationship with a nadir at LVEF 60% between LVEF and the hazard ratio of the primary endpoint in women, but this relationship was not observed in men ( p for interaction = 0.048, Figure A, B ). This trend was more evident after excluding patients with valvular heart disease ( p for interaction = 0.014, Figure C, D ). Conclusions: In women, not only low LVEF but also snLVEF were associated with worse long-term outcomes.

Norms for Usual and Fast Walking Speed in Adults 45-69 Years Old From the French General Population: Constances Study

ObjectivesWalking speed (WS) represents an objective measure of motor function and health. We aimed to develop usual (UWS) and fast WS (FWS) norms for the general population using a regression-based approach, while considering age, sex, height, and education. DesignCross-sectional analysis of a population-based study. Setting and ParticipantsFrench Constances study (45-69 years). MethodsUWS/FWS were measured over 3 m (dynamic start) using photoelectric cells. We addressed selection effects (related to survey sampling and nonresponse) and missing data using a combination of inverse probability weighting (IPW) and multiple imputation (MI). Norms by sex, age, height, and education (<tertiary/≥tertiary) were estimated using a 3-level linear mixed effects model (random effects on center and year) allowing for nonlinear relations that were adjusted for age, sex, height, education, and significant 2-way interactions. ResultsAnalyses are based on 44,772 participants (51.2% women) with a mean age of 56.8 years (SE = 0.2) for women and 57.3 years (SE = 0.2) for men, and a mean height of 161.4 cm (SE = 0.1) for women and 174.2 cm (SE = 0.1) for men after IPW/MI. WS estimates decreased after IPW/MI. The mean UWS was 116.9 cm/s (SE = 0.8) in women and 120.7 cm/s (SE = 0.8) in men, and the mean FWS was 168.7 cm/s (SE = 1.0) in women and 182.8 cm/s (SE = 1.2) in men. In the multiadjusted model, UWS/FWS decreased with age and increased with height and education. Men had faster FWS than women; they had slightly slower UWS than women in the low-education group, but there were no sex differences in the high-education group. Conclusions and ImplicationsWe developed UWS/FWS norms by age, sex, height, and education for the French general population (45-69 years) that are available through a web app (https://cesp-proxy2.vjf.inserm.fr/NORMES-VM-EN/). These norms can be used to identify in midlife persons with lower motor performances than the general population, given their age, sex, height, and education, who are at higher risk of adverse outcomes.