Risk Of Hospitalization Research Articles

Uptitration of Sacubitril/Valsartan and Outcomes in Patients With Heart Failure - Insight From the REVIEW-HF Registry.

Guideline-directed medical therapy has become an important component of heart failure (HF) therapy, with sacubitril/valsartan as one of the recommended drugs; however, the real-world prognostic implications of sacubitril/valsartan uptitration are unclear. Patients with HF newly initiated on sacubitril/valsartan were registered in a retrospective multicenter study (REVIEW-HF). In all, 995 patients were divided into 3 groups according to the maximum dose achieved: high dose, sacubitril/valsartan 400 mg; intermediate dose, sacubitril/valsartan 200-<400 mg; and low dose, sacubitril/valsartan <200 mg. A total of 397 (39.9%) patients received high-dose sacubitril/valsartan; they had a significantly lower risk of mortality or HF hospitalization than patients in the low-dose (hazard ratio [HR] 0.39; 95% confidence interval [CI] 0.29-0.53; P<0.001) and intermediate-dose (HR 0.64; 95% CI 0.45-0.94; P=0.03) groups. In the multivariable Cox regression model, higher systolic blood pressure and maintained geriatric nutritional risk index were significantly associated with a higher incidence of achieving a high dose of sacubitril/valsartan. Patients who did not receive high-dose sacubitril/valsartan experienced more hypotension during the follow-up period, whereas hyperkalemia, severe renal events, and angioedema did not differ across the achieved dose classifications. Patients who achieved sacubitril/valsartan uptitration had a better prognosis than those who did not. Before sacubitril/valsartan uptitration, patients need to monitor blood pressure closely to prevent worsening events.

Post-COVID syndrome and type 2 diabetes mellitus in Kazakhstan: clinical manifestations and vaccine efficacy.

In this article, we report the results of a survey investigating post-coronavirus disease 2019 (COVID-19) syndrome in patients with type 2 diabetes mellitus and the impacts of vaccination on long-term manifestations. From February 2022 to April 2023, a survey of patients with type 2 diabetes and people without diabetes who were treated for a coronavirus infection was conducted in Kazakhstan. Participants were invited via social media to voluntarily participate in this study. A total of 417 surveys were included in this study, comprising 212 patients with type 2 diabetes and 205 without diabetes. We compared persistent complaints after recovery in patients with and without diabetes mellitus (DM), as well as vaccination status. The results of this study on self-reported symptoms of prolonged COVID show that more than half of those infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Kazakhstan have at least one persistent symptom after recovery. Based on the list of prolonged COVID-19 symptoms reported by patients with type 2 DM (T2DM), exertional dyspnoea, fatigue, respiratory discomfort, headaches, and sleep disturbances are among the most common ongoing conditions, and in many cases last more than 3 months after COVID-19. Patients with T2DM experience more severe and prolonged symptoms than those without diabetes. Additionally, vaccination lowers COVID-19 hospitalization risk and decreases the need for adjusting hypoglycemic therapy, such as insulin treatment, after recovering from SARS-CoV-2 infection.

The Impact of Comorbidity and Age on the Risk of Hospitalization and Mortality in Patients with Previous COVID-19 Infection-Based on Nationwide Data.

Objectives: The influence of comorbidity on long-term hospitalization and mortality after COVID-19 in adults (40-59 years) and older adults (≥60 years) is yet to be explored. Methods: This is a Danish population-based cohort study of patients with a first-time positive PCR test for COVID-19 from 1 March 2020, to 28 February 2022 (N = 1,034,103). Exposed cohorts were patients with 1) a Charlson Comorbidity Index (CCI) score of 1-2 and 2) a CCI score ≥3, who were compared to patients without comorbidity (CCI of zero) within the groups of adults (67.9%) and older adults (32.1%) for the risk of hospitalization and mortality. Next, within the age groups, each disease category of the CCI was considered as an exposed cohort and compared to patients who did not have the specific disease of interest. Adjusted hazard ratios (HR) for hospitalization and mortality were estimated by Cox regression models adjusted for confounders. Results: The highest HRs were in adult patients with a CCI score of ≥3. The adjusted HR was 4.54 (95%CI: 4.38-4.70) for hospitalization, and among older adults it was 3.05 (95%CI: 2.99-3.11). The adjusted HR for mortality among adults with a CCI score ≥3 was 21.04 (95%CI: 18.86-23.47), and the adjusted HR for mortality among older adults was 4.61 (95%CI: 4.44-4.78). The underlying disease influenced the risk estimates among adults and older adults, and "dementia" had the highest impact on mortality. Conclusion: A CCI score of 1 or above increases the risk of hospitalization and mortality up to 2 years after a positive PCR test of COVID-19 for adults and older adults. Further, the type of underlying disease in older adults highly influences the risk of hospitalization and mortality.

Impact of sex-specific thresholds for low flow in assessment of prognosis in concordantly and discordantly graded aortic valve stenosis.

Sex-specific low flow was recently defined as stroke volume index (SVi) ≤40 ml/m² in men and ≤32 ml/m² in women. We tested the prognostic association of these cut-offs in patients with aortic stenosis (AS) with concordantly and discordantly graded AS (CGASEL and DGASEL) based on pressure recovery adjusted aortic valve area (energy loss, EL). Data from 1351 patients with asymptomatic AS, peak jet velocity <4m/s and preserved left ventricular ejection fraction enrolled in the Simvastatin and Ezetimibe in AS study was used. DGASEL was defined as EL <1.0 cm² with mean aortic gradient <40 mmHg, and CGASEL as EL ≥1.0 cm² with mean aortic gradient <40mmHg. Patients were further grouped into normal and low flow. Outcome was combined all-cause death and hospitalization for heart failure. CGASEL with normal/low flow was present in 915/253 patients, and DGASEL with normal/low flow in 57/126 patients. During median 4.3 years follow-up, event-free survival was lower in patients with DGASEL irrespective of flow compared to CGASEL with normal flow (p<0.05). In Cox regression analysis, DGASEL with normal or low flow were both associated with increased risk of all-cause death and hospitalization for heart failure after adjustment for age, sex, heart rate, randomized study treatment, hypertension, aortic valve replacement and aortic valve calcification (p<0.05). No survival difference was found between patients with normal vs. low flow within groups of DGASEL or CGASEL. Identification of low flow by the proposed sex-specific thresholds of SVi needs more prognostic validation before application in clinical practice.

Association of Benzodiazepine Prescription With Short-Term Prognosis in Elderly Patients Attended in Emergency Department: Results From the EDEN PROJECT.

Benzodiazepine prescription is a growing phenomenon among the elderly population. However, information related to the frequency of these drugs among the elderly population attending in emergency departments (ED) and its impact over prognosis is scarce. The aim of this study is to assess the prevalence of benzodiazepine prescription and to analyze its association with short-term prognosis in elderly patients attended in ED. A retrospective analysis of the EDEN (Emergency Department Elderly in Need) cohort was conducted. This registry included all elderly patients attending in 52 Spanish EDs for any condition, between April 1st and 7th in 2019. Socio-demographic data, comorbidities, and medication were recorded by consulting the patient's electronic health records. The assessed outcomes consisted on new ED visit, hospitalization, and mortality at 30 days after the first ED visit, associated with the use of benzodiazepines at baseline in comparison with no prescription of benzodiazepines. Crude and adjusted logistic regression analyses including patient's comorbidities were performed. Two sensitivity analyses were performed considering concomitant prescription of other central nervous system depressants as well as direct discharge from the ED. 25 557 patients were evaluated (mean age 78 [IQR: 71-84]). 7865 (30.8%) patients were taken benzodiazepines at admission. After adjustment for comorbidities and other central nervous system drugs, benzodiazepine prescription was associated with ED revisit [OR: 1.10 (95%CI: 1.03-1.18)]. Similar results were found in the sensitivity analysis, eliminating patients with central nervous depressors [OR: 1.11 (1.03-1.25)] and patients discharged to home [OR: 1.13 (1.04-1.23)]. No association was found between the use of these drugs and new hospitalizations [OR: 0.90 (0.77-1.05)] or mortality 30 days after discharge [OR: 1.01 (0.88-1.18)]. The results held for all three outcomes in the sensitivity analyses. The use of benzodiazepines is a frequent phenomenon among the elderly population attended in the ED, being associated with an increased risk of new visits to the emergency room, but not with an increased risk of 30-day hospitalization or mortality.

Vericiguat Global Study in Participants with Chronic Heart Failure: Design of the VICTOR trial.

In the VICTORIA (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction) trial, the soluble guanylate cyclase stimulator vericiguat reduced the risk of hospitalization for heart failure (HHF) or cardiovascular death in patients with heart failure (HF) and reduced ejection fraction (HFrEF) with recent worsening HF. The effect of vericiguat in patients with HFrEF without recent worsening HF remains unknown. The VICTOR (Vericiguat Global Study in Participants with Chronic Heart Failure) trial was designed to assess the efficacy and safety of vericiguat in patients with ejection fraction ≤40% without recent worsening HF on a background of current foundational HFrEF therapy. The primary endpoint for VICTOR is time to first event for the composite of HHF or cardiovascular death. The trial will also assess the effect of vericiguat on time to cardiovascular death, time to HHF, total HHF, and all-cause death. As an event-driven trial, at least 1080 primary events are expected, but follow-up will continue until the targeted number of at least 590 cardiovascular deaths has been reached. Approximately 6000 participants will be randomized to vericiguat or placebo. VICTOR is the first large event-driven HFrEF trial performed in the contemporary era of quadruple foundational guideline-directed medical therapy, in a compensated ambulatory HF population. VICTOR will add important information to the evidence of the effects of vericiguat across the spectrum of patients with HFrEF.

Sodium-glucose cotransporter-2 inhibitors in acute myocardial infarction: a systematic review and meta-analysis of randomized controlled trials.

We aimed to assess the efficacy and safety of sodium-glucose cotransporter-2 inhibitors (SGLT2i) versus placebo, initiated within the hospitalization period, in addition to habitual treatment, for treating adult patients with confirmed acute myocardial infarction (AMI). We also conducted subgroup analysis by diabetes mellitus (DM) status and type of AMI. We systematically searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCTs). The primary outcome was hospitalization for heart failure (HF). The secondary outcomes were all-cause death, cardiovascular death, and serious adverse events (AEs). We pooled risk ratios (RR) with a 95% confidence interval (CI) for binary outcomes. The between-study variance was assessed using tau2 statistics. We included five RCTs, encompassing 11,211 patients. SGLT2i significantly reduced the risk of hospitalization for HF compared to placebo (RR 0.73; 95% CI [0.61, 0.88]). However, the risk of all-cause death (RR 1.05; 95% CI [0.78, 1.41]) and cardiovascular death (RR 1.04; 95% CI [0.84, 1.29]) was similar between the groups, as well as the risk of serious AEs (RR 1.01; 95% CI [0.90, 1.14]). In the subgroup analysis by DM status and type of AMI, there were no significant subgroup differences for the outcomes of hospitalization for HF and all-cause death. In patients with AMI, treatment with SGLT2i is safe and significantly reduces the risk of hospitalization for HF, but it has no impact on all-cause death and cardiovascular death compared to placebo.

Risk and causes of hospital admission in patients with atrial fibrillation on treatment with oral anticoagulants

Abstract Background Atrial fibrillation (AF) is associated with an increased risk of hospitalisation, although the main reasons for hospital admission and the role of antiarrhythmic drugs are not clarified. Objective The aim of our study was to assess the incidence rate and the factors associated with all-cause, cardiovascular and AF-related causes of hospitalisation in patients suffering from AF. Methods This is a prospective single-centre ongoing study (ATHERO-AF cohort) which included 2782 patients affected by non-valvular AF on oral anticoagulants. The primary endpoints were all-cause, cardiovascular and AF-related hospitalisation. Cardiac hospitalizations were defined as (non-AF) arrhythmias, acute coronary syndromes, heart failure (HF), systemic embolism, hypertensive urgency, vascular/cardiac surgery. The AF-related hospitalisation was defined as a recurrence of AF in paroxysmal pattern or as a high-rate symptomatic AF episode in persistent/permanent patterns. Multivariable Cox proportional hazards regression analysis was used to calculate the hazard ratio (HR) with 95% Confidence interval (95%CI) for each factor in relation to risk of hospitalisation. Results Overall, 43.5% of patients were women with a mean age of 74.6±9.1year. Patients were followed for a mean of 31±26.8 months. We registered 1205 (12.1%/year) hospitalisations for any reason, 533 (5.7%/year) for cardiovascular causes and 180 (2.0%/year) were AF-related hospitalisations (Central illustration). Among the anti-arrhythmic drug use, we highlighted that flecainide and propafenone were associated with AF-related hospitalisations in paroxysmal and in persistent/permanent patterns (HR 1.861, 95%CI 1.116-3.101 and HR 1.947, 95%CI 1.069-3.548, respectively). Amiodarone (HR 3.012, 95%CI 1.835-4.943) and verapamil or diltiazem (HR 2.067, 95%CI 1.117-3.825) were associated with an increased risk of AF-related hospitalisations in persistent/permanent AF pattern. Furthermore, cancer was associated (HR 1.802, 95%CI 1.057-3.070) with increased risk of hospitalisation due to AF-related causes. Conversely, beta-blockers and digoxin were not associated with increased risk of hospital admission. Conclusions Hospitalisations of patients with AF are frequent for both cardiovascular and non-cardiovascular causes. Among the AF-related ones, the use of antiarrhythmic drugs emerged as associated with increased risk of hospitalisations, hypothesizing their poor effect in preventing AF episodes. For these reasons, we suggest carefully considering their use, reserving them for symptomatic patients with frequent AF recurrences.Central Illustration

Permanent pacemaker implantation is associated with an increased risk of heart failure hospitalization in transcatheter aortic valve implantation patients with reduced systolic function

Abstract Background The impact of permanent pacemaker implantation (PPI) on outcome of patients following transcatheter aortic valve implantation (TAVI) is not fully understood. Purpose This study aimed to assess the impact of PPI on risk of two-year mortality and hospitalization due to heart failure (HF) in TAVI patients. Methods A total of 1275 consecutive patients who underwent TAVI at our hospital between 2009 and 2021 were enrolled in this study (mean age 81.4±5.6 years, 51.8% male). The primary endpoint was defined as two-year all-cause death after TAVI. The second endpoints included cardiovascular (CV) death and HF related hospitalization after TAVI. Results Among the 1275 patients following TAVI, 297 (23.3%) patients received PPI, with 134 receiving PPI before TAVI and 163 receiving PPI after TAVI. The patients were categorized into two groups: no PPI group (n=978) and PPI group (n=297). Compared to patients without PPI, patients who received PPI were more likely to be male (60.9% vs. 49.1%, P&amp;lt;0.001), higher prevalence of atrial fibrillation (51.2% vs. 43.3%, P=0.016), coronary artery disease (61.6% vs. 53.8%, P=0.017), use aldosterone receptor antagonists (MRAs, 25.3% vs. 15.2%, P&amp;lt;0.001), and lower left ventricular ejection fraction (LVEF, 54.9±13.1% vs. 57.5±11.4%, P&amp;lt;0.001). There were no significant differences in all-cause mortality (16.6% vs. 18.5%), CV mortality (11.3% vs. 13.5%), as well as HF hospitalization rate (18.5% vs, 21.2%) between the two groups (P&amp;gt;0.05). In this cohort, 1012 (79.4%) TAVI patients had a preserved LVEF (≥50%), 122 (9.6%) had a mildly reduced LVEF (41-49%), and 141 (11.1%) had reduced LVEF (≤40%). Their primary and secondary outcomes were similar among LVEF subgroups (all P&amp;gt;0.05). In the subgroup of reduced LVEF, the HF related hospitalization rate after TAVI was significantly higher in TAVI patients with PPI compared to those without PPI (30.6% vs. 13.0%, P=0.003). Multivariable Cox regression models demonstrated a 3-fold increased risk of HF related hospitalization in TAVI patients with PPI in comparison to those without PPI in the subgroup of LVEF≤40% (HR 3.057, 95% CI 1.311-7.130, P=0.010) after adjusting for age, sex, TAVI approach, atrial fibrillation, coronary artery disease, and the use of MRAs. Conclusion All-cause mortality and CV mortality are similar between TAVI patients with and without PPI. However, in the subset of TAVI patients with reduced LVEF (≤40%), PPI is associated with an increased risk of HF hospitalization. Efforts are thus needed to reduce the risk of HF hospitalization in these patients.

Temporal trends in mortality and hospitalisation risk in patients with heart failure according to frailty status

Abstract Background Heart failure (HF) and frailty often coexist, and patients with both conditions have a higher risk of mortality and hospitalisation compared with those who are not frail. Over the past two decades, advances in medication targeting HF have been introduced, prolonging the life of patients with HF, but also resulting in increased comorbidity accumulation and susceptibility to frailty. It remains unknown how the interplay between HF and frailty at HF onset impacts patient prognosis and how this has changed over time. Purpose We investigated the temporal trends in the risk of all-cause mortality and HF hospitalisation in patients with HF from 1999 to 2017 according to their frailty status. Methods From Danish nationwide registers, we included patients with new-onset HF. Patients were categorised into four groups according to the year of HF onset: 1999-2002, 2003-2007, 2008-2012, and 2013-2017. The Hospital Frailty Risk Score was used to classify patients into frailty severity categories: 1) non-frail, 2) moderately frail, and 3) severely frail. The primary outcome was the 5-year cumulative incidence of all-cause mortality, assessed using the Kaplan-Meier estimator. The secondary outcome was the 5-year risk of HF hospitalisation, assessed using the Aalen-Johansen estimator, accounting for the competing risk of death. Moreover, a sensitivity analysis was conducted using a multivariable Cox proportional hazard model, investigating the interaction between year group and frailty status for all-cause mortality, comparing frail patients with non-frail patients. Results Among 131,235 patients with HF (median age 74 years; 39.7% female), 102,635 (78%) were categorised as non-frail, 26,054 (20%) as moderately frail, and 2609 (2%) as severely frail. The proportion of moderately frail patients increased the most, from 13% in 1999 to 25% in 2017. From 1999-2002 to 2003-2017, the 5-year cumulative incidence of all-cause mortality declined from 56.4% (95% CI, 55.8-57.0%) to 33.3% (32.6-34.1%), 79.8% (78.5-81.0%) to 58.6% (57.2-60.1%), and 90.8% (85.6-96.0%) to 79.8% (76.4-83.2%) in the non-frail, moderately frail, and severely frail patient group, respectively (Fig 1). The largest relative improvement was observed in the non-frail patient group. The 5-year cumulative incidence of HF hospitalisation remained fairly constant across the frailty groups (Fig 2). Conclusions From 1999 to 2017, we observed an increase in moderately and severely frail patients. Overall, the mortality risk decreased across all frailty groups. These findings underscore the importance of implementing guidelines directed at frail patients with HF.5-year risk of all-cause mortality5-year risk of HF hospitalisation

The association of NT-proBNP levels in atrial fibrillation patients and 3-year risk of heart hospitalization and death

Abstract Background NT-proBNP-levels are often elevated in patients with atrial fibrillation (AF), but their clinical use and interpretation for predicting subsequent cardiovascular events has not been explored in an all-comers setting. Aim To determine whether NT-proBNP levels are associated with the risk of subsequent heart failure (CHF) and/or death in patients with AF and its relation to prior CHF diagnosis Method All patients with new-onset AF (defined by ICD-code I48) who had an NT-proBNP-level within +/- 14 days of the date of the AF date measured in a regional laboratory repository between 2000-2021 were included in the analysis cohort. Patients were categorized into NT-proBNP level (pg/mL) &amp;lt;1000, 1000-1999, ≥2000. If several NT-proBNP-levels were measured, the maximal value was used. The association between NT-proBNP level and the outcome CHF hospitalization and/or death within 3 years of diagnosis was assessed in Cox regression analyses adjusted for baseline characteristic and medications. Since there was an interaction (p&amp;lt;0.001) between Nt-proBNP-level and prior/new-onset CHF at time of AF diagnosis and no known CHF, two separate analyses were performed in patients with or new-onset CHF and those without prior CHF. Results There were 10559 patients with AF and no CHF, and 11 257 with AF and CHF. There were 14% of patients with new-onset CHF at time of new-onset AF diagnosis. These were grouped together with patients with known CHF. Patients with no prior CHF were younger (76 years (95% CI 68-83) vs 80 (72-87), p&amp;lt;0.001), and healthier with less often diabetes (18.4% vs 24.5%, p&amp;lt;0.001), prior myocardial infarction (12.0% vs 24.3%), a lower CHA2DS2-VASc score (3.0 vs 5.0, p&amp;lt;0.001) and a lower median NT-proBNP level (1650 pg/mL (95% CI 702-3549) vs 4240 pg/mL (2160-8860), p&amp;lt;0.001). Among patients with AF and no prior CHF, the incidence rate in the lowest NT-proBNP level was low, but increased with higher levels (Table). Adjusting for covariates and medications, the risk of both CHF hospitalization and CHF/death compared to the reference category NTproBNP&amp;lt; 1000 pg/mL was nearly 2 and 3 times higher among those who with initial NT-proBNP level 1000-1999 and ≥ 2000. Among patients with AF and known CHF, the incidence rate of CHF hospitalization or CHF hospitalization/death at the same NT-proBNP-strata was several times higher compared to patients without known CHF. Adjusting for covariates, the risk increased for CHF hospitalization or CHF/hospitalization similarly for each strata as for patients without known CHF. AF patients without known HF but with the highest elevation of NTproBNP-level had a risk of subsequent hospitalization of heart failure which was higher than those with known heart failure and lowest NTproBNP-level. Conclusion A higher NTproBNP-level in patients with AF identifies patients at higher risk of CHF hospitalization and/or death in both patients with no and prior CHF.Table

Machine Learning techniques for predicting inpatient probability and LOS from EU Injury Database

Abstract Background Unlike statistical inference Machine Learning (ML) makes repeatable predictions without prior assumptions about the underlying relationships among variables. The Full Data Set (FDS) of the EU-IDB (European Injury DataBase) consent to explore risk of hospitalization due to injuries using many predictors. The Length Of Stay of patients in hospital (LOS) is a relevant proxy of complexity of treatment and resources consumption. Methods The IDB-FDS provides more than 3.800.000 ED records, in years 2008-19 for 19 Countries. LASSO (Least Absolute Shrinkage and Selection Operator) cross-validated linearized regression technique (linear for LOS) was used for variable selection and parameter regularization. Inpatients are those admitted or transferred to hospital. Days of hospitalization were used for LOS. A cross-validated Generalized Linear Model was performed on 5 folds randomly sampled assigning 80% of records to training and 20% to testing samples. Results The strongest predictors of hospital admission risk, selected by the model were in order of importance: EUROCOST-39 diagnoses categories, Age Group, Intent, Mechanism Of Injury, Activity When Injured, Transport Injury Event, Sex Of Patient, Place Of Occurrence. EUROCOST-39 represents 61,9% of explained variability and age group 19,4%. The strongest predictors of LOS were substantially the same: EUROCOST-39 86,2% of explained variability and age group 8,6%. Conclusions The main part of variability in the ML model is explained by diagnoses reclassified according to a disability standardization method. For instance, in the maximum training sample risk of hospitalization ranges from odd 0,76% for hand/fingers sprain up to 154,02% for brain concussion. In the median sample LOS ranges from 0,45 days for strain of hand/fingers up to 11,65 for multi-trauma. A combination of more disabling injury, older age and mechanism of injury (i.e. threat to breathing) increases enormously the risk of hospitalization and LOS. Key messages • Machine Learning techniques applied on EU-IDB can provide identification of relevant risk factors of hospital admission from injuries for targeting preventive measures and organizing health care. • Artificial Intelligence consents to analyse big amount of data as dimension or analytical detail of information for identifying patterns and predictors of specific indicators for injuries or diseases.

Neighbourhood immigrant density and COVID-19 infection and hospitalization among healthcare workers

Abstract Background Studies have shown inequalities in COVID-19 infection among healthcare workers (HCWs), with occupational exposure failing to fully explain the inequalities. Little is known about the role of other social determinants of health, such as neighborhood immigrant density. We examined if living in immigrant-dominated neighborhoods was associated with increased risk of COVID-19 infection and hospitalization among HCWs in Sweden, and if so, whether such exposure amplified the risk of COVID-19 among immigrant HCWs. Addressing this question would contribute to a better understanding of factors driving COVID-19 disparities among HCWs. Methods Data were from HCWs aged 20 to 62 years (N = 86187) resident in one of 14 Swedish municipalities (three of which are Sweden’s largest metropolitan cities) on 1 January 2020. Residential neighborhoods were categorised into Swedish-dominated, mixed, and immigrant-dominated. The study outcomes were the first occurrence of COVID-19 infection and hospitalization registered until 30 September 2022. Multilevel mixed-effects survival regression was used for the association analyses, with control for confounders (age, sex, income, comorbidities etc). Results After adjusting for confounders, living in immigrant-dominated neighborhoods was only associated with an increased risk of COVID-19 infection in the first pandemic wave (HR 1.17, 95%CI 1.07 - 1.29), but living in these areas was associated with an elevated risk of COVID-19 hospitalization throughout the entire period. Immigrant HCWs, regardless of where they lived, had around 2-fold higher risk of being hospitalised for COVID-19 than non-immigrant HCWs living in Swedish-dominated neighborhoods. Conclusions Neighborhood immigrant density was associated with COVID-19 hospitalization among HCWs in Sweden. However, immigrant HCWs had a high risk of the outcome regardless of where they lived. More research is needed to identify the root causes of the excess risk among immigrant HCWs. Key messages • HCWs living in immigrant-dominated neighborhoods had an elevated risk of COVID-19 hospitalization. • This study sheds additional light on the drivers of COVID-19 inequalities among Swedish HCWs.

A U-shaped relationship between LVEF and the risk of heart failure hospitalization: a large hospital-based cohort study

Abstract Background Left ventricular ejection fraction (LVEF) is a frequently used metric for quantifying left ventricular function. Previous studies found a U-shaped relationship between LVEF and long-term survival. However, the association between the spectrum of LVEF and heart failure (HF) hospitalization remains unclear. Purpose We aim to investigate the distribution of HF hospitalizations across the spectrum of LVEF using a large hospital-based cohort. Methods Consecutive participants who underwent echocardiography (2002-2021) in a tertiary medical center in Taiwan were included. LVEF was measured by echocardiography using biplane Simpson’s method and was categorized into intervals of 5% from &amp;lt;20% to ≥70%. The study outcome was HF hospitalization by linking to the National Health Insurance Registry Database. Cox proportional hazards regression was used for analyses with adjustment for age, sex, hypertension, diabetes, hyperlipidemia, coronary artery disease, and history of HF. We used restricted cubic splines to demonstrate the distribution of HF hospitalizations across the spectrum of LVEF. Results 94,762 participants (age 59.7 ± 18.1, men 51.4%) were included. Adjusted hazard ratios (HR) for HF hospitalizations showed a U-shaped relationship between LVEF and the risk of incident HF hospitalization with a nadir of risk at LVEF of 60-70%. (Figure) Compared with the reference group (LVEF: 60-65%), subjects with LVEF&amp;gt; 70% had an HR of 1.49 (95% confidence interval [CI]: 1.21-1.84), and those with LVEF of 50-55% had an HR of 1.93 (95% CI: 1.68-2.22). Similar results with a nadir at 60-70% could be observed irrespective of different age groups defined by the World Health Organization (WHO), sex, with or without hypertension or diabetes. Conclusions A U-shaped relationship between LVEF and the risk of incident HF hospitalization can be observed, with a nadir at LVEF of 60-70%. LVEF ≥ 70% may be defined as supranormal LVEF that necessitates further HF treatment.Figure

Low levels of apolipoprotein M are associated with increased risk of ventricular arrhythmias

Abstract Background Ventricular arrhythmia (VA) is a frequent cause of sudden cardiac death (SCD). Treatment to prevent SCD includes device therapy with implantable cardioverter defibrillator (ICD). Although the electrophysiology underlying VA have been described, the molecular understanding of VA risk remains unclear. Purpose To identify proteins that are associated with higher and lower risk of VA. Methods SMASH 1 Study was a prospective observational study of 490 patients treated with ICD. The plasma proteome was analyzed with the Olink Explore 384 Cardiometabolic platform at study inclusion, and patients were followed for mean 3.1± 0.7 years. VA events were defined as adjudicated ventricular fibrillation or sustained ventricular tachycardia registered from ICD recordings and clinical events were recorded from electronic health records. Protein concentrations were quantified relatively as normalized protein expression on a log2-transformed concentrations where a large number represents higher protein level in the sample. Results The mean age was 66±12 years, 83% were male and 51% had a primary prevention ICD-indication. Episode(s) of VA occurred in 137 patients (28%) during follow-up. In total, 353 distinct proteins were successfully analyzed in all patients. Among these, high B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) levels were associated with a higher risk of VA, while Apolipoprotein M (APOM) was the only protein significantly associated with a lower risk of VA after multiple testing using Benjamini-Hochberg correction (Figure, Panel A). After adjusting for age, sex, body mass index, coronary artery disease, heart failure, renal function, left ventricular ejection fraction and antiarrhythmic medication, only low APOM levels remained significantly associated with VA: HR 0.51 (95%CI 0.32-0.79] per log unit increase, p=0.003. Patients in the lowest quartile of APOM had a particularly high risk of incident VA: HR 2.26 (95%CI 1.60-3.19), p=3.61x10-6, compared to quartile 2-4 (Figure, Panel B). High APOM levels were also associated with a lower risk of HF hospitalizations (HR 0.25 [95%CI 0.16-0.40], p&amp;lt;0.001) and all-cause mortality (HR 0.36 [95%CI 0.22-0.60], p&amp;lt;0.001), and these associations remained significant in adjusted models. Conclusions Low levels of APOM are associated with a greater risk of incident VA, independently of established risk factors. Low APOM also predicted risk of HF hospitalizations and mortality in our cohort, which suggest protective cardiovascular effects of APOM. Figure: Association of individual proteomic measures with risk of ventricular arrhythmias (VA).A:Volcano plots of the associations of individual plasma proteins with incident VA. The dotted line represents the significance level at false discovery rate &amp;lt;0.05 and the red dots are significant proteins after multiple testing using Benjamini-Hochberg correction.B: Risk of VA by quartile of Apolipoprotein M.

Amiodarone-related thyroid dysfunction and associated outcomes in patients with heart failure - a matched case-control study

Abstract Aim The association between amiodarone-related thyroid dysfunction and the risk of worsening heart failure (HF) or death has been reported with conflicting results. Methods The study cohort was patients with HF and without a history of thyroid dysfunction (defined by medical treatment or diagnosis) who initiated treatment with amiodarone in the period 1996-2021. Within this cohort, those who developed thyroid dysfunction (cases) were identified and matched 1:3 on age, sex, calendar year, duration of HF, and time since initiation of amiodarone with patients (controls) from the same cohort and followed for the primary outcome of HF hospitalization or all-cause death at 1-year, assessed by Kaplan Meier curves and Cox regression models adjusted for ischemic heart disease, chronic kidney disease, malignancy, atrial fibrillation and ventricular tachycardia. Results The study cohort comprised 21,947 patients, of whom 4,137 (19%) developed thyroid dysfunction following initiation of amiodarone. After matching, the study population consisted of 4,063 cases (mean age 69 years, 68% men, 41.6% developed thyroid dysfunction within the first year after initiation of amiodarone) and 10,940 matched controls, (Figure 1). The index date was the date of thyroid dysfunction for cases, and for matched controls a date at a similar distance since amiodarone initiation. At 1-year follow-up, the primary outcome occurred in 1,543 (38.0%) cases and 3,681 (33.6%) matched controls (reference), adjusted hazard ratio (HR) 1.13 (95%, confidence interval CI 1.07-1.20), although this was solely driven by HF hospitalization (28.9% vs 21.8%; HR 1.32 (95% CI 1.23-1.41), whereas all-cause death was lower among cases (18.2% vs. 20.4%, HR 0.85 (95% CI 0.78-0.93), (Figure 2). Conclusions Among HF patients treated with amiodarone, the development of thyroid dysfunction was associated with an increased risk of HF hospitalization or all-cause death, but this was solely driven by the excess risk of HF hospitalization, whereas it was associated with a lower risk of all-cause death. The absence of excess mortality indicates that thyroid complications are manageable in this vulnerable population of patients with HF.Figure 1 Flowchart of the populationFigure 2 Cumulative risk

Environment, climate, socio-economics &amp; restrictions impact on COVID-19 in Northen Italy

Abstract Up to now, studies on environmental, climatic, socio-economic factors, and non-pharmacological interventions (NPI) show diverse associations, often contrasting, with COVID-19 spread or severity. Most studies used large-scale, aggregated data, with limited adjustment for individual factors, and most of them focused on viral spread rather than severe outcomes. Moreover, evidence simultaneously evaluating variables belonging to different exposure domains is scarce, and none analysing their collective impact on an individual level. Our population-based retrospective cohort study aimed to assess the comprehensive role played by exposure variables belonging to four different domains, environmental, climatic, socio-economic, and non-pharmacological interventions (NPI), on individual COVID-19-related risk of hospitalization and death, analysing data from all patients (n.68472) tested positive to a SARS-CoV-2 swab in Modena Province (Northern Italy) between February 2020 and August 2021. Using adjusted Cox proportional hazard models, we estimated the risk of severe COVID-19 outcomes, investigating dose-response relationships through restricted cubic spline modelling for hazard ratios. Several significant associations emerged: long-term exposure to air pollutants (NO2, PM10, PM2.5) was linked to hospitalization risk in a complex way and showed an increased risk for death; while humidity was inversely associated; temperature showed a U-shaped risk; wind speed showed a linear association with both outcomes. Precipitation increased hospitalization risk but decreased mortality. Socio-economic and NPI indices showed clear linear associations, respectively negative and positive, with both outcomes. Our findings offer insights for evidence-based policy decisions, improving precision healthcare practices, and safeguarding public health in future pandemics. Refinement of pandemic response plans by healthcare authorities could benefit significantly. Key messages • Evaluating simultaneously four exposure domains on COVID-19 outcomes informs public health policy for future pandemic management. • The comprehension of risk factors associated with severe outcomes, such as hospitalization and mortality, is pivotal for planning responses to similar health emergencies in the future.

Association of osteopontin and shrunken pore syndrome with hospitalization for renal failure in acute heart failure patients

Abstract Background Shrunken pore syndrome (SPS) emerges as a distinctive manifestation of glomerular filtration dysfunction mainly manifested by the impairment of moderate-sized molecular filtration, distinguished by a variance in renal filtration between cystatin C and creatinine. SPS exhibits correlations with adverse prognosis of various cardiovascular diseases. A decline in renal function correlates with a poor prognosis among individuals with heart failure (HF). Osteopontin (OPN), a protein involved to bone mineralization, has been linked to deteriorating renal function and heightened risk for adverse outcomes in patients with chronic kidney disease. Purpose To explore if OPN and SPS are associated with hospitalization for renal failure in patients with acute HF. Methods Cystatin C and creatinine were analyzed in 395 hospitalized HF patients, of which 324 also had osteopontin (OPN) analyzed using a proximity extension assay. SPS was calculated using the CKD-EPI Equations for Glomerular Filtration Rate and defined as a cystatin C-based estimated glomerular filtration rate (eGFR) &amp;lt;60% of the creatinine based eGFR. Hospitalization for renal failure was extracted from regional registries using ICD10 codes N17-N19. Logistic and Cox regression models were deployed to explore a) OPN’s association with SPS; b) OPN’s association with hospitalization for renal failure; and c) SPS’s association with hospitalization for renal failure, adjusting for age, sex, systolic blood pressure and use of renin-angiotensin-aldosterone system (RAAS) inhibitors. Results The study population had a mean age of 74.8 (±12.0) years, 32.4% were women and 104 (26.5%) patients presented with SPS (Table 1). During the median follow-up period of 71 (interquartile range 56-88) months, 35 (8.9%) patients were hospitalized for renal failure. OPN was associated with the prevalence of SPS (OR 1.66; 95%CI 1.08-2.27; p=0.002), as well as with higher risk of hospitalization due to renal failure (HR 2.71; 95%CI 1.61-4.56; p&amp;lt;0.001). Further, also prevalent SPS was associated with higher risk of hospitalization due to renal failure (HR 2.44; 95%CI 1.14-5.24; p=0.022). Conclusions Here, we demonstrate that higher OPN levels are associated with a higher prevalence of SPS and an elevated risk of hospitalization due to renal failure among patients with HF. Additionally, the presence of SPS was associated with a higher risk of renal failure-related hospitalizations. These findings highlight the potential utility of OPN and SPS as biomarkers for identifying heart failure patients at risk of renal function decline, underscoring the importance of early risk stratification and targeted interventions in this population.

Atrial Fibrillation (AF) detected by repeat handheld ECG screening and the risk of heart failure hospitalization

Abstract Purpose Heart failure and atrial fibrillation (AF) frequently complicate one another. Risk of heart failure in screen-detected patients was not investigated. We aimed to compare risk of hospitalization for heart failure (HHF) between screen-detected and clinically-diagnosed AF, and to evaluate the impact of AF burden. Methods Consecutive patients aged over 65 attending outpatient clinics were prospectively recruited for AF screening, using handheld single-lead ECG (AliveCor) during December 2014 and December 2017. Patients who had &amp;gt;1 visits received repeat screening. All participants were divided into 5 cohorts: (i) previously known AF at enrolment; (ii) initial screen-detected AF; (iii) subsequent screen-detected AF; (iv) clinically-diagnosed AF during follow-up (FU); (v) No AF. Risk of HHF was estimated by adjusted sub-distribution hazard ratios (aSHR) derived from Fine and Gray regression, accounting for death as competing risk, adjusting for CHA2DS2VASC components and chronic kidney disease, AF diagnosis being handled as time-dependent variable. Patients who participated in repeat screening and previously known AF formed a sub-cohort. Patients with previously known AF who were in AF in the initial screening and those with repeat screen-positivity were defined probably persistent AF, otherwise paroxysmal AF (single screen-positivity) or no AF (never screen-positive). Risk of HHF was compared between groups stratified by AF burden (persistent vs. paroxysmal) and scenario of AF diagnosis (screen-detected vs. clinically-diagnosed). Results Of 11,972 subjects (mean age 76.6±7.8, female 49.2%), 18.7% (n=2,236) had known AF, 1.9% (n=223) initial screen-detected AF, 0.6% (n=71) subsequent screen-detected AF, 7.3% (n=867) clinically-diagnosed AF during FU, and 71.6% (n=8,559) no AF. During a median FU of 6.7 (IQR:4.4-8.0) years, risk of HHF was highest in patients with clinically-diagnosed AF (aSHR=3.5(2.7-4.5)), followed by subsequent screen-detected AF (aSHR=2.8(1.6-5.0)), previously known AF (aSHR=1.9(1.6-2.2)), and initial screen-detected AF (aSHR=1.7(1.1-2.4)) (Figure 1a). Sensitivity analysis excluded those with known heart failure at baseline, after which risk of HHF became comparable between previously known and initial screen-detected AF (Figure 1b). Sub-analysis for participants (32.2% (n=3,853), mean age 76.7±7.3, female 47.5%) of repeat screening showed screen-detected persistent AF (aSHR=3.7(1.9-7.2)) was at highest risk of HHF, followed by clinically-diagnosed AF (AF burden unassessed) (aSHR=3.3(2.2-5.0)), previously known persistent AF (aSHR=3.1(2.5-3.8)), screen-detected paroxysmal AF (aSHR=2.1(1.4-3.4)), previously known paroxysmal AF (aSHR=1.8(1.3-2.4) (Figure 1c). Conclusion Higher AF burden and FU new AF diagnosed by either screening or clinic visit was associated with higher risk of HHF. Screening facilitating early AF diagnosis and early downstream intervention, warranted further study.

Social health gradient and risk factors among patients hospitalized for COVID-19 and pre-pandemic respiratory infections. A linked national individual case-control study in Belgium.

The literature establishes a clear social gradient in health for transmissible respiratory diseases. However, this gradient's extent remains largely unexplored in the context of COVID-19, and it is uncertain whether the pandemic has exacerbated this gradient. The study aims to compare the socio-economic profiles and comorbidities during the COVID-19 pandemic with a control population affected by viral pneumonia/respiratory disease in 2019. This case-control study analyzed linked data from all patients hospitalized for COVID-19 in 2020 (n = 22,087) and for respiratory diseases in 2019 (n = 7,586). Socio-economic data from the social security database were linked to clinical data from the hospital registry. We analyzed the socio-demographic and clinical factors associated with COVID-19 hospitalization (control group, wave 1, and wave 2) using multinomial regressions and logistic regression models and the length of stay during hospitalization using binomial negative regressions. A social health gradient was observed in both the COVID-19 and control groups, with a significant increase across waves for COVID-19 (p-trend < 0.0001). Men, people over the age of 45, those with comorbidities, high population density, lower income, lower socio-economic status, and people living in Brussels capital were at higher risk of COVID-19 hospitalization and longer length of stay compared to the control group. Except for sub-Saharan Africans, all patients of foreign nationality had a significantly increased risk of hospitalization (p < 0.001), but a shorter length of stay compared to Belgians. The socio-health gradient for COVID-19 followed the same pattern as that observed in pre-pandemic respiratory diseases, intensifying in the second wave and among the most deprived groups. This study emphasizes the importance of collecting social data alongside clinical data for a better understanding of social health inequalities and for tailoring health prevention policies.