bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex differences in long-term outcomes among hospitalized heart failure patients across the spectrum of ejection fraction: findings from the Get with the guidelines - heart failure registry
Authors: Keshvani N , Shah S , Ayodele I , Chiswell K , Alhanti B , Allen L , Sharma K , Greene S , Yancy C , Van Spall H , Fonarow G , Heidenreich P , Pandey A 
Published: November 2023

Abstract

Background
Sex differences in 5-year outcomes across heart failure (HF) ejection fraction (EF) subtypes are not well known.

Purpose
To assess the interaction between sex and EF for risk of long-term adverse outcomes after hospitalization with HF.

Methods
Patients from American Heart Association’s Get With The Guidelines – Heart Failure registry enrolled between 1/1/2006 – 12/31/2014 with age ≥ 65 years with available 5-year follow-up data, ascertained through linkage with Medicare fee-for-service Part A administrative claims, were included. HF subtypes included HF with reduced EF (HFrEF) with EF ≤ 40%, HF with mildly reduced EF (HFmrEF) with EF 41-49%, and HF with preserved EF (HFpEF) with EF ≥ 50%. Sex differences in 5-year all-cause mortality and readmission for each HF subtype were assessed using unadjusted cumulative incidence methods and adjusted Cox models. Median survival across HF subtypes was compared to median survival of U.S. adults.

Results
155,670 patients (mean age 81 years, 53.4% females) were included. Male patients were younger and had a higher prevalence of prior myocardial infarction or coronary artery bypass graft surgery and were more likely to have HFrEF, while women were more likely to have history of hypertension and HFpEF. The median post-hospitalization survival of patients with HF was substantially lower than the age- and sex-specific U.S. life expectancy across each HF subtype (Figure 1).Patients with HF had high 5-year mortality rates (HFrEF male: 81.3%, female: 78.4%; HFpEF male: 80.5% vs female 79.5%). In adjusted analysis, female (vs. male) patients had a significantly lower 5-year mortality risk (HR [95%CI]: 0.89 [0.87 – 0.90], p&lt;0.01) and a higher 5-year readmission risk (all-cause: 1.03 [1.02 – 1.04]), CV: 1.05 [1.04 – 1.07]), HF: 1.06 [1.04 – 1.08], p&lt;0.01 for each). HF subtype modified the association between sex and 5-year outcomes (pinteraction &lt;0.05 for mortality and CV and HF readmission), with the greatest risk reduction of mortality for female vs. male patients with HFrEF and the greatest risk increase of readmission (CV and HF) among female vs. male patients with HFmrEF and HFpEF (Figure 2).

Conclusion
Among patients with HF, the overall survival post-HF hospitalization is very low for each HF subtype. Female patients have a lower 5-year mortality risk but a higher risk of HF or CV readmission regardless of EF.Figure 1Figure 2
Usefulness of Neutrophil-to-Lymphocyte Ratio (NLR) in predicting adverse outcomes in adult patients with heart failure : A systematic review and meta analysis
Authors: Mondal A , Patel B , Pingili A , Katukuri N , Bhanushali A , Vyas A , Jain A , Desai R 
Published: November 2023

Abstract

Background
Inflammation plays a potential role in heart failure (HF) etiology and prognosis. Neutrophil-to-Lymphocyte ratio (NLR) is a simple, routinely available lab criteria. In this meta-analysis, we sought to investigate the role of NLR on HF outcomes which remains unexplored.

Methods
PubMed, Embase and Scopus were systematically screened to find studies through August 2022, reporting data on association of HF related outcomes [all-cause mortality (ACM), cardiovascular (CV) death, in-hospital, HF readmissions and composite events] and NLR. Random effects models and I2 statistics were used to estimate pooled odds of outcomes and heterogeneity. Leave one out sensitivity analysis was performed.

Results
A total of 11 studies (6 retrospective and 5 prospective, 4 studies from Asia and Europe each, 2 from the US and 1 multicenter study) including 12954 patients (mean age: 69 years, Males 57.2%) from 2011 to 2022 with an average follow up duration of 54.8 months were included. Elevated NLR was significantly associated with ACM (aOR 1.80, 95%CI 1.46-2.22, p&lt;0.01, Table 1), HF readmissions (aOR 2.53, 95% CI 1.60-3.99), in-hospital mortality (aOR 3.26, 95% CI 1.76- 6.02), CV mortality (aOR 1.84, 95%CI 1.03-3.31) and composite CV outcome including heart transplant (OR 2.07, 95% CI 1.32-3.25), p&lt;0.001.

Conclusion
Elevated NLR was significantly associated with worse outcomes in HF patients. The NLR test might potentially be useful in identifying high-risk HF patients and curtail worse outcomes.
Impact of eGFR slope upon mortality in a real world heart failure cohort
Authors: Moya A , Oeste C , Beles M , Masuy I , Verstreken S , Dierckx R , Heggermont W , Goethals M , Bartunek J , Vanderheyden M 
Published: November 2023

Abstract

Background
Heart failure (HF) frequently causes an imbalance in heart and kidney functions, and the prognosis of heart and kidney disease can worsen one another. In addition to the prognostic role of chronic kidney disease (CKD), dynamic changes in renal function have been recognized to portend a poor prognosis in HF patients.

Purpose
This study aimed to investigate the prevalence of impaired renal function at HF diagnosis and its association with short and long-term outcomes in a real-world cohort of HF patients. In addition, we assessed how dynamic changes in renal function after HF diagnosis might predict HF prognosis.

Methods
Using a natural language processing algorithm, clinical data of patients with at least one diagnosis of HF (index event) were retrospectively collected. Patients for which the most recent estimated glomerular filtration rate (eGFR) value prior to the index date was ≤ 60 mL/min/1.73m2 and/or had a documented medical history of CKD (including dialysis) were considered as having CKD. A linear mixed effects model was used to show the longitudinal eGFR trajectories during the follow-up period (after index). A Cox proportional hazard model was used to analyse the association between baseline variables and mortality. Finally, joint modelling was used to combine the linear mixed eGFR sub-model with the survival sub-model, to estimate the effect of the current eGFR value and the eGFR slope of the year prior on mortality.

Results
The study population consisted of 1992 patients with a mean (±SD) age of 74.8 ± 11.7 years and 58% males. In total, 17% had HF with preserved ejection fraction (HFpEF, n = 339) and 70% (n = 1156) presented CKD at the index event. The median follow-up time was 3.16 years and 13% (n = 198) of the patients were deceased after two years. The group of 2-year survivors had significantly lower proportion of CKD at index (55 vs 76%, p &lt; 0.001). The calculated mean yearly decrease of the eGFR value was 4.2 mL/min/1.73m². The multivariate Cox PH model identified age, CVA, diastolic blood pressure, HDL, and log10proBNP as baseline predictors of mortality. Joint modelling showed that a 10 mL/min/1.73m2 lower current eGFR value amongst patients was associated with an increased mortality hazard of 1.30 ± 0.06 (p &lt; 0.001). Additionally, a decrease of 10 mL/min/1.73m2 in eGFR during the year prior indicated an increased mortality hazard of 1.87 ± 0.19 (p &lt; 0.001).

Conclusion
In a real-world cohort of HF patients, the prevalence of CKD is high and CKD is an independent predictor of mortality. The current eGFR value and the year prior’s eGFR slope adds additional prognostic information and helps to better fine tune the individual mortality hazard. Based on the findings of this analysis, patients with worse prognosis might benefit from a closer and more vigilant follow-up.
Effect of timely availability of TTR-stabilizing therapy on diagnosis, treatment initiation, and cardiovascular outcomes in transthyretin amyloid cardiomyopathy
Authors: Dobner S , Stortecky S , Wiedemann S , Kassar M , Pilgrim T , Graeni C , Hunziker L , Bernhard B 
Published: November 2023

Abstract

Background
Transthyretin-stabilization reduces cardiovascular morbidity and mortality in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). Despite increased access, regional differences in the availability of therapy continue to exist, and how these may affect diagnostic efficacy and cardiovascular outcomes is currently unknown.

Objective
To determine how access to and availability of tafamidis affected time-to-diagnosis, time-to-therapy, and cardiovascular outcomes in patients with ATTR-CM.

Methods and Results
91 consecutive patients diagnosed with ATTR-CM between June 2019 and June 2021 were evaluated for TTR-stabilizing therapy with tafamidis. Access was regulated by an expanded access program for the initial 42 patients (early cohort; 46.2%), while insurance coverage was required for the latter 49 patients (facilitated access cohort, 53.8%) after local regulatory drug approval in April 2020. Tafamidis was started in 37 of 42 (88.1%), and 43 of 49 patients (87.8%), respectively. Baseline characteristics, e.g., age (76.3±6.4 vs. 77.3±6, p = 0.45), sex (male: 95.2% vs. 93.9%) and ATTR-CM disease stage (≤stage 2: 88.2% vs. 90.9%, p= 0.919) were comparable between both groups.
Timely availability of tafamidis after April 2020 numerically reduced time from first presentation to diagnosis (median [months (IQR)]) from 6.2 (1.3;28.9) to 2.4 (0.7; 21.7) months (p = 0.196) and from presentation to therapy from 24.4 (10.7;46.8) to 11.8 (6.4; 32.4) months (p = 0.127). While RV function assessed by echocardiography significantly decreased in the early cohort between diagnosis and therapy initiation (S’ velocity 10±2.2 to 9.2±2.2 cm/s; p = 0.018; TAPSE 17.3±4.7 to 15.7±3.9, p = 0.008) it remained stable in the facilitated access cohort (S’ velocity 9.56±2.57 to 9.36±2.28 cm/s; p = 0.83; TAPSE 15.6±4.2 to 16.3±3.1, p = 0.45). After a median follow-up 42.3 and 24.9 months in the early and facilitated access cohort, respectively, timely availability of tafamidis in the facilitated access cohort was associated with a significant reduction of annual heart failure hospitalisations (treated: 0.12±0.34 vs. 0.5±1, p = 0.049; overall cohort: 0.17±0.37 vs. 0.35±0.47, p = 0.044). Overall, timely diagnosis of ATTR-CM within 12 months of first presentation was associated with a significant reduction in all-cause mortality [HR = 3.490 (95% CI 1.37 to 8.91), p = 0.009], prolonged survival without MACE [HR = 2.50 (95% CI 1.30 to 4.81), p = 0.006] or heart failure hospitalisation [HR = 2.52 (95% CI 1.24 to 5.16), p = 0.011].

Conclusions
Availability of tafamidis numerically shortened time-to-diagnosis and time-to-therapy initiation in ATTR-CM patients. Timely diagnosis and initiation of therapy was associated with a reduction in all-cause mortality and heart failure hospitalisations.Door-to-diagnosis-therapyClinical outcomes
Lower incidence of new-onset heart disease following covid-19 compared to viral pneumonia despite more echocardiography
Authors: Ovrebotten T , Tholin B , Myhre P L , Stavem K 
Published: November 2023

Abstract

Background
Studies have shown an increased risk of cardiac disease and dysfunction following COVID-19. However, it remains unknown whether infection with COVID-19 differs from other viral pneumonias with respect to subsequent incident heart disease.

Purpose
To determine the incidence of heart disease and use of cardiac procedures in patients following a diagnosis of COVID-19 compared to other viral pneumonias.

Methods
In a retrospective, observational study, we compared incidence rates for cardiac disease diagnosed after hospitalization with COVID-19 February-November 2020 versus hospitalization with viral pneumonia as the main diagnosis in 2018-2019. Data was obtained from The Norwegian Patient Registry and the Norwegian Surveillance System for Communicable Diseases, and linked with a unique national person identification number. We defined heart disease using ICD-10 codes and used Cox regression models to compare the hazard of first episodes of myocarditis, acute myocardial infarction, atrial fibrillation/flutter, heart failure, ischemic disease, other cardiac disease, and total heart disease (any of these conditions). Patients were followed until 31 December 2020, with censoring on this date or a maximum of 274 days after hospital admission.

Results
Patients hospitalized with COVID-19 in 2020 (n = 2,359) were younger, mean 59 (SD 18) vs 69 (19) years, had fewer comorbidities, had fewer hospitalizations prior to the index hospitalization (0.5 (1.2) vs 0.9 (1.8)), were more frequently treated with respiratory support (14.2% vs 7.8%) and had higher in-hospital mortality (6.9% vs 2.3%) than patients hospitalized with viral pneumonia in 2018-2019 (n = 9,018). Patients hospitalized with COVID-19 had a lower crude incidence of new total heart disease than those with viral pneumonia (56 [95%CI 48-65] vs 75 [95%CI 71-79] per 100,000 person-years). This difference persisted after adjusting for age, sex, Charlson comorbidity score (comprising age, sex, and 17 dichotomized comorbidities), hospital admission during the previous year, respiratory support, and a propensity score for being hospitalized for COVID-19 vs. other pneumonia: Hazard ratio (HR) 0.79 [95%CI 0.67-0.94], p = 0.006. Patients with COVID-19 more frequently underwent echocardiography: HR 1.41 [1.23-1.63], p = &lt;0.001 (Fig. 1).

Conclusion
Following hospitalization for COVID-19, the incidence of total heart disease and heart failure was lower than for patients hospitalized with viral pneumonia, despite more frequent examinations with echocardiography.Figure 1
Importance of early diagnosis and treatment of heart failure across the spectrum of ejection fraction
Authors: Wang H , Gao C , Guignard-Duff M , Cole C , Hall C , Larman M , Baruah R , Gao H , Mamza J B , Lang C C , Mordi I 
Published: November 2023

Abstract

Introduction
Early diagnosis of heart failure (HF) is crucial in ensuring that optimal guideline-directed medical therapy (GDMT) is administered to reduce morbidity and mortality. Limited access to echocardiography could lead to late diagnosis for patients, for example during a HF hospitalisation (hHF).

Purpose
The study aimed to compare the incidence and outcomes of inpatient versus outpatient diagnosis of HF across the ejection fraction (EF) spectrum.

Methods
Electronic health records were linked to echocardiography data between 2016 to 2021. Diagnosis of incident HF was classified into inpatient (hHF) or outpatient (echocardiography reporting impaired left ventricular function or preserved EF with at least 2 continuous prescriptions of loop diuretics) and stratified by EF to define HF with reduced/mildly reduced/preserved EF (HFrEF/HFmrEF/HFpEF). A non-HF comparator group with normal LV function was also defined. The primary outcome was time to CV death or hHF.

Results
5251 individuals were identified, 1100 HFrEF, 650 HFmrEF, 1252 HFpEF, 1295 HF with unknown EF, and 954 non-HF comparators. Median duration of follow-up was 2.4 years. CV death or hHF were observed in 605 individuals (55%) with HFrEF, 237 (36%) with HFmrEF, 333 (27%) with HFpEF, 98 (10%) of non-HF comparators, and 647 (50%) with HF but unknown EF. Compared to non-HF individuals, HF patients had significantly worse outcome (hazard ratio [HR] adjusted for age and sex – HFrEF: 8.22 [95% CI: 6.64 – 10.18], p &lt; 0.001; HFmrEF: 4.40 [3.47 – 5.58], p &lt; 0.001; HFpEF: 2.89 [2.31 – 3.62], p &lt; 0.001; HF with unknown EF: 8.22 [6.64 – 10.18], p &lt; 0.001). Of the 4297 HF patients, 2318 (54%) were diagnosed as inpatients, an increase from 42% in 2016 to 62% in 2021. Those diagnosed as inpatients had significantly worse outcome than those diagnosed as outpatients (adjusted HR: 1.83 [1.66 – 2.01], p &lt; 0.001). This difference was driven by those with HFpEF (adjusted HR: 2.31 [1.80 – 2.96], p &lt; 0.001), but was not seen in HFrEF (1.05 [0.89 – 1.23], p = 0.554) or HFmrEF (0.97 [0.73 – 1.28], p = 0.811). For HFrEF patients first diagnosed as inpatients, those discharged on GDMT had a reduced incidence of the primary outcome: adjusted HR compared to those discharged on no GDMT drugs - monotherapy 0.77 [0.51 - 1.16], p = 0.205; dual-therapy 0.57 [0.37 – 0.88], p = 0.011; and triple therapy 0.54 [0.33 – 0.90], p = 0.017.

Conclusion
Individuals whose first presentation of HF was a HF hospitalisation had a significantly worse outcome than those who were diagnosed in the community. These real-world data also demonstrate the benefit of early optimisation of GDMT during a hHF. Our results highlight the importance of improving diagnostic pathways to allow for earlier identification and treatment of HF across the ejection fraction spectrum.Outcomes Based on Diagnostic LocationImpact of GDMT After Hospitalisation
Impact of integrated care in patients with heart failure with reduced ejection fraction: a report from the WARCEF trial
Authors: Proietti M , Romiti G F , Bonini N , Corica B , Mei D A , Qian M , Thompson J L P , Homma S , Lip G Y H 
Published: November 2023

Abstract

Background
In recent years there has been more and more attention to the concept of ‘integrated care’ for patients with cardiovascular diseases. Integrated care strategies have been thought to provide comprehensive evaluation and management of patients characterized by complex chronic conditions and high prevalence of comorbidities.

Purpose
To propose and evaluate an integrated care management for patients with heart failure with reduced ejection fraction (HFrEF).

Methods
We performed a secondary analysis of the WARCEF trial, which randomized HFrEF patients with sinus rhythm at baseline to Warfarin and Aspirin. We propose the ABC-HF as a strategy of integrated care management. ABC-HF stands on three pillars: i) Adherence to Guideline-Directed-Medical-Therapy, defined as ACE inhibitors/ARBs plus Beta-Blockers plus MRAs; ii) Better symptom control, defined as NYHA category I-II; iii) Comorbidities optimisation, as per guideline-directed management of hypertension, previous myocardial infarction, previous stroke, peripheral vascular disease, (incident) atrial fibrillation, etc. Patients were managed adherent to the ABC-HF strategy if all the three conditions were fulfilled. Main outcome was the composite of ischemic stroke, intracranial hemorrhage, all-cause death.

Results
A total of 2,264 patients were available for analysis (mean [SD] age 60.8 [11.4] years, 450 [19.9%] females). Overall, 254 (11.2%) patients were managed adherent to ABC-HF: 199 (8.8%) adherent to no criteria; 905 (40.0%) to one criterion; and 906 (40.0%) to two criteria. Over a mean (SD) follow-up of 3.55 (1.78) years there were 602 (26.6%) events. Patients managed adherent to ABC-HF reported a lower rate of composite outcome compared to those non-adherent (16.1% vs. 27.9%, p&lt;0.001). A Cox multivariate regression analysis adjusted for age, sex, ejection fraction, randomized treatment, and Minnesota physical domain score showed that clinical management adherent to ABC-HF was associated with a reduction in the risk of the primary composite outcome (HR 0.54, 95% CI 0.38-0.76). A progressively higher number of ABC-HF criteria fulfilled was associated with a progressively lower risk [Figure 1].

Conclusion
In a cohort of HFrEF with severe ventricular dysfunction, adherence to ABC-HF, as an integrated care management for HF patients, is associated with a lower risk of adverse outcomes. Higher numbers of ABC-HF criteria fulfilled is associated with a progressively lower risk.ABC-HF Criteria and Risk of Composite Ou
Validation of the ATTR-CM score for transthyretin amyloid cardiomiopathy in a mediterranean cohort of patients at risk
Authors: Cediel G , Santesmases J , Domingo M , Moragas G , Sola M , Garcia-Calvo X , Guix G , Pacho C , Santiago-Vacas E , Borrellas A , Codina P , Figuerola N , Ruiz-Cueto M , Lupon J , Bayes-Genis A 
Published: November 2023

Abstract

Background
Transthyretin Amyloid Cardiomiopathy (ATTR-CM) is an emerging underdiagnosed cause of heart failure. 99mTc-3, 3-diphosphono-1,2-propanodicarboxylic acid (DPD) allows ATTR-CM diagnosis in the absence of histology. Recently a simple clinical score to identify increased risk of ATTR-CM in patients with heart failure and preserved left ventricular ejection fraction has been developed and validated.

Purpose
To assess the prevalence of ATTR-CM in a Mediterranean cohort of patients at risk, and to externally validate the ATTR-CM score. We also explore its diagnostic accuracy improvement by adding N-terminal pro-B-type natriuretic peptide (NTproBNP).

Methods
Retrospective cohort study of consecutive patients with suspected cardiac amyloidosis referred to DPD planar test between March 2017 and November 2020. Scans were reported using a visual grading system (0 to 3 increasingly; 2-3 positive) on planar images (anterior, left oblique anterior and lateral). Patients with clonal dyscrasia or those without rule-out tests (serum free light chain assay, and serum and urine protein electrophoresis with immunofixation) were excluded. Discrimination was obtained using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve based on the ATTR-CM score [High risk: score ≥ 6. Components and punctuation: age (60-69 = 2 points; 70-79 = 3 points; ≥80 = 4 points), male sex = 2 points, hypertension diagnosis = -1 point, ejection fraction &lt;60% = 1 point, posterior wall thickness ≥12 mm = 1 point, relative wall thickness (septal + posterior wall thickness/left ventricular end diastolic diameter) &gt;0.57 = 2 points]. Calibration was assessed with the Hosmer-Lemeshow goodness- of-fit test.

Results
A total of 200 patients were included with a mean age of 78.5 ± 11 years, 45.5% male, left ventricular ejection fraction 58%±12 and a median NTproBNP of 2310 pg/ml (Figure 1). 81 (40.5%) patients were categorized as a high-risk group due to score value ≥6. Prevalence of ATTR-CM was 36%. The AUC for ATTR-CM score in our cohort was 0.82 (95% CI 0.75-0.89) with an appropriated calibration (Figure 2). The addition of NTproBNP to the score did not increase the AUC (P = 0.18), with a Net Reclassification Improvement (NRI) of 0.013 (95% CI - 0.102 to 0.210).

Conclusion
A simple clinical score is a valid and reliable tool for ATTR-CM diagnosis in our Mediterranean cohort. Added to clinical suspicion, it can improve the diagnostic workup for ATTR-CM, irrespective of NTproBNP values.Demographic and clinical characteristicsAUC of ATTR-CM score in our cohort