bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine learning to improve the performance of natriuretic peptides across age groups for the diagnosis of acute heart failure
Authors: Perez Vicencio D , Doudesis D , Thurston A J F , Lee K K , Mills N L 
Published: October 2024

Abstract

Background
Guidelines recommend N-terminal pro-B-type natriuretic peptide (NT-proBNP) thresholds for the diagnosis of acute heart failure but performance of these thresholds in different age groups is uncertain and could be improved using machine learning methods that incorporate age as a continuous measure.

Purpose
To evaluate the diagnostic performance of guideline-recommended NT-proBNP thresholds for different age groups and a validated decision-support tool using machine learning for the diagnosis of acute heart failure.

Methods
NT-proBNP concentrations and the output from the CoDE-HF decision-support tool that uses machine learning to combine NT-proBNP and age as continuous variables with other patient variables were determined in 10,369 patients (median age 73 [interquartile range 59-82]) with suspected acute heart failure pooled from fourteen studies. The diagnostic performance of guideline-recommended NT-proBNP uniform rule-out thresholds (300 pg/mL), and age-stratified rule-in thresholds (450 pg/mL, 900 pg/mL and 1,800 pg/mL for &lt;50, 50-75 and ≥75 years, respectively) and CoDE-HF were evaluated using random effects meta-analysis across patient age groups.

Results
Overall, 43.9% (4549/10 369) of patients had an adjudicated diagnosis of acute heart failure. The negative predictive value (NPV) of the rule-out threshold of 300 pg/mL was lower in patients with increasing age (NPV 88.2% [confidence interval (CI) 83.5-91.8%] ≥75 years versus 98.9% [97.6-99.5%] &lt;50 years) (Figure 1). Conversely, the positive predictive value (PPV) of age stratified rule-in thresholds was lower in younger patients (PPV 61.8% [55.9-67.4%] &lt;50 years versus 80.5 % [71.1-87.4%] ≥75 years) (Figure 2). CoDE-HF had improved diagnostic performance compared to NT-ProBNP thresholds for all age groups, with the lowest NPV and PPV being 96.4% (93.8-97.9%) and 78.6% (59.8-90.0%), respectively.

Conclusion
The diagnostic performance of guideline recommended thresholds of NT-proBNP to rule-in and rule-out acute heart failure varies significantly with age. A decision-support tool that incorporates NT-proBNP with age as continuous variables provides a more consistent and accurate approach.Figure 1.Negative predictive valueFigure 2.Positive predictive value
Impact of global longitudinal strain and anemia for predicting cardiovascular mortality in patients hospitalized for acute heart failure with atrial fibrillation
Authors: Yamamoto J , Hayama H , Enomoto Y , Yamamoto M , Hara H , Hiroi Y 
Published: October 2024

Abstract

Background
Iron deficiency is a prognostic factor in heart failure (HF) with reduced ejection fraction (EF). In patients with atrial fibrillation (AF) and HF, left ventricular EF (LVEF) measurements are imprecise due to irregular tachycardia, but it is unclear whether global longitudinal strain (GLS) and anemia assessment are prognostic.

Purpose
We examined whether GLS and anemia predict cardiovascular death (CD) in patients with acute HF complicated by AF.

Methods
We retrospectively enrolled patients aged 18 years or older with acute HF complicated by AF who were consecutively admitted to our hospital from January 2014 to December 2018. Exclusion criteria were acute coronary syndromes, no transthoracic echocardiogram performed within 30 days before or after admission, and missing data. All patients were followed up from admission to CD (due to myocardial infarction, HF, stroke or sudden death), or were censored at the date of last contact or 3 years. Anemia was defined as hemoglobin &lt; 12 g/dL in females and hemoglobin &lt; 13 g/dL in males. Patients were divided into four groups according to median GLS and anemia status.

Results
A total of 320 patients (mean age 79 ± 12 years, 163 females) were included in the analysis. The median duration of AF was 1.2 years; 11% (36/320) had paroxysmal AF. The median brain natriuretic peptide value was 623 pg/ml, and 52% of the patients (165/320) were in New York Heart Association functional class 4. During a median follow-up of 528 days, 24% (77/320) patients were observed with CDs: 2 myocardial infarctions, 51 HF-related deaths, 6 strokes, and 18 sudden cardiac deaths. At the 3-year follow-up, the survival rate by the Kaplan-Meier curve was 89% (95% confidence interval (CI) 76%-95%) in the no anemia group with high GLS (&lt; -10%) and 40% (95% CI 25%-54%) in the anemia group with low GLS (≥ -10%) (p &lt; 0.001, log-rank test). In multivariate Cox regression analysis, GLS (adjusted hazard ratio (aHR) 1.06, 95% CI 1.01-1.14, p = 0.017) and hemoglobin (aHR 0.85, 95% CI 0.76-0.96, p = 0.009) were independent factors for CD, with a significantly increased risk in the anemia group with low GLS compared to the no anemia group with high GLS (aHR 4.11, 95% CI 1.59-10.6, p = 0.004). The results were consistent with no interaction by gender or LVEF 50%.

Conclusions
Anemic patients with low GLS with AF and HF may have poor prognosis. Prospective studies are needed to determine whether iron supplementation improves prognosis in such patients.
Enhancing the selection of heart failure patients for invasive procedures: how machine learning can predict the diagnostic yield of endomyocardial biopsy
Authors: Basile C , Bollano E , Rawshani A , Ljungman C , Polte C , Karason K , Bobbio E 
Published: October 2024

Abstract

Background
Determining the etiology of heart failure (HF) is crucial for appropriate treatment. Endomyocardial biopsy (EMB) is an invasive procedure that complements clinical assessment and imaging in diagnosing various cardiac disorders. The diagnostic value of EBM depends upon the anticipated yield of the procedure. Whether results from non-invasive examinations may predict the diagnostic yield from EMB is unclear.

Purpose
We aimed to investigate the relative importance of clinical and instrumental features in predicting a diagnostic EMB result, using a machine learning (ML) approach.

Methods
We retrospectively examined 665 consecutive adult patients with HF symptoms who underwent right EBM as part of their diagnostic work-up. The primary outcome was a positive biopsy result with a clear diagnosis. The ML algorithm consisted of Gradient Boosting Machines (GBM), with computation of relative variable importance using conditional importance. We calculated the conditional variable importance for 53 clinical or instrumental variables. Model performance was evaluated using a receiver operating characteristic curve, which was compared to a logistic regression model using the same variables. Validation was performed using a 10-fold cross-validation model.

Results
Among the 665 patients (50±14 years, 67% male), the EMB provided a diagnosis in 138 cases (20.8%). Patients attaining diagnosis were more often older, had a shorter disease duration, presented with ventricular arrhythmia or cardiac arrest, had a pacemaker or defibrillator, displayed higher creatinine, NT-proBNP and high-sensitive troponin T levels, and had smaller ventricular volumes with higher ejection fraction at CMR. All patients with a diagnostic EMB showed late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) in the right ventricle, the right atrium or in the left atrium. The relative importance of different variables predicting outcomes is presented in Figure 1. The top six included four distinct CMR features and two circulating biomarkers (NT-proBNP and high-sensitive troponin T). LGE in the right ventricle and the presence of left ventricular hypertrophy were stronger predictors compared to the remaining variables. The GBM model performed significantly better than the logistic regression model (AUC GBM 0.98, AUC logistic regression 0.93, DeLong’s test p&lt;0.001) (Figure 2).

Conclusion
Using a ML algorithm, CMR LGE, left ventricular hypertrophy, and elevated cardiac biomarkers, stand out as strong overall predictors of an endomyocardial biopsy with a high diagnostic yield.Figure 1Figure 2
Disparity in receiving destination treatment for heart failure patients according to HIV status
Authors: Shoar S , Kumar V , Demelash S , Cascoperez A , Mujahid Z , Hassen G , Patarroyo-Aponte G , Sharma S K , Asadi S 
Published: October 2024

Abstract

Background
Patients living with HIV (PLWH) are well known to be at higher risk of developing cardiovascular diseases. However, PLWH with end-stage HF (ESHF) might not be considered for definitive treatments equally as their HIV-negative counterparts.

Methods
National Inpatient Sample (NIS) database was queried to identify ESHF patients hospitalized to receive left ventricular assist device (LVAD) or undergo heart transplantation (HTX). In-hospital outcomes of this population were stratified based on HIV status.

Results
Weighted data of a total of 16,700 ESHF patients was retrieved, out of which 65 patients (0.2%) had a positive HIV status. Out of 65 PLWH with ESHF, 35 patients (53.8%) received LVAD, and 30 patients (46.1%) received HTX, which were comparable to their HIV-negative counterparts (58.4% and 43.1%, respectively). Although PLWH had a longer length of stay (39.7±35.6 days vs. 49.5±, 42.3 days, p=0.3) and higher hospital charges ($1,458,527±$ 1,509,873 vs. $1,113,344±$953,830) than HIV negative counterparts, the difference was not statistically significant. Mortality rate did not differ between HF patients based on HIV positive status or the bridge/destination treatment they had received.

Conclusions
Although the proportion of PLWH with HF who received HTX has decreased over the last few years, the proportion of those who received LVAD has been on a compensatory rise. HIV positive status is not associated with a higher mortality rate but increases the length of stay and hospital charges.
Acute hemodynamic effect of oral ketones in patients with acutely decompensated heart failure and low cardiac output syndrome: a prospective randomized study.
Authors: Sramko M , Benak A , Holek M , Kleissner M , Pazdernik M , Kissimon F , Svirlochova V , Franekova J , Kautzner J , Melenovsky V 
Published: October 2024

Abstract

Background
Preliminary studies showed positive inotropic effect of mild ketosis in patients with heart failure with reduced ejection fraction (HFrEF).

Purpose
To evaluate the acute hemodynamic effect of oral administration of beta-hydroxybutyrate (OHB) in patients with HFrEF and low cardiac output syndrome.

Methods
Patients with acutely decompensated HFrEF treated with inotropic therapy were randomized (1:1) to enteral bolus of OHB (25g of OHB monoester in 65 ml of solution; H.V.M.N Ketone Ester, H.V.M.N, USA) administered three times with 3-hour intervals or to euvolemic placebo. The serum concentration of OHB, biochemical markers, and invasive hemodynamics (Swan-Ganz catheter with continuous thermodilution) were repeatedly measured before and during 24 hours after administration of OHB. The primary endpoint was the maximum change in cardiac index (CI).

Results
The study included 20 patients with decompensated HFrEF (age: 57 ± 8 years; left ventricular ejection fraction: 21 ± 4%; non-ischemic cardiomyopathy: 16 [80%], median INTERMACS class: 3 [IQR 2 - 4]), who were treated with milrinone (0.5 ± 0.1 ug/kg/min, n=18) or levosimendan (0.1 ug/kg/min up to 25 mg, n=2). Patients in the OHB group (n = 10) did not differ from the placebo group (n = 10) in baseline clinical, biochemical, hemodynamic or echocardiographic characteristics. Baseline OHB concentration was normal (&lt;0.6 mmol/L) in all patients. Administration of OHB increased serum concentration from 0.3 ± 0.2 mmol/L to a maximum of 2.4 ± 0.7 mmol/L (&lt;0.001). Concentrations of OHB peaked at 1.5 ± 0.5 hours after administration of each OHB drink, and the maximum concentration was achieved at 4.1 ± 2.5 hours (Figure 1). No changes in OHB concentration were observed in the placebo group. In both study groups, there was a significant increase of CI at 3 hours compared to baseline, but the increase was significantly greater in the OHB group (OHB: 3.2 ± 0.6 vs. 2.1 ± 0.4 L/min/m2; placebo: 2.3 ± 0.4 vs. 2.0 ± 0.3 L/min/m2; both p&lt;0.001 compared to baseline; p &lt; 0.001 for OHB vs. placebo at 3 hours). The maximum relative increase of CI was 60 ± 24% in the OHB group (p &lt;0.001) and 18 ± 8% in the placebo group (p&lt; 0.01). The change of CI correlated with the change of OHB concentration in the OHB group (r = 0.58, p&lt;0.001) but not in the placebo group (r = 0.1, p = 0.3). The changes in CI were not related to heart rate or concentration of norepinephrine, which did not change significantly throughout the study in both groups.

Conclusion
Oral administration of OHB leads to a significant temporary increase in myocardial contractility. This novel therapeutic concept might be a promising adjunction to inotropic support in patients with decompensated HFrEF.
Comparing treatment strategies for heart failure: a real-world analysis of adding ARNI or SGLT2i to older GDMT
Authors: Amornritvanich P , Numthavaj P , Anothaisintawee T , Tansawet A , Thakkinstian A 
Published: October 2024

Abstract

Background
Heart failure (HF) is a global burden with limited treatment options beyond established guideline-directed medical therapy (GDMT). Newer medications, like angiotensin receptor-neprilysin inhibitors (ARNIs) and sodium-glucose cotransporter-2 inhibitors (SGLT2i), show promise, but real-world evidence on their effectiveness compared to traditional GDMT is lacking.

Objective
This study assessed the real-world effectiveness of adding ARNIs and SGLT2i to existing GDMT regimens for various HF types using network meta-analysis (NMA).

Methods
We analyzed data from observational studies, evaluating the impact of different treatment combinations on all-cause mortality (ACM) and heart failure hospitalization (HFH).

Results
Adding ARNIs to GDMT significantly reduced ACM compared to older regimens (hazard ratio [HR] 0.59, 95% confidence interval [CI] 0.42-0.84), representing a 41% decrease in mortality risk. SGLT2i+2GDMT demonstrated the most significant HFH reduction (HR 0.16, 95% CI 0.06-0.47), translating to an 84% reduction in hospitalization risk.

Conclusion
Incorporating ARNIs or SGLT2i into existing GDMT regimens improves real-world outcomes for HF patients, supporting current guideline recommendations. Personalized treatment plans considering individual needs and preferences are crucial for optimal patient care.Network map of All-cause mortalityRelative treatment effects for ACM
Effect of renin-angiotensin system inhibitors in elderly patients with heart failure and reduced ejection fraction
Authors: Tamaki Y , Yaku H , Yamamoto E , Ozasa N , Inuzuka Y , Enomoto S , Miyake M , Kondo H , Tamura T , Morimoto T , Nakagawa Y , Kato T , Kimura T 
Published: October 2024

Abstract

Background
More than half of the patients admitted for acute decompensated heart failure (ADHF) in Japan are over 80 years of age. Both Japanese and European heart failure guidelines recommend the use of renin-angiotensin system inhibitors (RASIs) in patients with heart failure with reduced ejection fraction (HFrEF). However, there is a paucity of data on the effect of RASIs in elderly patients with HFrEF, because elderly patients have been excluded from large clinical trials.

Purpose
The purpose of the current study was to clarify the effect of RASIs in elderly patients with HFrEF.

Methods
This was a post-hoc analysis of a prospective, observational, multicentre cohort study that enrolled consecutive patients admitted with ADHF to 19 secondary and tertiary hospitals in Japan between October 2014 and March 2016. Patients who were ≥ 80 years old, with left ventricular ejection fraction (LVEF) &lt; 40% and discharged alive were included in the present study. RASIs were defined as either ACE inhibitors or angiotensin II receptor blockers. The primary endpoint was a composite of all-cause death and heart failure (HF) hospitalisation.

Results
Among 518 patients enrolled, 288 patients received RASIs at discharge and 230 patients did not. The median follow-up period was 335 days (interquartile range; 124 – 499 days). Patients receiving RASIs were younger (85.7 ± 4.4 vs. 86.5 ± 4.4 years of age, p=0.03), had a higher body mass index (BMI; 21.4 ± 3.3 vs. 20.6 ± 3.7 kg/m², p=0.01) and better renal function (eGFR; 45.4 ± 21.5 vs. 38.2 ± 19.2 ml/min/1.73m², p&lt;0.001). Patients receiving RASIs had a higher LVEF (30.9 ± 6.3 vs. 28.5 ± 7.1%, p&lt;0.001). The use of beta-blockers at discharge was more prevalent in patients receiving RASIs (77.8% vs. 60.4%, p&lt;0.001), but the use of mineralocorticoid receptor antagonists was not (50.0% vs. 42.2%, p=0.08). The cumulative incidence of all-cause death or HF hospitalisation one year after discharge was significantly lower in patients receiving RASIs (40.1% vs. 59.5%, p&lt;0.001). Even after adjusting for confounders, the risk of a composite of all-cause death and HF hospitalisation was significantly lower in patients receiving RASIs (adjusted hazard ratio 0.59, 95% confidence interval 0.45-0.77, p&lt;0.001). There was no interaction between the effect of RASIs and subgroup factors such as age, BMI, dementia, malignancy, frailty, and renal function.

Conclusion
Use of RASIs at discharge was associated with lower incidence of all-cause death or HF hospitalisation in elderly patients with HFrEF.
Paracetamol and adverse cardiovascular outcomes in patients with heart failure
Authors: Ren Q W , Zhang J N , Guo R A N , Gu W L , Yiu K H 
Published: October 2024

Abstract

Background
Paracetamol is the most widely used pain killer worldwide, yet its potential influence on cardiovascular events among patients with heart failure (HF) remains unclear. Thus, this study aims to investigate both the short-term and long-term effects of paracetamol use on all-cause mortality and cardiovascular events in HF patients.

Methods
Using the previously validated territory-wide clinical information registry, paracetamol use was identified among all eligible patients with HF (N = 211,409) from 2000 to 2020. A case-crossover design was used to investigate the associations between short-term use of paracetamols and all-cause mortality and cardiovascular outcomes. Defined daily dose (DDD) was used to evaluate the dose-response relationship. Additionally, the marginal structural design was applied to model paracetamol use as a time-varying exposure and evaluate its long-term effects during the follow-up period.

Results
Of all eligible subjects, the mean age was 73.2±12.3 years, and 43.6% was male. Over a median follow-up of 10.5 years (interquartile range: 5.7-15.8), 113,258 (53.6%) patients were re-hospitalised for HF, HF-related death occurred in 11,892 (5.6%) patients, incident myocardial infarction (MI) in 28223 (13.3%) patients, incident stroke in 26458 (12.5%) patients, cardiovascular death (CVD) in 72,175 (34.1%) patients and all-cause death in 123,505 (58.4%) patients. Associating HF rehospitalisation to previous paracetamol exposure using the case-crossover design displayed an elevated risk (OR 3.62, 95% CI 3.53-3.71). Associations were similar for MI (OR 5.77, 95% CI 5.50-6.05), stroke (OR 2.37, 95% CI 2.25-2.49), HF-related death (OR 1.86, 95% CI 1.75-1.98), CVD (OR 3.64, 95% CI 3.55-3.73), and all-cause mortality (OR 3.32, 95% CI 3.26-3.39). Moreover, compared with paracetamol users taking the reference dose, users of low, medium and high doses of paracetamol had 16%, 17% and 52% higher risk of HF rehospitalisation. During the long-term follow-up, the average weighted hazard ratio (HR) for HF rehospitalisation in paracetamol users was 2.48 (95% CI 2.46–2.50) as compared with paracetamol non-users after accounting for all-cause mortality as a competing risk. Similarly, the average weighted HR for incident MI or stroke was 2.71 (2.62-2.81) and 3.45 (3.34-3.57), respectively. However, neutral results were shown for HF-related death, CVD and all-cause mortality.

Conclusion
The use of paracetamol among patients with HF is common. Paracetamol was associated with adverse cardiovascular outcomes both in short-term and long-term follow-up with a dose-response relationship, while its impact on long-term mortality remained neutral. Future randomized controlled trials or experimental studies are warranted to gain a comprehensive understanding of the underlying mechanisms driving such associations between paracetamol and adverse cardiovascular outcomes.
The impact of a cardio-geriatric integrated care on mortality and readmissions in older patients with Heart Failure. Results of a quasi-experimental study
Authors: Mazzarone T , Mazzarone T , Okoye C , Pescatore G , Maccioni L , Bianco M G , Guarino D , Giusti A , Guerrini C , Cargiolli C , Virdis A 
Published: October 2024

Abstract

Background
Despite advancements in heart failure (HF) management, older adults still experience adverse outcomes. Post-discharge care for frail elders is often complicated by non-cardiac events and Hospital-Acquired Deconditioning Syndrome. While an integrated multidisciplinary approach combining cardiological and geriatric expertise appears highly beneficial, it remains underutilized.

Purpose
To evaluate the effectiveness of an integrated Cardio-Geriatric approach in improving one-year mortality, reducing HF readmissions and increasing days-alive-out-of-hospital (DAOH) among older patients discharged from acute care hospitals.

Methods
The study utilized a before-and-after design. The study enrolled two groups of patients: the first consisted of individuals aged ≥ 65 years hospitalized for acute HF between January 2018 and December 2019, receiving usual care (UC) post-discharge follow-up (referral to a cardiologist and general practitioner); the second group evaluated outpatients in the Cardio-Geriatric ambulatory clinic (CG) within three weeks after discharge for acute HF between January 2020 and December 2022. Primary outcomes included one-year all-cause mortality, HF readmissions and DOAH. Cox Regression analysis adjusted for age, sex, frailty status, and main comorbidities assessed CG effectiveness.

Results
Among 606 patients (mean age 86 years, 56% females), 477 received US, the remaining 175 were referred to the CG. At 1-year follow-up we observed a significant reduction in re-hospitalizations between CG and UC (36.5% vs. 53.6%; respectively, p &lt; 0.001) and mortality (20% vs. 44.8%; respectively, p &lt; 0.001). CG patients had more than double DAOH (300 ± 100 vs 156 ± 145 days, p &lt;0.001). Cox regression analysis confirmed CG integrated approach as a protective factor for mortality or re-hospitalization even after adjustment for confounders [aHR 0.50; 95% CI (0.28-0.89)]. Respiratory diseases, neurological conditions, and infections were common causes of readmission, emphasizing the need for comprehensive post-discharge care.

Conclusion
The Cardio-Geriatric integrated approach significantly improved outcomes, highlighting the potential of integrated care in addressing the multifaceted needs of older adults with heart failure