bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of inflammation and comorbidities in the association of heart failure with incident cancer in the HUNT3 cohort
Authors: Bertero E , Carmisciano L , Jonasson C , Maack C , Ameri P 
Published: October 2021

Abstract

Background
Conflicting data exist regarding the risk of cancer in patients with heart failure (HF). It was first reported that incident cancer is more common among patients with than without HF, whereas more recent studies indicate that this association is primarily driven by comorbidities. HF, cancer, and comorbidities, such as chronic kidney disease (CKD) and chronic obstructive pulmonary disease (COPD), share numerous risk factors, including a state of chronic low-grade inflammation reflected by elevated circulating levels of pro-inflammatory cytokines. The objective of this analysis was to assess whether chronic low-grade inflammation, as measured by levels of high-sensitivity C-reactive protein (hsCRP), and comorbidities mediate the association of HF with incident cancer.

Methods
We used data from the 3rd wave of the Nord-Trøndelag Health Study (HUNT3), a population-based study that enrolled 50,803 individuals ≥18-year-old between October 2006 and June 2008 in the Nord-Trøndelag County (Norway), from the Cancer Registry of Norway and from the administrative health care records of the same region. Associations between baseline characteristics and the development of cancer were assessed using Cox proportional hazards regression models, using time from HUNT3 enrollment as the time scale. Analyses were performed using R statistical software, version 4.0.2.

Results
In HUNT3, hsCRP was measured in 47,571 individuals at the time of enrollment. Of these, we excluded 2,308 patients because of missing information, leaving a cohort of 45,263 subjects. Figure 1 shows the characteristics of the study population at baseline stratified by hsCRP tertiles. The prevalence of cardiovascular disease, comorbidities, and obesity was progressively higher with increasing concentrations of hsCRP.
During a median follow-up of 12 years, there were 66/408 cases of incident cancer in patients with HF at baseline and 5,024/47,163 in subjects without HF, with a more than 2-fold (HR 2.30; 95% CI 1.80–2.93; p&lt;0.001) increase in risk of developing cancer. After adjusting for age and sex, the excess risk decreased to 43% (HR 1.43; 95% CI 1.12–1.82). When including hsCRP in the model, the HF-related risk of cancer was 33% (HR 1.33; CI 1.04–1.70; p=0.022). Furthermore, when body mass index, CKD, COPD, and smoking and drinking habits were included in the model, the risk of cancer in HF patients compared to individuals without HF was no longer significant (HR 1.23; 95% CI 0.94–1.60; p=0.127). Age, male sex, hsCRP, COPD, obesity, and smoking habits were all associated with an increased risk of cancer (Figure 2).

Conclusions
The increased risk of cancer in HF patients compared with the general population is at least in part explained by concomitant inflammation and comorbidities.

Funding Acknowledgement
Type of funding sources: None. Figure 1Figure 2
Cardiac rest and stress metabolism in type 2 diabetes (T2D): can the diabetic heart flex under stress?
Authors: Athithan L , Parke K.S , Ladwiniec A.H , Adlam D , Gulsin G.S , Marsh A.M , Sian M , McCann G.P , Levelt E 
Published: October 2021

Abstract

Background
Efficient matching of energy supply to demand is essential for maintaining normal cardiac function. Altered cardiac metabolism may contribute to the development of cardiac dysfunction by impairing metabolic flexibility in type 2 diabetes (T2D).

Purpose
We aimed to evaluate the effect of T2D on myocardial substrate preferences in response to acute increases in cardiac workload and the effects on contractile function utilising simultaneous coronary sinus (CS) and aorta blood sampling and cardiac magnetic resonance (CMR) imaging

Methods
Eligible participants without obstructive coronary artery disease (&gt;50% luminal coronary artery stenosis on coronary angiography) underwent transmyocardial arteriovenous blood sampling. Metabolites in paired coronary sinus and arterial samples were quantified to determine myocardial fuel selection at rest and during a stress protocol with intravenous dobutamine. Free fatty acid (FFA), glucose, 3-hydroxybutyric acid (3HBA) and lactate utilisation at rest and haemodynamic stress was calculated as an extraction fraction % (EF). Participants underwent dobutamine stress multiparametric CMR imaging at 3.0 Tesla (Skyra, Siemens, Germany) on a separate visit within 21 days to quantify cardiac volumes, function and perfusion.

Results
Two thousand and sixty-one participants were screened and due to stringent inclusion and exclusion criteria for this mechanistic study, three T2D patients and five matching controls were enrolled. Baseline demographics and metabolic and CMR results are documented in Table 1. At peak stress levels there was a significant increase in FFA use from rest to stress in controls only (p=0.002). There were no significant differences in FA or glucose uptake between T2D patients and controls at rest or stress. 3HBA EF was significantly increased in T2D during stress (25.04% vs 5.31%, p=0.007). Mean FFA and 3-HBA changes calculated as extraction fraction at stress and rest are illustrated in Figure 1.

Conclusions
We demonstrate for the first time in vivo that the diabetic heart switches to ketone bodies during increased workloads as a significant fuel source. At present, it is unknown whether enhanced ketone body metabolism in T2D is beneficial, maladaptive, or a bystander. As the energetic properties of ketones are favourable, increased myocardial ketone oxidation could be an adaptive change designed to compensate for defects in myocardial energy metabolism in diabetes. Further, larger studies are warranted.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): British Heart Foundation - Clinical Research Training FellowshipWellcome Trust Seed Grant Table 1Figure 1
The efficacy of using a holistic 4-domain approach in evaluating frailty in ambulatory patient with heart failure
Authors: Sze S , Pellicori P , Zhang J , Weston J , Squire I B , Clark A L 
Published: October 2021

Abstract

Background
Recently, the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) proposed a four-domain approach to assess frailty in patients with heart failure (HF), to tailor treatment and potentially improve outcomes. The efficacy of such approach in detecting frailty and predicting outcome in patients with HF is unknown.

Aim
To study the prevalence and prognostic value of four different types of frailty deficits: clinical, physical, cognitive and social frailty in ambulatory patients with HF.

Methods
We assessed prospectively consecutive patients attending a routine follow-up visit. Patients with ≥5 non-HF comorbidities were classified as having a clinical deficit. Those who scored ≥3 using the Fried criteria were classified as having a physical deficit. Those who failed to complete a clock test accurately were classified as having a cognitive deficit. Those who lived alone or in a residential home were classified as having a social deficit. All patients were followed for a minimum of 1 year. The primary end point is all-cause mortality.

Results
We enrolled 467 patients (67% male, median (25th–75th centile) age 76 (69–82) years, median (25th–75th centile) NT-proBNP 1156 (469–2463) ng/L). 65% of patients had clinical deficits, 52% had a physical deficit, 39% had a social deficit and 18% had a cognitive deficit. 28% had 2, 19% had 3, 8% of patients had all 4 deficits; 16% had none. An increasing number of frailty deficits was associated with worse symptoms, higher NT-proBNP and less likelihood of being prescribed guideline-indicated HF treatment.
During a median follow-up of 554 days, 82 patients died. The presence of any frailty deficit was associated with increased risk of mortality. (Figure 1) The more frailty deficit a patient had, the higher the risk of mortality (Figure 2). A base model (including age, body mass index, NYHA class and log [NT-proBNP]) for predicting mortality at 1 year achieved a C-statistic of 0.78. Addition of all four deficits improved the performance of the base model (C-statistic = 0.82).

Conclusion
Clinical, physical, cognitive and social deficits are common in patients with HF and are associated with a poor outcome. Future studies should evaluate how a domain-based approach can be used to optimise care for frail patients with HF.

Funding Acknowledgement
Type of funding sources: None. Figure 1Figure 2
Influence of diabetes, heart failure, and NT-proBNP on cardiovascular outcomes in patients with atrial fibrillation – insights from a cohort study of 7,412 patients with extended follow-up
Authors: Hofer F , Pailer U , Sulzgruber P , Gerges C , Winter M P , Giugliano R P , Gottsauner-Wolf M , Huelsmann M , Kazem N , Koller L , Schoenbauer R , Niessner A , Hengstenberg C , Zelniker T A 
Published: October 2021

Abstract

Background
Diabetes and heart failure (HF) promote atrial fibrillation (AF) and are associated with an increased risk of adverse cardiovascular (CV) events in patients with AF. Because of effective anticoagulation options, AF patients are now more likely to develop HF than a stroke or a systemic embolic event. Appropriate risk stratification of patients with AF should therefore not only consider the risk for stroke but also for HF events.

Methods
Patients with AF admitted to a tertiary academic center between 01/2005 and 07/2019 were identified through a search of electronic health records. The primary outcome of interest was CV death or hospitalization for HF (HHF). We used Cox regression models adjusted for age, sex, estimated glomerular filtration rate, diabetes, HF, body mass index, prior myocardial infarction, hypertension, smoking, C-reactive protein, and LDL-C. To select the most informative variables and overcome the limitations of stepwise regression procedures, we performed a least absolute shrinkage and selection operator logistic regression in a model that incorporated diabetes, HF, NT-proBNP, and the covariates for adjustment in combination with 10-fold cross-validation.

Results
In total, 7,412 patients (median age 70 years, 39.7% female) were included in the present analysis and followed over a median of 4.6 years. Both diabetes (Adjusted (Adj.) hazard ratio (HR) 1.87, 95% confidence interval (CI) 1.55 to 2.25) and HF (Adj. HR 2.57, 95% CI 2.22 to 2.98) were significantly associated with CV death/HHF after multivariable adjustment. Compared to patients with diabetes, HF patients had a higher risk of HHF but a similar risk of CV and all-cause death. There was a robust relationship between CV death/HHF and NT-proBNP (Adj. HR for 1-unit increase in standardized log-transformed biomarker 1.86, 95% CI 1.67 to 2.07). NT-proBNP showed good discriminatory performance (AUC 0.78, 95% CI 0.77–0.80), and the addition of NT-proBNP to the covariates used for adjustment resulted in a significant AUC improvement (Δ=0.04, P&lt;0.001). With least absolute shrinkage and selection operator logistic regression, the strongest associations for CV death/HHF were obtained for NT-proBNP (OR 2.69 per 1-SD in log-transformed biomarker), HF (OR 1.73), and diabetes (OR 1.65).

Conclusion
These findings suggest that the influence of diabetes and HF expand beyond the risk of stroke and systemic embolic events to CV death/HHF in an unselected AF patient population. NT-proBNP may provide improved risk assessment in AF patients.

Funding Acknowledgement
Type of funding sources: None. Figure 1. Forest Plot
Similar incidence of over and underdiagnosis of heart failure in hospitalized patients with type 2 diabetes mellitus
Authors: Medovchshikov V , Yeshniyazov N , Khasanova E , Kobalava Z 
Published: October 2021

Abstract

Purpose
To assess the incidence of over and underdiagnosis of heart failure (HF) in hospital patients with type 2 diabetes mellitus (T2DM)

Methods
In the single-center prospective study (registry) from 01.08.2018 to 31.01.2019 we included 1008 patients admitted to the city hospital. Key inclusion criteria: a history of T2DM, age ≥40 years. Key exclusion criteria: any other disorders of carbohydrate metabolism, age &lt;40 years, acute coronary syndrome, functionally dependent patients. We assessed the presence of HF in the diagnosis at admission by the following criteria: the presence of HF stage C or D (ACCF/AHA) and at least II NYHA functional class. All patients underwent standard echocardiography and NT-proBNP assessment at 1–3 days after admission. The diagnosis of HF was established by the 2016 ESC HF Guidelines. After the examination, the patients were divided into subgroups: “Confirmed HF” (HF was in the diagnosis, its presence was confirmed), “Unconfirmed HF” (HF was in the diagnosis, its presence was excluded), “First diagnosed HF” (HF was not in the diagnosis, its presence was confirmed) and “Absent of HF” (HF was not in the diagnosis and its presence was excluded). We also analyzed the reasons for admissions in all patients.

Results
The presence of HF in the diagnosis at admission was in 68.8% (n=693) of patients and, accordingly, it was absent in 31.2% (n=315). By the ESC HF Guidelines HF was diagnosed in 68.1% (n=686) and, accordingly, in 31.9% (n=322) it was excluded. The analysis results by the diagnosis at admission are presented in Fig. 1. The analysis of the reasons for admission depending on the HF status is presented in Fig. 2. In 35 patients admitted with HF decompensation the presence of HF was not confirmed and the diagnosis was revised: atrial fibrillation in 11 (31,4%) patients, exacerbation of COPD – 7 (20,0%), pulmonary embolism – 6 (17,1%), pneumonia – 4 (11,4%), kidney diseases – 4 (11,4%), and asthma – 3 (8,7%).

Conclusion
Among hospitalized patients with T2DM, there is a similar incidence of over and underdiagnosis of HF. Patients with first diagnosed HF were more likely to be admitted for reasons unrelated to cardiovascular diseases (CVD), most often with hyperglycemia (Fig. 2). Patients with unconfirmed HF – for reasons related to CVD, while the reason for admission in a quarter of patients was HF decompensation (Fig. 2). Despite the availability of examination for HF, the problem of its diagnosis is still relevant.

Funding Acknowledgement
Type of funding sources: None. Figure 1Figure 2
Prognostic value of simple risk index and plasma volume status in patients with acute decompensated heart failure
Authors: Yamada T , Watanabe T , Morita T , Kawasaki M , Kikuchi A , Kawai T , Seo M , Nakmura J , Kayama K , Fukunami M 
Published: October 2021

Abstract

Background
Increased heart rate (HR) and low systolic blood pressure (SBP) are associated with adverse clinical outcomes in patients admitted for acute decompensated heart failure (ADHF), and simple risk index (SRI) based on easily assessed clinical characteristics (age, HR, and SBP) provides prognostic information. On the other hand, plasma volume (PV) expansion plays an essential role in heart failure, and PV status is has been reported to be associated with adverse outcomes in ADHF patients. However, there is no information available on the value of the combination of SRI and PV status in patients admitted for ADHF.

Methods and results
We studied 301 patients admitted for ADHF. At the admission, SRI was calculated as (HR x [age/10]2)/SBP. PV status was calculated as the following: Actual PV = (1 − hematocrit) x [a + (b x body weight)] (a=1530 in males and a=864 in females, b=41 in males and b=47.9 in females), Ideal PV = c x body weight (c=39 in males and c=40 in females), and PV status = [(actual PV − ideal PV)/ideal PV] x 100(%). During a follow-up period of 4.3±3.2 yrs, 95 patients had all-cause death (ACD) and 68 patients had cardiovascular death (CVD). At multivariate Cox analysis, SRI and PV status were significantly associated with ACD and CVD, independently of the prior history of heart failure hospitalization and serum creatinine and sodium levels, after the adjustment with serum albumin level and anemia. Patients with both greater SRI (≥35.1 by ROC analysis; AUC 0.599 [0.524–0.674]) and greater PV status (≥8.1% by ROC analysis; AUC 0.625 [0.550–0.700]) had a significantly higher risk of ACD and CVD than those with either or none of them (ACD: 49% vs 27% vs 24%, p&lt;0.0001, CVD: 39% vs 18% vs 15%, p&lt;0.0001,respectively).

Conclusion
The combination of SRI and PV status might be useful for stratifying patients at risk for the total mortality and cardiovascular death in patients with ADHF.

Funding Acknowledgement
Type of funding sources: None.
Long-term prognostic value of the combination of malnutrition and fib-4 index in patients admitted with acute decompensated heart failure
Authors: Yamada T , Watanabe T , Morita T , Kawasaki M , Kikuchi A , Kawai T , Seo M , Nakamura J , Kayama K , Fukunami M 
Published: October 2021

Abstract

Background
Malnutrition is associated with increased mortality risk in patients with acute decompensated heart failure (ADHF). Cardiohepatic interactions have been a focus of attention among heart failure. It was reported that liver stiffness assessed by non-invasive fibrosis marker such as Fibrosis-4 (FIB4) index provide prognostic information in ADHF patients. However, there is no information available on the long-term prognostic value of the combination of malnutrition and FIB4 index in patients admitted for ADHF.

Methods and results
We studied 294 patients admitted for ADHF, who were discharged with survival. Nutritional status was evaluated by Geriatric Nutritional Risk Index (GNRI) calculated as follows: 14.89 × serum albumin (g/dl) + 41.7 × BMI/22, and malnutrition was defined as GNRI &lt;92. FIB4 index was calculated by the formula: age (yrs) × AST[U/L] / (platelets [103/μL] × (ALT[U/L])1/2), and abnormal FIB4 index was defined as &gt;2.67. During a mean follow-up period of 4.3±3.3 yrs, 94 patients had all-cause death. At multivariate Cox regression analysis, GNRI and FIB4 index were significantly associated with the total mortality, independently of prior heart failure hospitalization, systolic blood pressure, and serum creatinine level. Patients with malnutrition and abnormal FIB4 index had a significantly higher risk of the total mortality than those with either and none of them (49% vs 32% vs 20%, p&lt;0.0001, respectively).

Conclusions
The combination of malnutrition and FIB4 index might be useful for stratifying ADHF patients at higher risk for the total mortality.

Funding Acknowledgement
Type of funding sources: None.
Safety of endomyocardial biopsy in new-onset acute heart failure requiring veno-arterial extracorporeal membrane oxygenation
Authors: Van Der Boon R M A , Den Dekker W K , Meuwese C L , Lorusso R , Von Der Thusen J H , Constantinescu A C , Manintveld O C , Delnoij T S R , Van Der Heijden J J , Van Mieghem N M D A , Den Uil C A 
Published: October 2021

Abstract

Background
Refractory cardiogenic shock (CS) complicating new onset acute heart failure (new-AHF) is a medical emergency, requiring immediate mechanical circulatory support (MCS) to prevent hemodynamic deterioration. When non-invasive testing is impossible, endomyocardial biopsy (EMB) has an important role in determining the etiology of new-AHF.

Purpose
The aim of this study was to determine the procedural safety of EMB in patients with new-AHF requiring VA-ECMO. Additionally, we describe the detection rate of an underlying etiology of new-AHF on histopathological examination.

Methods
A retrospective, multicenter cohort of patients undergoing EMB while requiring VA-ECMO for new-AHF between 1990 and 2020 was compared with a cohort of non-transplant related biopsies not requiring VA-ECMO. Primary endpoint of the study was the safety of EMB with a secondary endpoint being the detection rate of an underlying etiology causing new-AHF on histopathologic examination.

Results
A total of 23 patients underwent EMB while requiring VA-ECMO (10.0%), 125 (54.3%) during an unplanned admission and 82 (35.7%) in elective setting. Major complications occurred in 8.3% of all procedures with a significantly higher rate in patients requiring VA-ECMO (26.1% vs. 8.0% vs. 3.7%,p=0.003), predominately due to occurrence of sustained ventricular tachycardia or need of resuscitation (13.0% vs. 3.2% vs. 1.2%,p=0.02). EMB led to a histopathological diagnosis in 78.3% of the patients requiring VA-ECMO which consisted primarily of patients with myocarditis (73.9%).

Conclusions
EMB in patients requiring VA-ECMO can be performed albeit with a substantial risk of major complications. This risk of the procedure was offset by a high detection rate of an underlying etiology on histopathological examination. The important therapeutic and prognostic implications of EMB in this population warrant further refinement to improve procedural safety.

Funding Acknowledgement
Type of funding sources: None. Major safety endpoints according to EMB
Efficacy and feasibility of heart failure nurses to deliver a lungs and inferior vena cava ultrasound assessment (LUICA) protocol and prediction of outcomes
Authors: Zisis G , Yang Y , Whitmore K , Lay M , Huynh Q , Neil C , Carrington M , Marwick T H 
Published: October 2021

Abstract

Background/Introduction
Congestion is the main cause for hospital admission and readmission in heart failure (HF), with almost half being discharged with symptoms that suggest residual congestion. Novel non-invasive assessments (eg. lung ultrasound; [LUS], and Inferior Vena Cava [IVC]) may be used to assess congestion. A LUs and IvC Assessment (LUICA) delivered by HF nurses before discharge, could detect residual congestion, optimise diuresis and guide post discharge treatment.

Purpose
To determine the ability of HF nurses to successfully learn a LUICA protocol, obtain interpretable images, provide diagnostic reports and predict outcomes.

Methods
A teaching program focused on quantification of congestion by counting B-lines and reporting estimated right atrial pressure (e-RAP) from IVC congestion. LUICA readings were dichotomised based on lung congestion (≥10 vs &lt;10 B-lines), the presence of lung pathology (consolidation, atelectasis, effusion) and IVC congestion (e-RAP &gt;3mmHg vs 3mmHg). LUICA (8 lung zones + 2 IVC zones) was added to pre-discharge review (4 days post-admission) by HF nurses in 108 hospitalised pts (72±13 years; 58% male) with acute HF, fluid overload, and a variety of lung pathology. Images were assessed for quality (good, usable, measurable or not measurable) and interpreted by a LUICA expert and HF nurses, blinded to admission diagnosis. The predictive value of LUICA readings for patient outcomes (readmission or mortality) was expressed as risk ratio.

Results
The quality at the majority of the images was assessed as good or usable (expert: 82/107, nurses: 66/107, p=0.02). Readmission was predicted by both experts and nurses (picture 1).

Conclusions
HF nurses can be adequately trained in a 10 Zone LUICA and successfully obtain interpretable images. The predictive power of their interpretation is similar to experts.

Funding Acknowledgement
Type of funding sources: Other. Main funding source(s): The University of MelbourneBaker Heart & Diabetes Institute Readmission risk ratio based on LUICA