bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of novel cardiac biomarkers in diagnosis of decompensated heart failure
Authors: Froehling T , Mirna M , Paar V , Shomanova Z , Van Almsick V , J Motloch L , Semo D , Makowski L , Rukosujew A , Sindermann J R , Reinecke H , Lichtenauer M , Pistulli R 
Published: October 2022

Abstract

Aims
Heart failure (HF) remains a major therapeutic and diagnostic challenge. In this study we aimed to analyze the predictive potential of four novel cardiovascular biomarkers – soluble urokinase-type plasminogen activator receptor (suPAR), vascular cell adhesion molecule (CAM-1), heart-type fatty acid binding Protein (H-FABP) and growth/differentiation factor 15 (GDF-15) in detecting cardiac decompensation in patients with HF.

Methods
In total, 136 patients (40 decompensated HF, 96 compesated HF) were retrospectively enrolled and the serum biomarker concentrations of GDF-15, suPAR, H-FABP and CAM-1 were analyzed by Enzyme Linked Immunosorbent Assay (ELISA). Biomarker concentrations were correlated with clinical and biochemical parameters of enrolled patients, the predictive value for detecting cardiac decompensation was assessed by ROC-plots, as well as univariate and multivariate logistic regression analysis. Cut-offs for cardiac decompensation were calculated by means of the Youden index.

Results
A significant increase in the levels of suPAR (1.6-fold change, p&lt;0.0001), CAM-1 (1.6-fold change, p&lt;0.0001), HFABP (2.2-fold change, p=0.0458) and GDF-15 (1.7-fold change, p=0.0009) was detected in all patients with decompensated HF compared to patients with compensated HF. In univariate logistic regression analysis, plasma concentrations of GDF-15, H-FABP, suPAR and CAM-1 were significantly associated with the risk for cardiac decompensation. For GDF-15, suPAR and CAM-1, this association remained significant even after correction for confounders in a multivariate logistic regression analysis. Additionally, AUCs (GDF-15: 0.759, 95% (0.683–0.866), suPAR: 0.838, 95% (0.750–0.926), CAM-1: 0.838, 95% (0.750–0.926)) and optimal cut-offs (GDF-15: 1404.8835 pg/ml, suPAR: 4774.027 pg/ml, CAM-1: 4.74027 ng/ml) of the biomarkers were calculated. Correlation analyses found clinical and biochemical parameters such as creatinine as well as inflammatory marker CRP to be significantly correlated with novel biomarkers (r&gt;0.3, p&lt;0.001. In conjunction with the results for the AUC of NTproBNP (AUC=0.785), suPAR (AUC=0.838) and CAM-1 (AUC=0.838 more accurately prediced cardiac decompensation in heart failure than NTproBNP (Figure 1).

Conclusion
In conclusion, the investigated novel cardiovascular biomarkers could be a valuable tool to facilitate therapeutic decisions in patients with HF and suspicion of cardiac decompensation. Parameters such as renal function should be taken into account.

Funding Acknowledgement
Type of funding sources: None.
Exercise MR-proANP unmasks latent right heart failure in CTEPH
Authors: Kriechbaum S D , Birmes J , Wiedenroth C B , Gruen D , Vietheer J , Richter M J , Guth S , Roller F , Liebetrau C , Hamm C W , Keller T , Rieth A 
Published: October 2022

Abstract

Background
Chronic right heart failure is the major determinant of outcome in chronic thromboembolic pulmonary hypertension (CTEPH). Thus, its early detection is crucial for optimal patient management. Hemodynamic assessment with invasive right heart catheterization and the measurement of natriuretic peptides at rest are established diagnostic tools in this context. An elevated right atrial pressure (RAP) is a sensitive parameter of right right heart failure. Mid-regional pro-atrial natriuretic peptide (MR-proANP) is a natriuretic peptide that reflects right atrial stress levels.
There is a growing recognition of exercise diagnostics in the assessment of right heart failure, particularly in patients with normal or borderline findings at rest. There are no data on the dynamics of MR-proANP in correlation to RAP during physical exercise.

Purpose
The present study was designed to investigate the dynamics of RAP and MR-proANP during physical exercise in patients with CTEPH and to determine whether these parameters might serve as a tool to measure exercise-dependent atrial stress as an indicator of right heart failure.

Methods
This observational cohort study included 100 CTEPH patients who underwent right heart catheterization during physical exercise (eRHC). Blood samples for MR-proANP measurement were taken prior, during, and after eRHC. MR-proANP levels were correlated to RAP levels at rest, at peak exercise (eRAP), and during recovery. RAP at rest ≤7 mmHg was defined as normal and eRAP &gt;15 mmHg as suggestive of right heart failure.

Results
During eRHC mean RAP increased from 6±4 mmHg to 16±7 mmHg (p&lt;0.001). MR-proANP levels and dynamics correlated with RAP at rest (rs=0.61; p&lt;0.001; figure 1a) and at peak exercise (rs=0.66; p&lt;0.001; Figure 1b). Furthermore, the relative percent increase in MR-proANP correlated with the relative percent increase in eRAP (rs=0.52; p&lt;0.001; Figure 1c) Logistic regression analysis revealed the peak MR-proANP level (B=0.058; p=0.004) and the right atrial area (B=0.389; p&lt;0.001) to be associated with eRAP dynamics. A peak MR-proANP level ≥139 pmol/L (AUC=0.81) and recovery level ≥159 pmol/L (AUC=0.82) predicted an eRAP &gt;15 mmHg. Physical exercise unmasked RH failure in 39% of patients with normal RAP at rest; they were also characterized by a more distinct increase in MR-proANP levels (p=0.005) and higher peak (p&lt;0.001) and recovery levels (p&lt;0.001).

Conclusions
RAP and MR-proANP dynamics unmask manifest and latent right heart failure in CTEPH patients, which may be useful in estimating prognosis.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): SFB 1213 area CP-01 projectWilliam G. Kerckhoff-FoundationKerckhoff Heart Research Institute (KHFI)German Center for Cardiovascular Research (DZHK)
Heart failure is associated with low circulating levels of secreted frizzled receptor protein 5 (Sfrp5)
Authors: Kelly C , Chu M , Untaru R , Assadi-Khansari B , Chen D , Croft A , Horowitz J , Sverdlov A L , Ngo D T M 
Published: October 2022

Abstract

Background/Introduction
Obesity and metabolic dysregulation are closely associated with the pathophysiology of multiple cardiovascular diseases (CVD). To date, the pathophysiological mechanism(s) of obesity and its link with cardiovascular systems remain largely unknown. Adipose tissue inflammation as a result of excessive fat expansion in obesity, leading to increased systemic production of growth factors and recruitment of inflammatory cells have been postulated to be a major factor. Secreted frizzled-related protein 5 (SFRP5) is an anti-inflammatory adipokine that is linked with obesity and metabolic regulation and has been indicated to affect cardiovascular functions. Currently, the role of circulating SFRP5 levels as a biomarker for cardiovascular diseases are poorly understood, with studies yielding discordant results.

Purpose
This study aims to evaluate the relationship between circulating SFRP5 and cardiovascular functions in a cohort of patients with established CVD.

Methods
Patients (n=262, 148 male (56.5%), age (68±11 yrs)) presenting to the cardiology unit for cardiovascular investigations were recruited into the study. Plasma SFRP5 levels were measured via enzyme-linked immunosorbent assay (ELISA). Associations between plasma SFRP5 levels, cardiovascular functions, and patients' co-morbidities were analysed using univariate and multivariate analyses.

Results
Plasma SFRP5 levels were significantly lower in patients presenting with: heart failure (HF) vs non-HF (median; (10.7 vs 31.0; p&lt;0.001); coronary artery disease (CAD) vs non-CAD; (11.0 vs 33.8; p&lt;0.001); and atrial fibrillation (AF) vs non-AF; (11.2 vs 23.2; p=0.001). On univariate analyses, SFRP5 levels also significantly positively correlated with left ventricular ejection fraction (LVEF) (r=0.52, p&lt;0.001), estimated glomerular filtration rate (eGFR) (r=0.16, p=0.02), total cholesterol levels and triglycerides (r=0.29, p&lt;0.001; r=0.17, p&lt;0.01 respectively). Low SFRP5 levels were correlated with high C-reactive protein (CRP) and E/E' (r=−0.29, p&lt;0.001, r=−0.30, p&lt;0.001, respectively). Patients with HF, CAD, statin use, low LVEF, low triglycerides, high CRP and high eGFR were associated with lower SFRP5 levels independent of age, BMI or diabetes on multivariate analysis (overall model r=0.729, SE=0.638).

Conclusion
Our results show that low plasma SFRP5 levels are independently associated with HF, CAD, and impaired systolic and diastolic functions. These results suggest that SFRP5 may regulate cardiovascular functions independent of obesity and metabolic regulations.

Funding Acknowledgement
Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Heart Foundation of Australia Future Leader FellowshipsNSW Ministry of Health EMC FellowshipHeart Foundation of Australia Future Leader Fellowship
MR-proADM is a strong independent predictor of long-term all-cause mortality risk in patients with chronic heart failure: results from the E-INH study
Authors: Kerwagen F , Sahiti F , Sehner S , Albert J , Cejka V , Moser N , Morbach C , Gueder G , Frantz S , Ertl G , Angermann C E , Stoerk S 
Published: October 2022

Abstract

Background
Mid-regional proadrenomedullin (MR-proADM) is a blood biomarker indicating critical illness. Its short-term prognostic relevance has been investigated in several conditions including heart failure (HF). Yet, the long-term prognostic utility is unknown.

Methods
We conducted a post-hoc analysis of the Extended Interdisciplinary Network for Heart Failure (E-INH) study, which investigated the long-term effects of a HF nurse-led remote patient care program (HeartNetCare-HFTM [HNC]). Patients from nine regional centers in Germany hospitalized with HF and a left ventricular ejection fraction (LVEF) &lt;40% were randomized into HNC vs. Usual Care. MR-proADM and other standard biomarkers for disease progression and systemic inflammation were measured from venous blood collected at study inclusion, i.e. during index hospitalization. The prognostic utility was assessed using Kaplan-Meier plots and Cox proportional hazard models, and compared with other biomarkers by ROC curves.

Results
From 919 out of the 1022 recruited patients (90%), baseline levels of MR-proADM were available: median MR-proADM 0.89 (quartiles 0.63, 1.28) nmol/l; mean age 68±12 years; 28% women; 45% in class III or IV of the New York Heart Association (NYHA) classification.
Median LVEF was 31 (25, 37) %. Median levels of NT-proBNP, high sensitive C-reactive protein (hsCRP), tumor necrosis factor (TNF)-a, and interleukin-6 (IL-6) were 3045 (1087, 7759) pg/ml, 9.2 (3.3, 25.2) mg/l, 13.4 (10.4, 17.5) pg/ml, and 4.9 (2.0, 11.4) pg/ml, respectively. Higher levels of MR-proADM at baseline were associated with age, female sex, NYHA class, NT-proBNP, hsCRP, IL-6, and TNF-α, while there was an inverse association with LVEF.
In the course of 10 years of follow-up, 691 (68%) patients died. Unadjusted MR-proADM strongly predicted all-cause death when used as a continuous variable (HR 1.31 per nmol/l, 95% CI 1.26–1.37; p&lt;0.001) or when grouped into quartiles (HR 1.85, 95% CI 1.71–2.0; p&lt;0.001). Adjustments for age, sex and NYHA functional class did not materially alter the strong association. Plotting quartiles of MR-proADM in a Kaplan-Meier curve (see Figure 1) confirmed this findings. As shown in Figure 2, MR-proADM had the highest area under the curve (AUC) in ROC analysis when compared to other biomarkers.

Conclusion
MR-proADM appears to be a strong and independent predictor for long-term all-cause mortality risk in HF with reduced ejection fraction (HFrEF). Therefore, assessing MR-proADM may contribute to better categorization of risk and tailored care. Its clinical utility needs to be investigated in future studies.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): BMBF
Dynamic changes of left atrial function during supine ergometry: evidence for interplay with left ventricular function and dynamic changes of pulmonary pressure
Authors: Armenis I , Ritsatos K , Gonteva M , Kyrzopoulos S , Tsiapras D , Athanassopoulos G 
Published: October 2022

Abstract

Introduction
Despite the pivotal role of left atrial (LA) function in a variety of cardiac pathologies, it has been studied mainly at rest.

Aim
Aim of the study was to assess the effect of semisupine exercise ergometry (Ex) on LA function, by volumetric and strain parameters and to interrogate relationships with left ventricular (LV) function and noninvasive hemodynamics.

Patients and methods
Eighty-two patients (female 26, age: mean/SD 61/15) referred for Ex were studied. The following parameters were estimated by 2 D echo: LV systolic (LVvolsyst) and diastolic (LVvoldiast) volume, ejection fraction (LVEF), stroke volume (LVsv), LA minimum (LAvolmin) and maximal volume (LAvolmax), LA emptying fraction [LAEF), LA reservoir volume (LAvolres = LAvolmax − LAvolmin), LA reservoir fraction (LAresFR = LAvolres/LVsv), LA conduit volume (LAcondvol = LVsv − LAvolres) and LA conduit fraction (LAcondFR = LAcondvol/LVsv). LV strain (LVSR) and LA strain (LASR) were estimated by 2D analysis. Peak tricuspid gradient (TRpg) was also estimated. Parameters were measured at rest R and Ex and the respective % changes (%d) were calculated.

Results
SBE performance was efficient with a % achieved target heart rate 73/9 and workload Watts 96/21. Systolic blood pressure increased from 139/53 to 179/31. Parameters with significant change during Ex are in the table (all p&lt;0.001).
LVSRr and LVEFr were both related inversely with LAvolresR (r=−0.39/p=0.001 and r=−0.24/p=0.05) and LAresFRr (r=−0.34/p=0.001 and r=−0.25/p=0.04). LVEFr was related inversely with LAcondRFr r=−0.24/p=0.04). LVSR was related inversely with LAvolresEx (r=−0.43/p=0.001). LVSREx was related inversely with LAvolresR (r=−0.24/p=0.04) and LAcondRFr (r=−0.25/p=0.04).
The %dLVSR was related inversely with LAEFr (r=−0.25/p=0.04). The %dLVEF was related inversely with LAresFREx (r=−0.27/p=0.03) and LAcondRFr (r=−0.27/p=0.03).
The % increase in TRpg during SBE was positively related with LAresFREx r=0.30/p=0.04 and inversely with LAcondFREx (r=−0.30/p=0.04) (Figure 1).

Conclusion
SBE induces LA dynamic changes in a spectrum of volumetric and strain indices. Dynamic changes of LV are related with reservoir and conduit LA function. LA reservoir and conduit function during SBE are related with the induced dynamic changes of pulmonary pressure, thus further supporting the clinical relevance of the respective evaluation.

Funding Acknowledgement
Type of funding sources: None.
Haemodynamic forces as predictors of cardiac remodelling and outcome in heart failure with reduced ejection fraction treated with sacubitril/valsartan
Authors: Fabiani I , Pugliese N R , Castiglione V , Pedrizzetti G , Tonti G , Chubuchny V , Becherini F , Taddei C , Gimelli A , Del Punta L , Balletti A , Masi S , Cameli M , Emdin M , Giannoni A 
Published: October 2022

Abstract

Background
Angiotensin receptor-neprilysin inhibitor (ARNI) is a cornerstone of treatment in heart failure (HF) with reduced ejection fraction (HFrEF), but its effectiveness shows interindividual differences.

Objectives
To evaluate the predictive value of echo-derived hemodynamic forces (HDF), together with other echocardiographic, biohumoral and cardiopulmonary parameters on a) response to ARNI after 6 months; b) adverse cardiovascular events at follow-up.

Methods
Eighty-nine consecutive HFrEF patients from two HF centers performed clinical evaluation, laboratory analyses, rest echocardiography and cardiopulmonary exercise testing. Response to ARNI at 6 months was considered in patients without HF admissions, death, or urgent heart transplant and with a ≥50% reduction in NT-proBNP levels and/or ≥10% increase in left ventricle ejection fraction. After 6 months, patients were followed up for a composite endpoint of cardiovascular death, HF-related hospitalization and new-onset atrial fibrillation.

Results
Response to ARNI was documented in 45/89 (51%) of patients. At baseline, responders and non-responders were paired in clinical assessment, conventional echocardiography, functional status and therapy. At multivariate logistic regression analysis, HDF-derived whole cardiac cycle left ventricle strength (wLVS) was the only independent predictor of ARNI response at 6 months (odds ratio 1.36, 95% confidence interval 1.10–1.67; p=0.004). A wLVS ≥3.7% showed a good accuracy in predicting ARNI response (AUC = 0.736, 0.607–0.840; p&lt;0.0001). During a median of 33 (IQR 23–41) months, wLVS increase from baseline to 6-month (ΔwLVS) showed a high discrimination ability at time-dependent ROC analysis (optimal cut-off: ≤0.5%; AUC=0.811, 0.69–0.90; p&lt;0.0001), stratified prognosis at Kaplan-Meier analysis (log-rank p&lt;0.0001), and remained an independent prognostic predictor of the composite endpoint (hazard ratio 0.76, 0.61–0.95; p&lt;0.01) even after adjusting for clinical, functional and conventional echocardiographic parameters.

Conclusions
HDF analysis may help predict ARNI response and optimize follow-up and medical/device strategies in patients with HfrEF.

Funding Acknowledgement
Type of funding sources: Public hospital(s). Main funding source(s): Fondazione Toscana Gabriele Monasterio, Pisa, Italy
Histological validation of cardiac 99mTc-DPD uptake in patients with cardiac transthyretin amyloidosis
Authors: Ungericht M , Groaz V , Messner M , Zaruba M M , Lener D , Stocker E , Kroiss A , Poelzl G 
Published: October 2022

Abstract

Background
Cardiac transthyretin (ATTR) amyloidosis is a progressive and fatal disease caused by the extracellular deposition of misfolded ATTR protein in the myocardium. In an era where new therapies are rapidly emerging, development of non-invasive imaging modalities to quantify amyloid burden over time is of utmost importance. Although endomyocardial biopsy (EMB) remains the gold standard in amyloid detection and typing, 99mTc-DPD scintigraphy is a widely available and accurate tool for non-invasive diagnosis of cardiac ATTR amyloidosis. However, it remains to be determined whether the degree of cardiac 99mTc-DPD uptake correlates with the histological amyloid infiltration on EMB – thus, justifying 99mTc-DPD scintigraphy as a disease monitoring tool.

Aim
This single-centre observational study aimed to compare the extent of histologic amyloid burden on EMB with the quantification of cardiac 99mTc-DPD uptake on scintigraphic planar images and SPECT/CT acquisitions in cardiac ATTR amyloidosis.

Methods
26 patients with cardiac ATTR amyloidosis were enrolled. Patients were included in case of (1) EMB-proven ATTR amyloidosis and (2) availability of 99mTc-DPD scintigraphy (reference activity: 550 MBq). Visual interpretation using the Perugini score, quantitative analysis of cardiac 99mTc-DPD uptake by planar whole-body imaging and SPECT/CT using regions of interest (ROI) were performed, and heart to whole-body ratio (H/WB) was measured. Histological amyloid load was quantified as percentage of the analysed myocardial tissue using Sulfated Alcyan Blue staining and the Fiji-ImageJ programme. Pearson's and Spearman's correlation were used for correlation analysis and assessment of agreement.

Results
ATTR patients had a median age of 77 [73–79] years and were predominantly male (85%). An abnormal Perugini score (i.e. 2 or 3) was present in 25 patients (96%), whereas 1 patient was assigned Perugini score 1 (4%). Increased cardiac tracer uptake was documented in all patients, both on 99mTc-DPD planar scintigraphy (ROImean 129±37) and SPECT/CT (ROImean 369±142). Histologic amyloid burden on EMB was 32±19% on average. It significantly correlated with Perugini score (r=0.56 p=0.003), as well as with cardiac 99mTc-DPD uptake (planar: r=0.54 p=0.006, SPECT/CT: r=0.48 p=0.018) and H/WB (r=0.41 p=0.046).

Conclusion
We have demonstrated a good correlation between histological amyloid infiltration on EMB and cardiac 99mTc-DPD uptake on scintigraphic planar images and SPECT/CT scans, illustrating the potential of 99mTc-DPD scintigraphy to yield reliable quantitative information on cardiac amyloid burden. Further investigations with a larger number of patients are needed to confirm our findings and to implement thresholds in cardiac 99mTc-DPD uptake for being used for guiding disease and therapy management.

Funding Acknowledgement
Type of funding sources: None.
Association of cardiothoracic ratio with heart failure hospitalization in patients with atrial fibrillation: the Fushimi AF Registry
Authors: Ikeda S , Iguchi M , Ogawa H , Minami K , Ishigami K , Doi K , Hamatani Y , Yoshizawa T , Ide Y , Fujino A , Ishii M , Masunaga N , Wada H , Abe M , Akao M 
Published: October 2022

Abstract

Background
Chest radiography is the most common diagnostic imaging test in clinical medicine, and the cardiothoracic ratio (CTR) is a readily available and non-invasive tool with which to assess the volume status and cardiomegaly. However, it remains unknown whether CTR on chest radiography is associated with the incidence of HF hospitalization in AF patients remains unclear.

Methods
The Fushimi AF Registry is a community-based prospective survey of AF patients in Fushimi-ku, Kyoto, Japan. The inclusion criterion of the registry is the documentation of AF at 12-lead electrocardiogram or Holter monitoring at any time, and there are no exclusion criteria. We started to enroll patients from March 2011, and follow-up data were available for 4,489 patients by the end of August 2021. In the present study, 3,727 patients with available data of CTR were examined. We divided the patients into two groups according to their CTR at baseline; Higher group (CTR ≥50.0%, n=2,696) and Lower group (CTR &lt;50.0%, n=1,031), and compared the clinical background and outcomes between the two groups.

Results
The proportion of female was grater in Higher group, and the patients in Higher group were older. The patients in Higher group had higher prevalence of HF, hypertension and chronic kidney disease. During the median follow-up of 3,033 days, in Kaplan-Meier analysis, the incidence rates of HF hospitalization were higher in Higher group (Higher group: 2.5% per person-year vs. Lower group: 1.1%; p&lt;0.01). Multivariate Cox proportional hazards regression analysis revealed that higher CTR (≥50.0%) was an independent determinant of the incidence of HF hospitalization. Furthermore, when we divided the patients into four groups based on the quartile of CTR; Q1 (CTR&lt;49.0%), Q2 (49.0≤CTR&lt;53.8%), Q3 (53.8≤CTR&lt;59.0%), Q4 (59.0%≤CTR), the incidence of HF hospitalization was more frequent in patients with higher CTR, regardless of the presence or absence of prior hospitalization for HF (Figure).

Conclusion
In Japanese AF patients, patients with higher CTR had significantly higher incidence of HF hospitalization, regardless of the prevalence of prior hospitalization for HF.

Funding Acknowledgement
Type of funding sources: None.