bluuebunny/crossref_metadata_2025_split huggingface dataset:
The added value of cardiopulmonary exercise testing in the diagnosis of heart failure with preserved ejection fraction
Authors: Massa L , Baratto C , Perego G B , Losito M , Bursi F , Parati G , Guazzi M , Caravita S 
Published: October 2024

Abstract

Background
Diagnosing heart failure with preserved ejection fraction (HFpEF) is challenging. Two validated algorithms, the HFA-PEFF and H2FPEF scores, have been proposed to guide our clinical practice. Many patients are categorized into an intermediate probability for HFpEF, representing a diagnostic "gray zone." This necessitates further evaluation, including right heart catheterization (RHC) at rest and possibly during exercise, to confirm or exclude the diagnosis. RHC, while informative, is resource-consuming and requires execution in specialized centers. Cardiopulmonary exercise testing (CPET) may offer a non-invasive and cost-effective alternative for differential dyspnea diagnosis.

Purpose
To evaluate the role of CPET in the diagnostic algorithm of unexplained dyspnea/suspected HFpEF.

Methods
This single-center retrospective study analyzed patients with a left ventricular ejection fraction (LVEF) ≥ 50% who underwent CPET for unexplained dyspnea from 2016 to 2020. We assessed HFpEF probability using the H2FPEF score and the HFA-PEFF algorithm. We hypothesized that specific CPET parameters (VO2 peak&lt; 80% of predicted and/or VE/VCO2 slope &gt; 35) might provide complementary information to the HFpEF probability scores. Additionally, we hypothesized that CPET could help identifying HFpEF in patients with intermediate probability in a subcohort of patients who underwent exercise RHC.

Results
Out of 103 patients, 61 (59%) were categorized as intermediate probability of HFpEF according to the HFA-PEFF score, and 59 (57%) according to the H2FPEF score. CPET results (VO2 peak and VE/VCO2 slope) were not associated with the pre-test probability of HFpEF as defined by either of the two scores. Exercise RHC was performed in 26 (43%) and in 27 (46%) patients with intermediate HFA-PEFF score and intermediate H2FPEF score, respectively. Among these patients with intermediate HFpEF probability, VO2 peak &lt; 80% and/or VE/VCO2 slope &gt; 35 had a good specificity and positive predictive value for HFpEF, as compared with exercise RHC (Table).

Conclusions
CPET provides complementary information to HFA-PEFF and H2FPEF scores. In particular, our results suggest that CPET may reclassify as HFpEF over 25% of patients with an intermediate HFpEF probability according to either the HFA-PEFF score or the H2FPEF score, potentially obviating the need for RHC. Thus, CPET might be incorporated into the HFpEF diagnostic algorithms.Table
The diagnostic value of endomyocardial biopsy in the era of precision medicine: data from over 8,000 patients with comprehensive biopsy diagnostics
Authors: Escher F , Baumeier C , Aleshcheva G , Gross U , Schultheiss H P 
Published: October 2024

Abstract

Background
Endomyocardial biopsy (EMB) is an important diagnostic tool for evaluating various cardiac diseases such as myocarditis and storage disorders as well as for the monitoring heart transplant patients. Despite advances in non-invasive imaging techniques to characterize myocardial tissue, EMB remains the gold standard for definitive diagnosis and initiation of specific therapy. Here we report EMB laboratory results from over 8,000 patients and demonstrate the diagnostic utility of EMB.

Methods and results
We retrospectively reviewed EMB analyses performed at our institution. EMBs for monitoring graft rejection were not included in this study. Clinical data, suspected clinical diagnoses and EMB-based laboratory results were collected. Histopathological, immunohistochemical and molecular biology biopsy findings were recorded and reviewed for degree of concordance with clinical diagnosis. In total, EMBs from N=8,085 consecutive patients with unexplained heart failure were analyzed. The comprehensive EMB analysis revealed that N=616 (7.6%) patients had cardiac storage disease, most of whom had cardiac amyloidosis (N=606). N=357 (4.4%) patients were diagnosed with acute forms of myocarditis, including N=95 cases with active myocarditis, N=148 cases with giant cell myocarditis, N=95 cases with sarcoidosis and N=19 cases with eosinophilic myocarditis. A total of N=3,392 (42%) patients were found to have inflammatory heart disease such as inflammatory cardiomyopathy and borderline myocarditis, whereby a differentiation of the inflammatory infiltrates revealed considerable differences in the quality of inflammation. Viral genomes were found in the myocardium of N=6,072 (75%) patients, with treatment-relevant viral infections detected in N=2,015 (25%) cases. The remaining N=1,705 (21%) patients were diagnosed with other cardiomyopathies, including dilated cardiomyopathy (N=1,252), heart failure with preserved ejection fraction (N=325), hypertrophic cardiomyopathy (N=117) and arrhythmogenic right ventricular cardiomyopathy (N=11).

Conclusions
This retrospective study of over 8,000 patients with heart failure clearly shows that a definitive diagnosis is only possible with a comprehensive EMB diagnosis and leads to specific therapy in 79% of the cases. In the remaining 21% of patients, infectious and inflammatory causes could be excluded in order to initiate standard heart failure therapy. It is important to emphasize here that the quality of the inflammation and therapy-relevant viral infections cannot be detected with imaging techniques, which underlines the clinical-therapeutic importance of endomyocardial biopsy.
Exploring heart failure prevalence and overlooked dimensions: a comprehensive NT Pro-BNP study in high-risk primary care patients
Authors: Celik A , Yesil E , Kilic U , Akcay Ozyurt G , Aytimur S , Demir M , Eker H N , Col A S , Ergen M , Bozkaya S , Okyay I S , Yirtar M , Korkmaz D , Kirdag A , Ozcan I T 
Published: October 2024

Abstract

Background
Heart failure (HF) is a prevalent syndrome linked to significant morbidity and mortality, especially in those with comorbid conditions like diabetes, hypertension, and atherosclerotic cardiovascular disease. Early detection and intervention are crucial. Natriuretic peptides, particularly NT-proBNP, are promising biomarkers for identifying at-risk individuals, but their use in primary care settings is not fully understood.

Methods
This prospective cohort study enrolled 874 participants aged 40 and above with documented risk factors for HF, such as diabetes mellitus, hypertension, metabolic syndrome, obesity, atherosclerotic cardiovascular disease, genetic variants for cardiomyopathy, or exposure to cardiotoxic agents. NT-proBNP levels were measured in blood samples collected at primary care clinics, and participants underwent comprehensive cardiac evaluations at a referral hospital. Clinical characteristics, laboratory findings, electrocardiography, and echocardiography results were recorded.

Results
The study included 874 patients with at least one risk factor for HF, with a mean age of 62.5 ± 9.1 years and 51.9% female. According to the 2022 AHA/ACC/HFSA HF Guideline, 69.1% were Stage A HF, 21.9% Stage B HF, and 9% Stage C HF. Clinical characteristics, laboratory and echocardiographic findings are shown in Picture 1. The majority had hypertension (71.1%), while other prevalent comorbidities included diabetes mellitus (43.4%), dyslipidemia (35.2%), obesity (27.1%), and atherosclerotic cardiovascular disease (26.2%). Laboratory findings showed a significant decrease in HbA1C, eGFR, LDL, triglycerides, and hemoglobin from Stage A to C HF. Median NT-proBNP levels rose from Stage A to C HF (46.4 pg/mL in Stage A, 219 pg/mL in Stage B, and 268.5 pg/mL in stage C), with 84.8% of Stage B HF patients exhibiting elevated levels. NT-proBNP levels were correlated positively with left atrial volume index, left ventricular mass index, age, E/e’, and estimated systolic pulmonary artery pressure levels. Conversely, NT-proBNP levels showed a negative correlation with estimated glomerular filtration rate and left ventricular ejection fraction. Among Stage C patients, 92.4% had HFpEF. The Picture 2 depicted the study's design and outcomes, providing a comprehensive visual representation.

Conclusion
NT-proBNP screening in primary care settings identified a substantial proportion of individuals with undiagnosed HF, particularly those in Stage B and Stage C. The high prevalence of HFpEF underscores the need for comprehensive evaluation and management strategies targeting this population. Early detection facilitated by NT-proBNP screening may lead to timely interventions and improved outcomes in individuals at risk for HF.
Serum transferrin concentration: a new prognostic biomarker in heart failure with reduced ejection fraction
Authors: Zinoune L , Bouchlarhem A , Bazid Z , Ismaili N , El Ouafi N 
Published: October 2024

Abstract

Introduction
Iron deficiency (ID) is a common comorbidity in patients with reduced heart failure (HFrEF), and is associated with poor clinical status and outcomes, but there is not enough data investigating serum transferrin concentration (STC) as a biomarker HFrEF to predict prognosis and mortality.

Purpose
We investigated relationship between STC at admission and all-cause mortality during follow-up in HFrEF.

Methods
We reviewed the medical data of 420 patients hospitalised in our institution for HFrEF over a period of 18 months. Laboratory tests were performed on the first 24 hours of admission. Patients were divided into two groups according to STC, using the value of 199 μg/dl as the cut-off. This value was determined from the ROC analysis to be the value with the highest sensitivity and specificity. Then we analysed relationship between STC at admission and all-cause mortality during follow-up between the two groups, after adjustment of the various variables described in the literature.

Results
Of 420 patients with HFrEF, 18.6% had STC ≤ 199 μg/dl (group 1) and 81.4% had STC &gt; 199 μg/dl (group 2) with no difference in age and sex distribution (p = 0.873 ; p = 0.304). Patients with low STC were more likely to be diabetic (70.5% vs 46.5% ; p &lt; 0.001), have dyslipidemia (52.6% vs 33%; p = 0.002), and history of chronic renal failure (6.4% vs 2.0% ; p = 0.045). There was no relation between STC and NYHA class (p = 0.776), hospital stay (p = 0.491) nor EF (p = 0.146). Biologically, lower STC was significantly associated with higher serum ferritin (292.77 vs 198.17 ; p &lt; 0.001), TSAT (68.30 vs 22.21 ; p = 0.020) and C-reactive protein (CRP) (124.91 vs 39.98 ; p = &lt; 0.001), lower plasma B-type natriuretic peptide (BNP) (5798.32 vs 6449.97 ; p = 0.002), with no difference in haemoglobin level (p = 0.272) and estimated glomerular filtration rate (eGFR) (p = 0.260). The prevalence of iron deficiency by the ESC criteria was lower in those with low STC; ferritin &lt; 100 μg/l (15.4% vs 29.2% ; p = 0.015) or TSAT &lt; 20% (33.3% vs 51,8% ; p = 0.004). There was no difference between the two groups in term of NYHA class and EF at three months (p = 0.87, p = 0.108). However, all-cause mortality during follow-up was significantly associated with low STC (37.2% vs 17.0% ; p &lt;0.001). (Figure 1)
In multivariable analysis, all-cause mortality was independently associated with STC ≤ 199 μg/dl (HR 1.71; 95% CI : 1.08 ; 2.7 ; p = 0.02). This is the same finding for the ischaemic origin of HFrEF (HR 2.1 ; p = 0.001), therapeutic inertia during follow-up (HR 5.53 ; p &lt;0.001) and EF &lt; 36% (HR 1.03 ; p = 0.047) (Figure 2).

Conclusion
More data are required before the routine use of STC as a biomarker of prognosis in HFrEF, but it may represent a reliable and cost-effective option to predict mortality.FIGURE 1FIGURE 2
Circulating secretoneurin concentrations predict cardiovascular death in ambulatory patients with heart failure
Authors: Sze S , Squire I B , Omland T , Rosjo H 
Published: October 2024

Abstract

Background
Secretoneurin (SN) is a novel biomarker, which predicts cardiovascular (CV)-related mortality in patients with acute dyspnea and sepsis. Higher SN concentrations have also been found associated with all-cause death in outpatients with heart failure (HF), but whether SN primarily reflects cardiovascular (CV)-related mortality in HF outpatients is not known.

Objectives
To evaluate the relation between SN concentrations and CV- & non-CV death in ambulatory patients with HF.

Methods
We studied 184 consecutive patients who attended our HF clinic for routine follow up and had stored blood samples available for SN analysis. SN concentrations were measured with a CE-marked SN ELISA assay. We assessed the associations between SN concentrations and CV & non-CV death. Mortality was ascertained using medical records, autopsy reports and death certificates, and CV deaths included sudden cardiac deaths or mortality due to myocardial infarction, HF or stroke. We assessed association with CV & non-CV death by Kaplan-Meier curves and by Cox proportional hazard regression analysis.

Results
Median age was 76 years (range: 38-94 years) and two thirds were male. Sixty-three percent had HF with reduced ejection fraction, 22% had NYHA III/IV symptoms and median NT-proBNP was 1079 (interquartile range: 462-2347) ng/L. Median SN level was 60 (range: 21-134) pmol/L.
In multivariable linear regression analysis, impaired renal function and lower body-mass index were significantly associated with increasing (log)SN concentration.
During median follow up of 540 days, there were 18 CV deaths, including 15 HF deaths, and 7 non-CV deaths. A higher SN concentration was associated with higher risk of CV death, while we did not find statistically significant association between SN concentrations and non-CV deaths (Figure). Patients with SN concentration in the top tertile had 15-fold increased risk of CV death compared to patients with SN concentration in the lowest tertile. In multivariable Cox regression analysis that adjusted for age, NYHA functional class, frailty status, increasing SN concentrations were independently associated with CV death: hazard ratio per logSN (95% CI): 3.01 (1.02-8.90), p=0.04.

Conclusion
In ambulatory patients with HF, circulating SN concentrations were predictive of CV death. Higher SN concentrations in ambulatory HF patients seemed to be linked to impaired renal function and lower body-mass index.
Figure: Kaplan Meier curves illustrating the relation between SN tertiles and (A) CV mortality (B) Non-CV mortality.
Association of soluble ST2 with heart failure and other comorbidities in patients with severe coronary heart disease
Authors: Pec J , Tafelmeier M , Schmid C H , Maier L , Arzt M , Wagner S 
Published: October 2024

Abstract

Background
Circulating levels of soluble suppression of tumorigenicity-2 (sST2) reflect vascular congestion, inflammation, and fibrosis. sST2 has been proposed as a useful biomarker to predict the mortality and hospitalization due to heart failure. However, there is limited evidence regarding the relationship between sST2 and heart failure, as well as other comorbidities, in severe coronary heart disease (CAD).

Purpose
This study aims to measure the circulating levels of soluble ST2 (sST2) in a large population of patients with severe CAD to determine its association with heart failure, cardiac function, inflammation, and other important comorbidities.

Methods
This subanalysis is part of the ongoing perspective observational study. Available serum samples from 520 patients undergoing elective coronary artery bypass grafting (CABG) were analysed for sST2 levels. The inclusion criteria were written informed consent and age between 18-85 years. Exclusion criteria for this analysis were severe valvular disease, severe chronic obstructive pulmonary disease, oxygen therapy, nocturnal positive airway pressure support or mechanical ventilation, and the need for catecholamines or circulatory assist devices.
The circulating levels of human sST2 were measured from frozen serum (-80°C) using commercially available ELISA kits. The plasma was diluted 100 times to detect sST2 levels (assay range of 31.2 - 2,000 pg/mL). Two measurements were taken to account as means for intra-assay variabilities. Logarithmic transformation was used to convert non-normal distributed data. Student t' test and linear regression were applied to categorical or continuous variables as appropriate.

Results
sST2 levels (median 20.4 ng/ml, [IQR 15.5 – 28.8]) significantly predict worse left ventricular ejection fraction (β = -0.164, p = 0.006), and significantly correlate with levels of NT-proBNP (β = 3.263, p &lt; 0.001), hs-Troponin T (β = 3.391, p &lt; 0.001), high-sensitivity C-reactive protein (β = 2.472, p = 0.014) and heart failure (p= 0.002). Interestingly, common comorbidities such as chronic kidney disease (estimated glomerular filtration rate &lt; 60 mL/min/1.73 m2, p = 0.004), diabetes mellitus (p = 0.001) and higher levels of glycated haemoglobin (HbA1c, β = 3.615, p &lt; 0.001) showed also a significant association with sST2 levels. No significant association of sST2 was observed with arterial hypertension (p = 0.190), atrial fibrillation (p = 0.289), obesity (BMI ≥ 30 kg/m2, p = 0.302), sleep apnoea (apnoea-hypopnoea index ≥ 15/h, p = 0.068), peripheral artery disease (p = 0.823), or previous stroke (p = 0.861).

Conclusion(s)
Circulating levels of sST2 significantly correlate with heart failure, NT-proBNP, hs-TnT, and hs-CRP in patients with severe CAD. Additionally, sST2 levels were found to be elevated in patients with diabetes mellitus and chronic kidney disease.
Albuminuria is associated with progression of diastolic dysfunction in patients at risk for cardiovascular disease
Authors: Min K D , Matsumoto Y , Asakura M , Ishihara M 
Published: October 2024

Abstract

Background
The number of the patients with heart failure with preserved ejection fraction (HFpEF) is increasing as society ages, which indicates that the number of pre-HFpEF patients is increasing even more. To combat this sociomedical burden, it is critical to establish cost-effective and simple biomarkers to identify the high-risk population at early phase of the disease. Recent studies demonstrated the association between albuminuria and incident heart failure, but the prognostic impact of albuminuria on diastolic dysfunction, an early phenotype of HFpEF, has not been elucidated.

Purpose
To examine the impact of albuminuria on the diastolic function over time in the patients with cardiovascular risks.

Methods
One hundred and fifty-eight patients with at least one cardiovascular risk factor without history of heart failure were followed up for 5 years. Echocardiogram was conducted at baseline, year 3, and year 5. Diastolic dysfunction was defined as E/e’ &gt;14. Albuminuria was defined as urine albumin-to-creatinine ratio (UACR) 30 ≧mg/gCre. The patients with ejection fraction &lt;40% and those had diastolic dysfunction at baseline were excluded from the study. The relationship between albuminuria at baseline and diastolic function at year 3 and 5 were investigated.

Results
Among 158 subjects, 27 showed albuminuria at baseline and the prevalence of hypertension, dyslipidemia, and diabetes was not significantly different between patients with and without albuminuria. The baseline E/e’ tended to be higher in patients with albuminuria, although the difference was not statistically significant (Fig1: E/e’ = 10.0±2.4 vs. 9.4±2.2, p = 0.08) . However, the patients with albuminuria showed a steeper increase in E/e’ than those without albuminuria, and the significant difference was observed at year 3, that was even greater at year 5 (Fig1: E/e’ = 11.1±2.8 vs 10.0±2.6, p = 0.04 in year 3, E/e’ = 12.5±4.1 vs 10.3±2.9, p = 0.002 in year 5, respectively). Furthermore, log UACR at baseline showed significant correlation with E/e’ at year 5 (p = 0.02, r = 0.21) and normo-, micro-, and macroalbuminuria (UACR&lt;30, 30-300, and &gt;300mg/gCre, respectively) at baseline showed elevated E/e’ at year 5 in this order ( p = 0.01 for UACR&lt;30 vs. 30-300mg/gCre, and p = 0.04 for UACR&lt;30 vs. &gt;300mg/gCre, reapectively ). The prevalence of incident diastolic dysfunction increased greater in patients with albuminuria throughout the follow-up period and the difference reached statistical significance at year 5 (Fig2: 18.5% vs. 9.2%, p = 0.28 for year 3, and 25.9% vs. 8.4%, p = 0.009 for year 5, respectively).

Conclusion
In the patients with cardiovascular risk factors, albuminuria was associated with development and progression of diastolic dysfunction over subsequent 5 years. Future prospective study is warranted to investigate the effectiveness of albuminuria-directed care to prevent development of HFpEF.
Exploring vocal biomarkers as non-invasive fine-tuning assays of cardiovascular health: heart failure model
Authors: Yilmaz M B , Durmus M , Yilmaz R E , Polat Z P , Colakoglu S 
Published: October 2024

Abstract

Background
Mobile health (mHealth) technologies offer a promising avenue for non-invasive heart failure monitoring through vocal biomarkers. The relationship between feature changes in anonymous and standardized voice recordings of heart failure patients and the NYHA scores of the same patients is assessed, aiming to identify vocal biomarkers as delicate indicators of chronic noncommunicable disease progression and/ or fluctuation.

Methods
In a cardiology outpatient setting, 55 chronic heart failure patients provided voice recordings via a mobile app, performing specific vocal tasks prospectively. We analyzed waveforms visually via Mel spectrograms and extracting features by audio processing, focusing on chroma centroids and tonnetz measurements across 147 clinical and laboratory parameters (Mean NYHA: 2.62, SD: 0.56). Applying Ordinary Least Squares (OLS) test, we assessed the relevance of spectral bandwidth mean (0.04), spectral bandwidth std (0.00), spectral roll-off std (0.011) between NYHA scores, given each p-score &lt; 0.05.

Results
147 voice recordings taken from 55 patients were analyzed to examine whether there were any correlations between changes in the voice recordings and NYHA scores. OLS test underscored the significance of spectral bandwidth mean (0.04), spectral bandwidth std (0.00), spectral roll-off std (0.011) between NYHA scores with p-value &lt; 0.05. These findings show the potential role of multiple vocal features in reflecting heart failure progression and/or fluctuation. Analysis based on the clinical status progression from NYHA 2 to NYHA 3 over time showed notable changes in chroma centroids (mean = 0.006, std = 0.174, skew = 0.179, kurtosis = 0.205) and tonnetz (mean = 0.023, std = 0.131, skew = 0.023, kurtosis = 4.247).

Conclusion
This investigation highlights vocal biomarkers' potential in heart failure management, offering insights into non-invasive monitoring techniques and shows the importance of standardised recording procedures and patient engagement for data integrity. Future directions include quantifying vocal changes' correlation with clinical status and integrating additional parameters (e.g., edema, weight) to enhance predictive models for personalised care.Vocal features according to NYHA scores