bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longitudinal characterization of clinically relevant haemodynamics in conscious Ossabaw pigs with HFpEF
Authors: Balitzki J , Bauersachs J , Thum T , Hueser J , Sandner P , Mondritzki T 
Published: October 2022

Abstract

Background
The constantly growing population of patients suffering from heart failure with preserved ejection fraction (HFpEF) is one of the largest unmet needs in cardiovascular medicine and translational animal models are important for identification and profiling of novel therapeutic approaches. Large animal models have shown that chronic cardiac pressure overload by aortic banding (AoB), when combined with a Western diet leads to left ventricular hypertrophy, diastolic dysfunction and metabolic syndrome in the Ossabaw pig, reflecting important features of human HFpEF characteristics. However, the requirement of invasive diagnostics under anaesthesia often limits the ability to monitor disease development continuously and compromises the results. Therefore, current disease models lack the temporal progression of clinically relevant HFpEF parameters like the left ventricular end diastolic pressure (LVEDP) and time constant of left ventricular relaxation (Tau).

Purpose
We aim to non-invasively investigate disease progression in Ossabaw pigs exhibiting a cardiometabolic HFpEF phenotype. The longitudinal assessment of LVEDP, Tau and heart rate (HR) should identify a time window to test novel therapeutics.

Methods
Naive, female Ossabaw pigs were instrumented with telemetric devices followed by AoB to induce chronic cardiac pressure overload. The wound healing and acclimatization period was followed by the start of a Western diet feeding regime to mimic components of the metabolic syndrome. Disease progression was characterized over 9 months by monthly telemetric recordings of LVEDP, Tau and HR and compared to a control (Ctrl) measurement in healthy animals. All animal studies followed the `Principles of laboratory animal care'.

Results
Compared to Ctrl the LVEDP is significantly elevated already 1 month (+8.90±0.4 mmHg) after AoB and further increases over time until 8 months (+18.80±0.4 mmHg) post AoB. Significant elevations in Tau are evident 4 months (+1.61±0.4 ms) post AoB. After 1 month the HR is significantly elevated (+13.90±0.7 bpm) but tends to normalize between 5 to 7 months post AoB. After AoB a maximal relative increase in LVEDP (+5.12±0.4 mmHg), Tau (+5.04±0.4 ms) and HR (+16.90±0.7 bpm) can be observed after 8 months.

Conclusions
We present long term haemodynamic changes over time in a translational in vivo model for HFpEF in Ossabaw pigs with high temporal resolution. For the first time elevations in key parameters allow to set a time point where HFpEF characteristics are evident, and a drug testing regime could be started. The opportunity to non-invasively and longitudinally follow on LVEDP, Tau and HR will be a clear benefit in the development of novel treatment options for HFpEF.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): Bayer AG, Wuppertal
Value of the HFA-PEFF and H2FPEF scores in patients with heart failure and preserved ejection fraction caused by cardiac amyloidosis
Authors: Tomasoni D , Aimo A , Merlo M , Nardi M , Adamo M , Cani D , Lombardi C M , Pancaldi E , Panichella G , Porcari A , Vergaro G , Sinagra G , Rapezzi C , Emdin M , Metra M 
Published: October 2022

Abstract

Aims
The HFA-PEFF and H2FPEF scores have been developed to diagnose heart failure with preserved ejection fraction (HFpEF), and hold prognostic value. Their use in patients with HFpEF caused by cardiac amyloidosis (CA) has never been investigated.

Methods and results
We evaluated the diagnostic and prognostic value of the HFA-PEFF and H2FPEF scores in 304 patients from 3 cohorts with HFpEF caused by transthyretin (ATTR)-CA (n=160, 53%) or immunoglobulin light-chain (AL)-CA (n=144, 47%). A diagnosis of HFpEF was more likely using the HFA-PEFF score with 2 (1%), 71 (23%), and 231 (76%) patients ranked as having a low (0–1), intermediate (2–4) or high (5–6) probability of HFpEF, respectively. Conversely, 36 (12%), 179 (59%) and 89 (29%) of patients ranked as having a low (0–1), intermediate (2–5) or high (6–9) probability of HFpEF using the H2FPEF score. During a median follow-up of 19 months (interquartile range 8–40), 132 (43%) patients died. The HFA-PEFF score, but not the H2FPEF, predicted a high risk of all-cause death which remained significant after adjustment for age, AL-CA diagnosis, high-sensitivity troponin T, N-terminal pro-B-type natriuretic peptide, and echocardiographic parameters, including left ventricular (LV) global longitudinal strain, LV diastolic function and right ventricular function (hazard ratio 1.51, 95% confidence interval 1.16–1.95, p=0.002 for every 1-point increase in HFA-PEFF).

Conclusions
The HFA-PEFF score has a high sensitivity to diagnose HFpEF caused by CA and holds independent prognostic value for all-cause mortality, while the H2FPEF score does not.

Funding Acknowledgement
Type of funding sources: None.
Nitro-oxidative stress impairs single cardiomyocyte adrenergic reserve in a murine model of HFpEF
Authors: Semmler L , Jeising T , Huettemeister J , Schiattarella G G , Oeing C U , Heinzel F R 
Published: October 2022

Abstract

Background
Exercise intolerance is the central symptom of patients with heart failure and preserved ejection fraction (HFpEF). Underlying reduced cardiac functional reserve in response to adrenergic stimuli (stress testing) has been suggested but the molecular mechanisms are insufficiently understood. In cardiomyocytes, nitric oxide (NO) modifies contractility and is required to achieve a full adrenergic response. Recently, dysregulation of NO release has been described to contribute to HFpEF. In a murine model of HFpEF, we investigated cardiomyocyte's adrenergic functional reserve and the role of NO in cardiomyocyte contractility, calcium handling and adrenergic reserve.

Methods
Firstly, the effects of NO on sarcomere shortening and calcium handling (Fura-2) were studied in isolated, adult ventricular cardiomyocytes (AMVMs) from 8–10 weeks old, male C57BL/6J mice. Secondly, male C57BL/6J mice (12w) were fed regular CHOW (Sham) or a high fat diet (D12492, Research Diet) and L-NAME (1g/l, via the drinking water) for 15 weeks to induce HFpEF. At week 27, mice underwent echocardiography and exercise testing (treadmill). In AMVMs isolated from HFpEF and Sham mice, we quantified sarcomere shortening, calcium handling (Fura-2), release of NO (CuFL2) and reactive oxygen species (DCF) before and after the addition of isoproterenol (ISO, 1μM), in the absence and presence (40 min preincubation) of an inhibitor of inducible NO Synthase (1400W) or a denitrosylating agent (glutathione).

Results
In AMVMs, addition of the NO donor SNAP (10μM) increased calcium transient amplitude and accelerated relaxation time. Inhibition of NO synthesis with L-NAME (100μM) impaired adrenergic response upon exposure to ISO. HFpEF mice (evident by diastolic dysfunction (e/e' ratio) and lung edema (wet lung weight / TL)) exhibited significantly reduced exercise capacity (running distance). In AMVMs isolated from HFpEF mice, NO and ROS release were increased at baseline, associated with an increased sarcomere shortening amplitude and faster relaxation and calcium removal as compared to Sham. Strikingly, after the addition of ISO, the adrenergic functional reserve (cellular inotropy and lusitropy) was significantly lower in HFpEF vs. Sham AMVMs. Preincubation with the iNOS inhibitor 1400W or glutathione restored adrenergic inotropic and lusitropic reserve in HFpEF AMVMs.

Conclusion
In HFpEF, adrenergic reserve is impaired on a single cardiomyocyte level. This is at least partially related to an increase in NO release. Pharmacologic inhibition of iNOS improved adrenergic reserve in HFpEF.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): DFG
Type III collagen formation is significantly associated with risk of outcome in HFpEF patients but loses its significant association with underlying AF
Authors: Angeli E , Reese-Petersen A , Gonzalez A , Lopez B , Ravassa S , Genovese F , Karsdal M , Diaz J 
Published: October 2022

Abstract

Introduction
Heart failure with preserved ejection fraction (HFpEF) is the most common type of heart failure, associated with high morbidity and mortality. Atrial fibrillation (AF) has been associated with structural remodelling and fibrosis and can coexist with HFpEF. Type III collagen is the second most abundant collagen in the heart wall and has been associated with cardiac fibrosis. It has been previously shown that type III collagen formation, measured by PRO-C3, is prognostic for all-cause mortality in HFpEF.

Purpose
In this study, we aimed at investigating if the prognostic power of PRO-C3 in relation to all-cause mortality would be affected by underlying AF in HFpEF patients.

Methods
The analysis included 166 individuals with hypertensive HFpEF. The patients were classified in three groups according to NYHA classification, 43.2% in NYHA Class II, 52.5% NYHA Class III and 2.5% NYHA Class IV. A previous history of AF was present in 53.4% of the patients. Cardiac function was assessed by echocardiography and standard clinical measures. Type III collagen formation was evaluated by means of ELISA with the biomarker PRO-C3, which targets the released N-terminal pro-peptide of type III collagen.

Results
Levels of PRO-C3 were significantly elevated in HFpEF patients with AF (p=0.0063). PRO-C3 was significantly predictive of all-cause mortality in HFpEF patients (AUC=0.643, p=0.0053), but lost its significant association when factoring in AF (AUC=0.581, p=0.235). There was an increased risk of all-cause mortality (p=0.0089) but not statistically significant differences in HFpEF patients with AF (p=0.178) with increasing tertiles of PRO-C3.

Conclusions
Type III collagen formation as measured by PRO-C3, was increased in patients with HFpEF and previously diagnosed AF. However, while PRO-C3 can be predictive of all-cause mortality in HFpEF patients, it lacks predicting ability when AF is considered. The presented data suggest a potential role of increased type III collagen formation in HFpEF patients with adverse outcomes, which is consistent with the presence of increased fibrosis, and can potentially be used as a tool of risk stratification.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): Nordic Bioscience A/S
Lung fluid levels estimated by remote dielectric sensingTM values and invasive hemodynamic measurements
Authors: Imamura T , Hori M , Kinugawa K 
Published: October 2022

Abstract

Background
Remote dielectric sensing (ReDSTM) is a recently introduced non-invasive electromagnetic-based technology to quantify lung fluid levels (Figure 1A). The association between ReDS values and invasively measured hemodynamics, particularly among those with small body size, remains uncertain.

Methods
Consecutive patients with chronic heart failure who were admitted to our institute and underwent right heart catheterization as well as simultaneous ReDS measurement at clinically stable conditions between Sep and Nov 2021 were prospectively included. The correlation between ReDS values and PCWP was investigated.

Results
A total of 30 patients (median 79 [73, 84] years old, 13 men) were included. Median ReDS value was 26% (22%, 28%). ReDS values had a moderate correlation with PCWP (r=0.698, p&lt;0.001; Figure 1B), even among those with a height &lt;155 cm. ReDS values with a cutoff 28% predicted a PCWP &gt;15 mmHg with sensitivity 0.70 and specificity 0.75.

Conclusions
A non-invasive electromagnetic-based technology ReDS might be a promising tool to estimate cardiac pressure in patients with heart failure, even among those with smaller body size.

Funding Acknowledgement
Type of funding sources: None.
Phenotyping of heart failure with preserved ejection faction using health electronic records and echocardiography
Authors: Pierre-Jean M , Bouzille G , L'official G , Cuggia M , Donal E 
Published: October 2022

Abstract

Patients suffering from heart failure (HF) symptoms and a preserved left ventricular ejection fraction (HFpEF) present very different clinical phenotypes that could influence their survival. This study aims to identify phenotypes of this type of HF by using the medical information database from our hospital center.

Methods and results
We develop a POC of machine learning model to predict the phenotype of patients suffering from HFpEF from both clinical and echocardiography data from data warehouse of our hospital center. We performed a retrospective observational study. We used the inpatient clinical data warehouse at our hospital center to identify patients suffering from HFpEF and having echocardiography between January 2018 and December 2019. A list of relevant clinical and echocardiographic variables was established by cardiologists. For clinical variables, we extracted information from the data warehouse using either structured data (ICD-10 codes, lab results, ...) or regular expressions for narratives. The echocardiographic parameters consisted only in structured data. We performed a two-step cluster analysis to identify common characteristics among patients. The final sample eligible included 2500 patients with echocardiography and diagnosed for HFpEF. The variables included in the two-step cluster analysis were both clinical (13 variables) and echographic (17 variables). Four clusters were identified from the clustering algorithm. The groups were relatively well balanced with respectively: 753, 744, 519 and 545 patients. After performing survival analysis, we observed that clusters have significative different survival curves in particular for death. The performances of these two models are satisfying with an AUC upper than 0.97 and an accuracy upper than 0.92) (Figure 1).

Conclusion
In the future, this work could be deployed as a tool for the physician to assess risks and contribute to support better care for patients. The phenotyping of HFpEF could improve the characterization of patients, the definition of the most appropriate treatments, and the care pathways.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): Fédération française de cardiologie
Mortality patterns among patients with restrictive cardiomyopathy referred for CMR in a tertiary care center in Latin-America
Authors: Valderrama Achury M D , Higuera S A , Forero J F , Jaimes C P , Guerrero-Chalela C E , Rodriguez M J , Manrique F T , Barragan A , Zuluaga J D , Pino-Marin A , Medina H M 
Published: October 2022

Abstract

Background
Restrictive Cardiomyopathies (R-CMP) represent a wide array of conditions characterized by diastolic heart failure with important impairment in left ventricle filling pressures. These entities require different treatments, rendering etiological diagnosis a key component during the evaluation of these patients.

Purpose
Report the mortality of a select group of patients with R-CMP referred to CMR in a tertiary care center in Latin-America.

Methods
We analyzed all patients with CMR performed in our institution, including hospitalized and ambulatory patients, between 2016 and 2021. We extracted data of patients diagnosed by CMR with amyloidosis, hypertrophic cardiomyopathy (HCM), and endomyocardial fibrosis (EMF). All-cause mortality was extracted from national census data and analyzed using Kaplan-Meier survival estimates and log-rank test.

Results
Between June 1st, 2016, and December 31st, 2021, 5000 CMRs were performed at our institution. Among these, 317 (6.3%) patients were diagnosed with R-CMP by CMR as follows: 52 patients (16.4%) had amyloidosis, 250 patients had HCM (78.9%) and 15 patients (4.7%) had EMF. Of these, 40.7% were female (n=129), the median age was 63 yar-old (IQR 51–71) and 64.7% (n=205) were out-patients. At a mean follow-up of 33.3 months, there was a statistically significant difference in mortality between patients with amyloidosis (49,0%) and those with HCM and EMF (7,1% and 13,3%, respectively; P&lt;0.001), as described in Figure 1.

Conclusions
R-CMP represent a meaningful percentage of patients referred for CMR in our institution with different survival rates. Amyloidosis patients had a significantly higher mortality rate compared to HCM and EMF, at a relatively short follow-up. Increased access to CMR in our region for optimal diagnosis and early treatment may optimize prognosis in these types of patients.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): Self funding
Implications of the 2021 CKD-EPI cystatin C/creatinine eGFR equation for eligibility for therapy in HFrEF: insights from PARADIGM-HF
Authors: Tolomeo P , Kondo T , Butt J H , Desai A S , Lefkowitz M P , Rouleau J L , Solomon S D , Swedberg K , Zile M R , Campo G , Jhund P S , Packer M , McMurray J J V 
Published: October 2022

Abstract

Background
Estimated glomerular filtration rate (eGFR) is a key determinant of eligibility for many life-saving therapies in HFrEF. Recently, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) provided new equations based on creatinine (CKD-EPIcr), cystatin C (CKD-EPIcys) or both (CKD-EPIcyscr) that do not include race. These new equations may reclassify individuals, irrespective of race, from one eGFR category to another, with implications for eligibility for HFrEF treatments.

Purpose
To assess the difference between eGFR estimation using the 2021 CKD-EPIcyscr equation and the 2009 CKD-EPIcr and Modification of Diet in Renal Disease Study (MDRD)-4 equations which are still standard in many European laboratories.

Methods
We included patients from PARADIGM-HF with cystatin C and creatinine values available at the time of randomization. For each patient, baseline eGFRs were calculated using the 3 equations described. Our focus was on patients with chronic kidney disease (CKD) stages III–V.

Results
Overall, 1910 patients were eligible. Mean age was 67.3 (10.1) year and 385 (18.7%) were female. Using 2009 CKD-EPIcr, 779 patients were in CKD stages 3–5, of which 233 (30%) were reclassified to a better CKD stage (higher eGFR) with the 2021 CKD-EPIcyscr equation (Table 1). Similar reclassification was seen when comparing MDRD-4 with the 2021 CKD-EPIcyscr equation: 277 (33%) of 831 patients in CKD stages 3–5 were reclassified to a better CKD stage (Figure 1).

Conclusions
The 2021 CKD-EPIcyscr equation favourably reclassified CKD stage in a large percentage of patients with HFrEF and a low eGFR, potentially increasing the proportion of these patients considered eligible for guideline-recommended therapies.

Funding Acknowledgement
Type of funding sources: None.
Further prognostic stratification in patients with oscillatory ventilation with exercise: is there more to it than just ups and downs?
Authors: Lopes Da Cunha G J , Rocha B , Maltes S , Freitas P , Gama F , Aguiar C , Moreno L , Durazzo A , Mendes M 
Published: October 2022

Abstract

Introduction
Exercise Oscillatory Ventilation (EOV) has numerous definitions, but the common foundation is the presence of an oscillatory phenomenon of the ventilation/minute graph with a given amplitude and frequency. Recently, it was proposed that the presence of a delay in O2 consumption (VO2) peak to minute ventilation (VE) peak during ventilatory oscillation was a predictor of worse prognosis in patients with heart failure (HF) and left ventricular ejection fraction (LVEF) &lt;50%.
The aim of this work was to assess whether these characteristics add further prognostic value to the subset of patients with HF and EOV.

Methods
This was a single-centre retrospective cohort of consecutive patients with HF and LVEF &lt;50% that underwent cardiopulmonary exercise testing (CPET) from 2016–2020. EOV was defined as per Vainshelboim 2017 (≥3 consecutive cyclic fluctuations of ventilation during exercise, average amplitude over 3 ventilatory oscillations ≥5L and an average length of three oscillatory cycles 40s to 140s). The presence of EOV was evaluated by 3 independent observers after observing a VE over time plot. For the creation of this plot, data was collected as a rolling average of 5 consecutive breaths. The presence of EOV was established if at least 2 observers agreed on the classification.
Afterwards, a second graph was plotted, with both VO2 and VE over time and the mean delay between VO2 peak to VE peak during EOV was manually calculated (Figure 1).
The primary endpoint was a composite of time to all-cause death, heart transplantation or left ventricular assistance device (LVAD) implantation.

Results
Of the 285 patients, 78 (27%) were classified as having EOV. These HF patients were mostly male (75%) with a mean age of 58±12 years, mean LVEF 31±10% with 63% having ischemic etiology. During a median follow up of 27 (17 to 43) months, 4 LVAD implantations, 12 heart transplantations and 18 deaths. The rate of primary outcome was 19% and 36% at 1- and 2-years. The amplitude, frequency, and maximum number of EOV cycles were not associated with the development of the primary endpoint. Only the mean delay between VO2 peak to VE peak during EOV was predictive of time to primary endpoint, even when adjusted for peak VO2 and VE VCO2 slope (adjusted HR 1.06 95% CI 1.009–1.114) (Figure 2). The cut-off of 5 seconds for mean VO2 peak to VE peak delay seems to be the most useful to predict the primary outcome at 2 years, with a sensitivity of 48% and specificity of 84%.

Conclusion
This novel parameter seems to be the only EOV-related parameter to enable further stratification of prognosis in a cohort of patients with severe HF, with the best cut-off of mean delay between VO2 peak to VE peak during EOV being 5 seconds.

Funding Acknowledgement
Type of funding sources: None.