bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations of GPCR autoantibodies with clinical, histological, metabolic and hemodynamic features in non-ischemic heart failure patients
Authors: Karschnia M , Zweck E , Scheiber D , Heidecke H , Barthuber C , Kelm M , Roden M , Westenfeld R , Szendroedi J , Boege F 
Published: October 2022

Abstract

Background
Roughly one third of cases of chronic heart failure (HF) are caused by genetic predisposition, metabolic stress and cardiac inflammation. Animal studies suggest that heart-reactive autoantibodies, most notably those directed against G-protein-coupled receptors (GPCR), could also play a pathogenetic role in the disease. However, so far, a causal link between humoral GPCR-autoimmunity and human non-ischemic heart failure other than Chagas' cardiomyopathy remains unclear.

Purpose
Here, we investigated possible associations of GPCR autoantibodies with inflammatory, hemodynamic, metabolic and functional parameters in patients with chronic non-ischemic HF unrelated to Chagas' disease.

Methods
We prospectively included 95 patients with newly diagnosed non-ischemic heart failure of unknown origin. Basic cardiac characterization comprised transthoracic echocardiography, cardiac magnetic resonance imaging, coronary angiography and right heart catheterization with endomyocardial biopsy. Mitochondrial oxidative phosphorylation capacity and coupling was measured using high-resolution respirometry in permeabilized myocardial fibers. A panel of candidate GPCR-autoantibodies was determined by validated and certified immune-assays in peripheral venous blood of the HF-patients and 60 matched healthy individuals. Results were normalized to total IgG.

Results
Among 10 candidate GPCR-autoantibodies determined, only autoantibodies for α1-adrenergic receptor (α1AR), β1-adrenergic receptor (β1AR), muscarinic receptor M5 (M5AR), angiotensin II receptor type 1 (AT1R) and type 2 (AT2R) exhibited HF-associated alterations:
Autoantibodies against β1AR, M5R and AT2R were increased. Autoantibodies against α1AR and AT1R were decreased (Figure). These alterations were significant (p&lt;0.01), but not, or only weakly, correlated with markers of cardiac inflammation, cardiac damage, hemodynamics, endomyocardial histology or left ventricular inflammation judged by T2-mapping.
However, in HF-patients, increased AT2R autoantibodies were associated with improved myocardial mitochondrial coupling (r=−0.27, p=0.021), and decreased AT2R autoantibodies were associated with insulin resistance (r=−0.24 p=0.027).

Conclusion(s)
Some previously postulated alterations of GPCR autoantibodies were confirmed in thoroughly characterized HF-patients. However, association of these alterations with cardiac function was not traceable, which argues against a specific pathogenic role. Our data are compatible with multifaceted interactions of GPCR-autoantibodies with the myocardium and potentially with glucose metabolism, possibly indicating a disease-modifying or compensatory role.

Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): Research comission of the Heinrich-Heine University Duesseldorf
Titin truncating variant cardiomyopathy and related sarcomere insufficiency causes high energy demand resulting in mitochondrial dysfunction, autophagosome formation, and apoptosis
Authors: Stroeks S L V M , Verdonschot J A J , Lunde I G , Henkens M T H M , Willemars M , Schianchi F , Luiken J F P , Wang P , Derks K , Krapels I P C , Vanhoutte E K , Jones E A V , Brunner H G , Nabben M , Heymans S R B 
Published: October 2022

Abstract

Background/Objectives
Titin truncating variants (TTNtv) are the most prevalent genetic cause of dilated cardiomyopathy (DCM), resulting in upregulation of cardiac transcripts of oxidative phosphorylation (1,2). However, the underlying molecular mechanism(s) and cellular consequences of these findings remain unknown.

Methods and results
To gain insight into the metabolic changes and cellular consequences of a TTNtv, metabolic, mitochondrial, and survival pathways were studied in human TTNtv DCM hearts and isolated cardiomyocytes of TTNtv mice. TTNtv resulted in a significant increase of cardiac transcripts of glycolysis, citric acid cycle, mitochondrial fission, autophagy, and apoptosis when comparing RNAseq in 24 TTNtv and 27 mutation-negative DCM cardiac biopsies. Furthermore, a decrease in the area of myofibrils in human TTNtv hearts (TTNtv vs. mutation-negative DCM: 46%, and 62%, P=0.001), and an increase of mitochondrial (49% and 31%, P=0,001) and autophagosome areas (4% and 2%, P=0.002) was observed using transmission electron microscopy (TEM). Similar patterns of cardiomyocyte disorganization and stress could be seen in TTNtv hearts of mice even without a phenotype. Additionally, observed swollen mitochondria by TEM and decreased quantity of OXPHOS proteins by immunoblotting in murine TTNtv hearts indicate mitochondrial stress. Mitochondrial oxygen consumption at baseline and the maximum respiration in TTNtv cardiomyocytes of mice increased by a factor of 1.8 and 1.5 respectively (both P≤0.05), compared to WT. Furthermore, palmitate oxidation in TTNtv cardiomyocytes increased by 1.3 fold (P=0.005) compared to WT mice, suggestive of increased energy demand in TTNtv.

Conclusion
Myofibrillar insufficiency in human TTNtv DCM augments the cardiac oxygen and energy consumption, leading to pronounced morphological and functional mitochondrial decompensation. Swelling, damage and fission of mitochondria is further characterized by autophagosome formation and increased apoptosis pathways in TTNtv hearts.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Double-Dose consortium by Dutch Cardiovascular Alliance (DCVA)
Clinical impact of chronic kidney disease on appendicular skeletal muscle mass and mortality in hospitalized patients with acute heart failure
Authors: Akiyama E , Konishi M , Sato R , Matsuzawa Y , Iwahashi N , Kosuge M , Ebina T , Sato N , Takeda S , Hibi K , Tamura K , Kimura K 
Published: October 2022

Abstract

Introduction
Heart failure (HF) is a clinical syndrome associated with diverse metabolic disturbances. Recent studies including ours suggest that skeletal muscle plays an important role in the pathogenesis of chronic HF and chronic kidney disease (CKD). However, the effect of renal function on skeletal muscle mass in HF remains unclear.

Purpose
The purpose of this study was to investigate the impact of chronic kidney disease on appendicular skeletal muscle mass in hospitalized patients with acute HF (AHF).

Methods
We assessed lean body mass by dual energy X-ray absorptiometry in 418 hospitalized patients with AHF (age 71±13, left ventricular ejection fraction (LVEF) 39±17%, estimated glomerular filtration rate (eGFR) at discharge 46±19 mL/min/1.73 m2). Low appendicular skeletal muscle mass index (ASMI, appendicular skeletal muscle mass/height2) was defined according to the Asia Working Group for Sarcopenia criteria (&lt;7.0 kg/m2 in male, &lt;5.4 kg/m2 in female). CKD was defined as eGFR &lt;60 mL/min/1.73 m2 at discharge.

Results
CKD was observed in 77% of hospitalized patients with AHF (eGFR ≥60 mL/min/1.73 m2, n=96, 23%, eGFR 30–59 mL/min/1.73 m2, n=233, 56%, eGFR &lt;30 mL/min/1.73 m2, n=89, 21%). ASMI positively correlated with eGFR (r=0.16, P=0.002). ASMI decreased according to CKD categories (eGFR ≥60 mL/min/1.73 m2; ASMI 6.75±0.14 kg/m2, eGFR 30–59 mL/min/1.73 m2; ASMI 6.24±0.08 kg/m2, eGFR &lt;30 mL/min/1.73 m2; ASMI 6.24±0.13 kg/m2, p=0.003, Figure 1). During a median follow-up of 37 months, 92 (22%) of 418 patients died. The combination of ASMI and CKD identified subgroups with a significantly different probability of all-cause death (log-rank test p&lt;0.001, Figure 2).

Conclusions
CKD was associated with decreased skeletal muscle mass in hospitalized patients with AHF. CKD and skeletal muscle mass independently correlated with mortality after AHF episode. The cross link between kidney and skeletal muscle might play an important role in the pathogenesis of AHF.

Funding Acknowledgement
Type of funding sources: None.
A clinical and echocardiographic score to differentiate pulmonary hypertension due to heart failure with preserved ejection fraction from idiopathic pulmonary hypertension: the PH-HFPEF score
Authors: Dardi F , Ballerini A , Guarino D , Donato F , Bertozzi R , Martini G , Magnani I , Manes A , Palazzini M , Galie' N 
Published: October 2022

Abstract

Background
One of the most challenging differential diagnoses in pulmonary hypertension clinical practice, is the discrimination between idiopathic pulmonary arterial hypertension (IPAH) and pulmonary hypertension due to heart failure with preserved ejection fraction (PH-HFpEF).

Aim
We elaborate a score (considering patient clinical history, demographics, and echocardiographic characteristics) that can predict, noninvasively, PH-HFpEF vs IPAH diagnosis.

Methods
Data were prospectively collected on 466 consecutive patients with a final diagnosis of IPAH or PH-HFpEF referred to a single tertiary pulmonary vascular disease centre. Data included clinical history, demographics, and parameters of an electrocardiogram and a transthoracic echocardiogram. A multivariate regression model was developed to predict a PH-HFpEF diagnosis, and an integer risk score was generated using adjusted regression coefficients of the multivariate logistic regression analysis.

Results
At the multivariate logistic regression a high ratio between left and right ventricular dimensions, a history of atrial fibrillation (AF), a high body mass index (BMI), a reduced mitral deceleration time and a high E-wave at trans-mitral doppler, an advanced age and a high right ventricular fractional area change (FAC) were predictors of PH-HFpEF. The derived PH-HFPEF score is shown in Table 1 and, with a cut-point ≥11, it yielded a specificity/sensitivity, respectively, for the diagnosis of PH-HFpEF, of 100%/49% with an AUC of 0.987.

Conclusions
The PH-HFPEF score can predict PH-HFpEF vs IPAH. The PH-HFPEF score may be used to potentially avoid an invasive diagnostic testing in almost half of PH-HFpEF patients.

Funding Acknowledgement
Type of funding sources: None.
Insight into the relationship between heart rate and mortality in patients in sinus rhythm with heart failure with preserved ejection fraction
Authors: Nakagawa Y , Sairyo M , Miyazawa K , Tamaki S , Yano M , Hayashi T , Yamada T , Yasumura Y , Hikoso S , Sotomi Y , Sakata Y 
Published: October 2022

Abstract

Background
There are several reports showing that elevated heart rate (HR) is associated with poor outcomes in patients in sinus rhythm (SR) with heart failure with preserved ejection fraction (HFpEF), although the association is weak or none in HFpEF patients with atrial fibrillation (Af). However, in previous studies, cardiac and non-cardiac factors which may be associated with elevated HR, have not been fully adjusted for.

Purpose
The purpose of this study is to explore covariates of elevated HR and to investigate the relationship between heart rate and mortality in HFpEF patients in SR.

Methods and results
Of the 1161 patients, who registered prospective multicenter, observational study of patients with HFpEF (PURSUIT-HFpEF), 726 patients in SR were examined. We performed laboratory testing and echocardiography in the compensated stage (in stable condition after treatment of acute decompensated HF). Geriatric nutritional risk index (GNRI) was calculated as nutrition index. Resting heart rate (HR) was analyzed as categorical (tertiles, T1–3). We followed the patients for median of 598 days (interquartile range 329–1028 days) to observe the outcome all-cause mortality.
The Kaplan analysis revealed that there was a significant difference between heart rate and mortality (log-rank, p=0.001). Characteristics were compared between patients in T1 (HR ≤63) and T3 (HR ≥75). There were no differences in cardiac factors between patients in T1 and T3. C-reactive protein (CRP) was significantly higher in patients in T3 than those in T1 (p=0.0004,). GNRI was significantly lower in patients in T3 than those in T1 (p=0.001). After adjustment for covariates including N-terminal pro-B type natriuretic peptide and estimated glomerular filtration rate, CRP and GNRI significantly correlated with HR (continuous variable) by multiple regression analysis (beta-coefficient = 1.52, p=0.003 and beta-coefficient = −0.14, p=0.04, respectively). Taking T1 as the reference, multivariable Cox regression analysis revealed that T3 was independently associated with mortality (hazard ratio: 2.10, 95% confidence interval: 1.33–3.32, p=0.001).

Conclusion
Although elevated HR was associated with enhanced inflammation and malnutrition, it itself was an independent predictor of death in HFpEF patients in SR.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): Roche Diagnosis K.K.Fuji Film Toyama Chemical Co. Ltd.
Right atrial function in HFpEF in sinus rhythm vs. atrial fibrillation
Authors: Schoenbauer R , Hana F , Duca F , Koschutnik M , Dona C , Nitsche C , Sponder M , Lenz M , Loewe C , Beitzke D , Hengstenberg C , Mascherbauer J , Kammerlander A A 
Published: October 2022

Abstract

Aims
We sought to study the prognostic impact of right atrial (RA) size and function in patients with heart failure with preserved ejection fraction (HFpEF) in sinus rhythm (SR) vs. atrial fibrillation (AF).

Methods and results
Consecutive HFpEF patients were enrolled and indexed RA volumes and emptying fractions (RA-EF) were assessed by cardiac magnetic resonance imaging (CMR). For patients in SR during CMR feature tracking of the RA wall was performed (Figure 1). In addition, all patients underwent right and left heart catheterization, 6 min walk test, and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) evaluation. We prospectively followed patients and used Cox regression models to determine the association of RA size and function with a composite endpoint of heart failure hospitalization and cardiovascular death. A total of 188 patients (71% female patients, 70±8 years old) were included of whom 96 (51%) were in SR. Eighty-five patients reached the combined endpoint during a follow-up of 72 (33–101) months. After multivariate cox regression analysis adjusted for age, NT-proBNP level, right ventricular ejection fraction and HF functional class, impaired RA strain (Figure 1A) (HR 0.959; 95% CI [0.924–0.996], P=0.024), RA conduit strain (Figure 1A) (HR 0.944; 95% CI [0.898–0.993], P=0.027) and RA conduit strain rate (Figure 1B) (HR 0.990; 95% CI [0.883–0.998], P=0.013) were significantly associated with adverse outcome for patients in SR (Table 1). In persistent AF, no RA imaging parameter was related to outcome after multivariate regression analysis.

Conclusions
In HFpEF patients in SR, CMR parameters of impaired RA conduit function show the best association with adverse cardiovascular outcome. In persistent AF, RA parameters lose their prognostic ability.

Funding Acknowledgement
Type of funding sources: None.
Long-term cardiac adverse effects after modern Hodgkins lymphoma treatment
Authors: Bjerring A W , Smeland K H B , Baerug I , Haugaa K H , Kiserud C E , Edvardsen T , Sarvari S I 
Published: October 2022

Abstract

Background
Hodgkin's lymphoma (HL) frequently affects both children and young adults. Traditional treatment of HL is effective but associated with a life-time prevalence of cardiac disease exceeding 50%. Treatment protocols were modified in 1997 to reduce cardiotoxicity, primarily by reducing both radiation fields and doses.

Purpose
To assess the long-term impact of the modified treatment protocols on left ventricular cardiac function.

Methods
HL survivors (n=244) treated with anthracycline-based chemotherapy using modified treatment protocols in 3 centres in Norway between 1997 and 2007 were included in this cross-sectional study. Of these, 130 (53%) also received mediastinal radiotherapy. They were compared to controls recruited from the general population (n=58) matched for age, sex, and risk-factors. Echocardiography was performed in all subjects.

Results
The participants were on average 46±9 years old and had received treatment on average 17±3 years before examination. Echocardiographic parameters are shown in the table. Reduced left ventricular (LV) ejection fraction (EF) (&lt;52%) was found in 19 HL-survivors and three controls (13% vs. 6%, p=0.24). Reduced LV global longitudinal strain (GLS) (&gt; −18.0%) was found in 41 HL survivors and three controls (25% vs. 6%, p&lt;0.05). There was no difference in prevalence of reduced GLS between HL survivors who received mediastinal radiotherapy and those who did not (26% vs. 24%, p=0.70).

Conclusion
While a minority of HL survivors did have a slight reduction in longitudinal deformation, the effect was small and importantly, we found no difference in EF between HL survivors treated with modified protocols and controls. Mediastinal radiotherapy did not seem to increase the prevalence of reduced cardiac function in HL survivors.

Funding Acknowledgement
Type of funding sources: Public hospital(s). Main funding source(s): South-Eastern Norway Regional Health Authority
Pulmonary artery pressure-guided therapy in patients with heart failure using the CardioMEMS device and HF readmissions: analysis of the National Readmissions Database
Authors: Briasoulis A , Kishino Y , Kuno T , Malik A 
Published: October 2022

Abstract

Background
Pulmonary artery pressure (PAP)-guided therapy in patients with heart failure (HF) using the CardioMEMS device (CMM), an implantable PAP sensor, has shown to reduce HF hospitalizations in previous studies. We sought to evaluate the clinical benefit of the CMM device in regard to 30-day, 90-day and 180-day readmission rates in real-world usage.

Methods
We queried the National Readmission Database (NRD) to identify patients who underwent CMM implantation (ICD 9 & 10 codes) between the years 2014 to 2019 and studied their HF readmissions. We compared CMM patients and their readmissions with a matched cohort of patients with HF without CMM. Multivariable Cox regression analysis was performed to adjust for other predictors of readmissions.

Results
Prior to matching we identified 5,326,530 weighted HF patients without CMM and 1842 patients with CMM. After propensity score matching for several patients and hospital related characteristics, the cohort consisted of 1839 patients with CMM and 1924 with HF without CMM. Before matching, CMM patients were younger (67.0±13.5 years vs 72.3±14.1 years, P&lt;0.001), more frequently males (62.7% vs 51.5%, P&lt;0.001), with higher rates of prior percutaneous coronary intervention (16.9% vs 13.2%, P=0.002), peripheral vascular disease (29.6% vs 17.8%, P&lt;0.001), pulmonary circulatory disorder (38.7% vs 23.2%, P&lt;0.001), atrial fibrillation (51.2% vs 45.3%, P=0.002), prior left ventricular assist device (1.8% vs 0.2%, P&lt;0.001), high income (32.2% vs 16.4%, P&lt;0.001) and acute kidney disease (43.8% vs 29.9%, P&lt;0.001). Readmission rates at 30-days were 17.3% vs. 20.9% for patients with vs. without CMM respectively and remained statistically significant after matching (17.3% vs. 21.5%, p=0.002). The rates of 90-day (29.1% vs 36.5%, p=0.002) and 180-day (39.6% vs. 46.6%, p=0.009) readmissions were lower in the CMM group. In a multivariable regression model, CMM was associated with lower risk of readmissions (HR, 0.75, 95% CI 0.63–0.89, p=0.001).

Conclusion
The CMM device was associated with reduced HF rehospitalization rates in a nationally representative cohort of HF patients.

Funding Acknowledgement
Type of funding sources: None.
Hemodynamics of acute decompensated heart failure in patients with very low NP levels
Authors: Subramanian V , Segar M , Wang T W , Pandey A P 
Published: October 2022

Abstract

Background/Introduction
Natriuretic Peptides are hormones secreted by the heart in response to cardiomyocyte stretch. The principal biological action of NP is natriuresis, diuresis and vasodilation. These are salutary effects in acute decompensated heart failure (ADHF). Some patients admitted with ADHF have very low NP levels. It is unknown if this is due to a defect in biosynthesis or inadequate stimulation.

Purpose
We analyzed data from the National heart Lung and Blood institute sponsored ESCAPE trial which included patients admitted with acute decompensated heart failure who underwent hemodynamic assessment with pulmonary artery catheters at admission and after diuresis. Our aim was to evaluate if there were characteristic hemodynamic findings among patients with very low NP levels at admission which differed from those who had elevated NP levels at admission.

Methods
We performed a secondary analysis of the ESCAPE Trial. We defined very low BNP as patients with BNP level at admission &lt;50 pg/mL. We then compared baseline characteristics between the groups. Continuous groups were compared using X-square test, and Categorical variables were compared using Wilcoxon-signed-Rank-Sum test. We compared groups by Demographic, Anthropometric, Laboratory, and Functional status. We then performed propensity matching on Age, Sex, and BMI and then compared groups.

Results
25/351 patients had very low BNP (&lt;50pg/mL). Patients in the low BNP group had higher BMI than those with elevated BNP (35.8 vs. 28.9 p&lt;0.001). The cohort with low BNP was younger. (50.2 vs. 56.4 p=0.029). In propensity matched cohorts of Age, Sex, BMI. Cardiac output was elevated in the low BNP cohort. (5.2 vs. 3.9 p=0.011). However, Cardiac Index was similar between the groups (2.2 vs. 2.0 p=0.244). Patients in the Low NP group had lower pulmonary capillary wedge pressure (PCWP) compared to those with elevated BNP. (16.5 vs. 25.4 p=0.023). The groups had similar RA pressures (11.5 vs. 13.0 p=0.515). The calculated transmural pressure (PCWP – RA pressure) was lower in the low NP group. There was a reduction in BNP levels at discharge among the group with elevated BNP at admission (1072.6 (baseline) 798.8 (discharge)) In the low BNP group there was an increase in BNP at time of discharge (20.2 (baseline) to 172.7 (discharge)). In follow-up, the low BNP group had reduction in BNP compared to their discharge levels. The group with elevated BNP had elevated BNP at follow-up in 3 and 6 months. Length of stay was shorter in the Low BNP group (6.2 vs. 8.8, p=0.052).

Conclusion(s)
In this secondary analysis of the ESCAPE trial, we find that those patients admitted with ADHF who have unexpectedly low BNP have lower transmural pressures at baseline compared to those who have elevated BNP levels. This suggests that there may not be adequate stimulus for cardiac wall distention and release of BNP.

Funding Acknowledgement
Type of funding sources: None.