bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phenotype groups in atrial cardiomyopathy and their prognosis
Authors: Ilieva R , Kinova E , Slavchev B , Georgieva N , Kalaidzhiev P , Goudev A 
Published: October 2024

Abstract

Background
Atrial cardiomyopathy (ACM) includes patients with heterogenous demographic characteristics and comorbidities. Defining phenotype groups with similar clinical characteristics is important for the effective treatment of these patients, and for their prognosis and prevention of ACM.

Purpose
To conduct a cluster analysis that could help us in phenotyping ACM and exploring the clinical complexity of this entity.

Methods
We performed a hierarchical cluster analysis based on Ward’s Method using 10 clinical binary variables (hypertension, diabetes mellitus, heart failure, obesity, chronic obstructive pulmonary disease, cancer, coronary artery disease, sinus node dysfunction or atrio-ventricular block, implanted pacemaker, and ischemic stroke), identifying the optimal number of clusters. We investigated differences in demographic, laboratory and echocardiographic parameters, and treatment between defined clusters, and assessed the impact of these factors on prognosis.

Results
Of 724 evaluated consecutive patients with dilated left atrium only 200 met the criteria for advanced atrial cardiomyopathy, defined as severely dilated left atrium with volume index (LAVI) ≥ 48 ml/m2, preserved left ventricular systolic function - ejection fraction ≥ 50%, without an overt valvular or ventricular disease, and were included in the analysis. Mean age of the studied population was 73.91 ± 9.74 years, 58 % of them were women. We identified 4 clusters: cluster 1 (n = 73, 36%) were younger overweight patients with paroxysmal atrial fibrillation (AF); cluster 2 (n = 56, 28%) - old patients with congestive heart failure (CHF) and low body mass index (BMI); cluster 3 (n = 34, 17%)- diabetic patients with obesity and CHF; and cluster 4 (n = 37, 19%) old patients with tachycardia-bradycardia syndrome, implanted pacemakers, and long -standing AF. Over a mean follow up of 20.6 months cluster 2 had the highest mortality rate (28.6%), followed by cluster 3 (20.6%), compared to the lower mortality rate of cluster 1 and 4 (11% and 10.8%, respectively, p=0.047). The presence of heart failure (HR 4.4, CI 1.5 ÷12.7, p=0.006), cancer (HR 3.3, CI 1.6 ÷ 6.9, p=0.002) and greater than moderate tricuspid regurgitation (HR 5.4, CI 2.6 ÷ 11.3, p&lt;0.001) were predictors of poor outcome.

Conclusion
In patients with advanced atrial cardiomyopathy, four main clusters were identified, differentiated by distinct comorbidities. Both clinical and echocardiographic parameters were found to be associated with an increased risk of mortality.Phenotype clusters of ACMKaplan-Meier curves of clusters
Post-prandial acyl ghrelin infusion in heart failure patients increases gastric emptying rate
Authors: Webb D , Hage C , Ljung-Faxen U , Pironti G , Thorvaldsen T , Andersson D C , Stahlberg M , Lund L H , Hellstrom P M 
Published: October 2024

Abstract

Background
Acyl ghrelin (ghrelin) increases cardiac output (CO) and contractility in patients with heart failure with reduced ejection fraction (HFrEF). In healthy humans, ghrelin increases gastric emptying rate (GER) and hunger, a potential add-on benefit for HFrEF patients suffering from cachexia with symptoms of delayed gastric emptying and loss of appetite.

Aim
Determine if post-prandial ghrelin infusion increases GER and hunger in HFrEF patients; compare to CO.

Methods
This study was a component of a double-blind placebo-controlled trial of acyl ghrelin vs. placebo in HFrEF. Patients (n=29) arrived fasted and received a 500 kcal breakfast and 1.5 g paracetamol. They next received placebo (vehicle, n=15) or ghrelin infusion (0.1 µg/kg/min, n=14) for 120 min. Blood was tapped for plasma at 0, 30, 60, 120 and 150 min into the meal. Plasma concentration of paracetamol was measured to assess GER of a liquid bolus. Hunger scores and CO were recorded. Mann-Whitney rank sum test was used for statistics.

Results
Paracetamol peaked at 30 min in 8 of 14 (57%) in the ghrelin treatment group versus 1 of 15 (7%) in the placebo group (P=0.004, Fig 1). Remaining patients peaked at later time points. There were no anomalous peaks at 0 min baseline or 2880 min (2 days). The ghrelin treatment group data was segregated into rapid (peak at 30 min, n=8) and slow (peak &gt;30 min, n=6) GER subgroups. The rapid subgroup had a ghrelin treatment effect on CO (one-way repeat measures) (P&lt;0.001, Fig 2). Baseline (t=0) CO for the rapid GER subgroup was 4.06 ±1.41 L/min (median ±SD) and 3.95 ±0.62 L/min for the slow GER subgroup (P=0.31). Data points shown are median ± SEM, each patient normalized to own baseline (100%); * P&lt;0.05, ** P&lt;0.01, *** P&lt;0.001, pairwise comparison to baseline. Hunger gradually increased. The greatest increase in hunger was at 150 min, at which time median fold increase in hunger relative baseline was 1.6 (placebo), 1.7 (ghrelin, slow GER) and 2.3 (ghrelin, rapid GER). These hunger differences between groups did not reach significance. However, this trend was consistent with ghrelin induction of hunger, especially in those with potent GER and CO responses.

Conclusions
Ghrelin increases GER, and potentially hunger, in HFrEF patients in addition to increasing CO. Some HFrEF patients may benefit from this add-on effect.Fig 1.Time of paracetamol peak.Fig 2.Cardiac output.
An Elevated FIB-4 Score is associated with the severity of heart failure
Authors: Bielecka-Dabrowa A , Sakowicz A , Banach M , Slot M 
Published: October 2024

Abstract

Background
Liver disease and heart failure (HF) are known to be closely associated. Non-invasive tests (NIT), such as the FIB-4 score, have been recommended by different guidelines to rule out advanced liver fibrosis and to stratify the risk of liver-related outcomes in patients with chronic liver diseases.

Purpose
Thus, our goal was to evaluate the connection between the FIB-4 index, heart failure, associated comorbidities, and cardiological biomarkers that predict the risk of liver fibrosis in patients with heart failure.

Methods
HF patients hospitalized in the cardiology department were divided into a group with an FIB-4 index &lt;1.3 (indicating a low risk of liver fibrosis) (n=53) and a group with an FIB-4 index ≥1.3 (indicating intermediate and high risk of fibrosis) (n=59). Clinical examinations, laboratory results, echocardiography with Vivid E95-GE Healthcare, non-invasive body mass analysis with Body Composition Analyzer (Tanita Pro), and measurements of NT-proBNP, growth differentiation factor 15 (GDF-15), galectin-3, fatty acid-binding protein (FABP), copeptin, and vascular endothelial growth factor (VEGF) concentrations were performed.

Results
The patients with an FIB-4 index ≥1.3 had significantly higher: left ventricular volume index (LAVI) (p=0.004), E/E’ ratio (p=0.004) and lower left ventricular ejection fraction (p=0.003) compared to group with low risk of liver fibrosis. There were no differences in body mass compartments between groups except for ECW/TBW (%) - an index of body water distribution, which was lower in low-risk liver fibrosis group (p=0.0002). Patients with an FIB-4 index ≥1.3 had also lower: GFR MDRD (median 59.95 vs 85.1 mL/min/1.73 m²; p&lt;0.001), total cholesterol (116.5 vs 15 mg/dL; p=0.002), LDL cholesterol (median 56 vs 93 mg/dL; p&lt;0.0001) and HDL cholesterol (median 39 vs 47 mg/dL; p=0.03). Regarding heart failure biochemical biomarkers, patients with low risk of liver fibrosis had significantly lower level of NT-proBNP (median 37 vs 161 pg/ml; p&lt;0.0001), GDF-15 (median 399.6 vs 898.9 pg/ml; p&lt;0.0001) and FABP (median 101 vs 264,7 pg/ml; p=0.04). In a multiple logistic regression model the factors that were independently associated with the risk of liver fibrosis in HF patients based on an FIB-4 index were GDF-15 &gt;724 pg/ml (OR 33.7, 95%CI: 6.5-174.2; p=0.0001), and NT-proBNP &gt;129 pg/ml (OR 19.9, 95% CI: 3.8-103; p=0.0001) (Figure 1)

Conclusion
Our study suggests association between an elevated FIB-4 score and heart functions, and kidney impairment with fluid overload but not with higher total and low density cholesterols fractions or percentage of fat. Higher GDF-15 and NT-proBNP levels are independently associated with the risk of liver fibrosis based on an FIB-4 index. FIB-4 index in HF patients is an easy method to monitor the risk of liver fibrosis and might help to predict the HF progression and CVD complications.
Obesity and renal impairment in patients with heart failure and reduced ejection fraction: another obesity paradox?
Authors: Matsumoto S , Henderson A D , Shen L , Desai A S , Swedberg K , Claggett B L , Lefkowitz M P , Rouleau J L , Vaduganathan M , Packer M , Zile M R , Jhund P S , Solomon S D , Mcmurray J J V 
Published: October 2024

Abstract

Background
Obesity is associated with poor cardiovascular outcomes in patients with HF and reduced ejection fraction (HFrEF). However, whether obesity is associated with worse kidney outcomes in HFrEF has not been evaluated.

Purpose
To estimate the association between obesity and change in estimated glomerular filtration rate (eGFR) over time in patients with HFrEF.

Methods
In this post hoc analysis of the PARADIGM-HF trial, body mass index (BMI) and eGFR was collected in 8,389 patients. Change in eGFR over time was assessed according to baseline BMI (normal weight: BMI &lt;25.0, overweight: BMI 25-29.9, and obesity: BMI ≥30).

Results
The number of patients in each BMI category was: 2,421 (BMI &lt;25.0), 3,249 (BMI 25-29.9), and 2,719 (BMI ≥30), respectively. Patients with obesity were younger but had worse health status (worse NYHA class and KCCQ scores) and had more comorbidities including diabetes mellitus and hypertension. At baseline, eGFR was lower in patients who were overweight (BMI 25-29.9) and obese (BMI ≥30), compared to those with normal weight. Urine albumin-creatinine ratio (UACR) and kidney injury molecule-1 (KIM-1) were also higher in patients with obesity. However, the rate of change in eGFR per year (eGFR "slope") in the overall cohort did not differ according to BMI: change in eGFR per year was -1.8 [-2.1, -1.6] mL/min/1.73m2 for the normal weight category, -1.6 [-1.8, -1.3] mL/min/1.73m2 for those who were overweight, and -1.5 [-1.8, -1.3] mL/min/1.73m2 for those with obesity; P=0.21) (Figure 1). Among those without diabetes at baseline, those who were obese had a significantly less steep eGFR slope compared to patients in the other BMI categories. In those with diabetes at baseline, the eGFR slope was steeper than in patients without diabetes but was similar across all three BMI categories (Figure 2).

Conclusions
Although baseline kidney function was more impaired in HFrEF patients with obesity, high BMI was not associated with a more rapid subsequent rate of decline in eGFR.
Figure 1. eGFR slope over time according to BMI at baseline in patients with HFrEF in PARADIGM-HF
Figure 2. eGFR slope over time according to BMI at baseline in patients with HFrEF in PARADIGM-HF with and without diabetes at baselineFigure 1Figure 2-A and 2-B
Long-term clinical-pathologic results of enzyme replacement therapy in pre-hypertrophic fabry disease cardiomyopathy
Authors: Frustaci A , Verardo R , Galea N , Alfarano M , Marchitelli L , Sansone L , Belli M , Cristina M , Frustaci E , Russo M A , Chimenti C 
Published: October 2024

Abstract

Background
Limited ability of ERT in removing Gb-3 from cardiomyocytes is recognized for advanced FDCM. Pre-hypertrophic FDCM is believed to be cured or stabilized by ERT. However, no pathologic confirmation is available. We report here in the long-term clinical-pathologic impact of ERT on pre-hypertrophic FDCM.

Purpose
Long-term clinical-pathologic impact of ERT on pre-hypertrophic FDCM.

Methods
Fifteen Fabry patients with LVMWT ≤ 10.5 mm at CMR required EMB because of angina and/or ventricular arrhythmias. EMB showed coronary small vessel disease in angina cohort and vacuoles in smooth muscle cells and cardiomyocytes around 20% of cell surface containing myelin bodies at electron microscopy. Patients received α-agalsidase in 8 and β-agalsidase in 7 cases. Both groups referred symptoms improvement except 2 patients treated with α- and β-agalsidase respectively. After ERT administration ranging from 4 and 20 years all patients had control CMR and LVEMB because of persistence of symptoms or patients enquiry on disease resolution.

Results
In 13 asymptomatic FDCM patients, LVMWT and LV-mass, cardiomyocyte diameter, vacuole surface/cell surface ratio and vessels remained unchanged or minimally increased (LV-mass augmented by &lt; 2%) even after 20 years observation and storage material was still present at electron microscopy. In 2 symptomatic patients, FDCM progressed with larger and more engulfed by Gb-3 myocytes being associated to myocardial virus-negative lymphocytic inflammation.

Conclusions
ERT stabilizes storage deposits and myocyte dimensions in 87% of patients with pre-hypertrophic FDCM. Gb-3 is never completely removed even after long-term treatment. Immune-mediated myocardial inflammation can overlap limiting ERT activity.
Figure Legend
Patient 11 (24-year-old man) with genetic and biopsy-proven diagnosis of FDCM before and after 20 years ERT.
CineMR (A,B) and LGE (C,D) images, performed at baseline (A,C) and 20 years after ERT (B,D) show normal LV wall thickness (8mm and 10 mm) and absence of fibrotic areas.
Panel E and F represent semithin section of Epon-embedded EMB samples, stained with basic fuchsin, showing mildly hypertrophied cardiomyocytes containing storage material that result unmodified after long-term ERT administration.
Panel G and H are ultrastructural evidence of storage material to consist of myelin bodies (panel G) that remain unchanged after ERT (Panel H).
Clinical and financial implications of inpatient and outpatient management strategies for worsening heart failure
Authors: Greene S J , Kaltenbach L A , Fonarow G C , Chiswell K , Kittipibul V , Hernandez A F , Hammill B G , Butler J , Felker G M 
Published: October 2024

Abstract

Introduction
Hospitalizations for worsening heart failure (HF) represent an enormous public health and financial burden. Accordingly, select centers have developed outpatient worsening HF (WHF) management strategies focused on care in emergency departments (ED), observation units, or intravenous (IV) diuretic clinics. However, broad use of these outpatient strategies and the associated outcomes and healthcare costs remain unclear.

Methods
Among US Medicare beneficiaries age ≥65 years hospitalized for HF in the Get With The Guidelines Heart Failure registry 2010-2018, we identified patients with a post-discharge non-fatal WHF event. Patients were divided into 4 mutually exclusive groups defined by type of first post-discharge WHF event (HF hospitalization, ED visit with ED discharge, observation unit stay, and outpatient clinic visit with IV diuretics). Following each type of WHF event, mortality, home-time (days alive and out of any healthcare institution), and healthcare costs were compared over the subsequent 12-months. Costs of the initial WHF management strategy were also assessed.

Results
Among 181,827 patients hospitalized for HF, during the 12-months post-discharge, 83,971 (46.2%) survived with no WHF event, 36,697 (20.2%) died prior to a WHF event, and 61,159 (33.6%) had a WHF event. Of patients with a WHF event, 48,612 were managed with HF hospitalization (79.5%), 8,139 (13.3%) with an ED visit, 1,767 (2.9%) with an observation unit stay, and 2,641 (4.3%) with an outpatient IV diuretic visit.
Compared with HF hospitalization, patients with WHF managed in the ED, observation unit, or IV diuretic clinic experienced lower subsequent mortality (Figure 1). Mean 12-month home-time was lowest following HF hospitalization (207 ± 144 days), intermediate following ED (238 ±136 days) and outpatient IV diuretic visits (252 ±128 days), and highest following observation unit stays (277 ± 125 days). For the initial WHF event, median (25th, 75th) total per-patient costs were highest for HF hospitalization and lowest for outpatient IV diuretic visits (Figure 2). Over the 12-months following the WHF event, median total per-patient costs were highest following outpatient IV diuretic visits, intermediate following HF hospitalization and ED stays, and lowest following observation unit stays.

Conclusions
In a nationwide analysis of older US adults, 1 in 5 episodes of recurrent WHF were exclusively managed as an outpatient within the ED, observation unit, or IV diuretic clinic. High rates of death and substantial reductions in home-time occurred following WHF regardless of inpatient or outpatient management, but were worse following HF hospitalization. Outpatient IV diuretic administration was the least expensive initial management strategy, but was associated with the highest per-patient costs over the subsequent 12 months.
The impact of the 2022 definition of pulmonary hypertension on long-term clinical outcomes in patients with heart failure with preserved ejection fraction
Authors: Sera F , Ohtani T , Seo M , Hayashi T , Yano M , Nakagawa A , Nakagawa Y , Tamaki S , Yamada T , Yasumura Y , Hikoso S , Okada K , Nakatani D , Sotomi Y , Sakata Y 
Published: October 2024

Abstract

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Backgrounds: In recent years, the definitions of pulmonary hypertension (PH) have been revised for early diagnosis and risk stratification of patients with PH. Using the 2015 definitions, the development of a precapillary component of PH in addition to a postcapillary PH was associated with right heart dysfunction and poor prognosis in patients with heart failure (HF) with preserved ejection fraction (HFpEF). However, the prognostic impact of revised definitions of PH in patients with HFpEF has not been fully evaluated.

Purpose
We investigated the impact of the 2018 and 2022 ESC/ERS definitions of PH on long-term clinical outcomes using data from a prospective, multicenter, observational study of patients with HFpEF (PURSUIT-HFpEF).

Methods
A total of 250 patients hospitalised with acute HF who underwent right heart catheterisation after initial HF treatment were divided into PH categories according to the 2018 and 2022 definitions: isolated postcapillary PH (Ipc-PH), precapillary PH, combined postcapillary and precapillary PH (Cpc-PH), and unclassified PH. The incidence of the composite endpoint of all-cause death and HF rehospitalisation after discharge was compared across the PH categories.

Results
The overall prevalence of PH defined as a mPAP &gt; 20 mmHg was 54%. Applying the 2022 definition, 42 patients (17%) were reclassified as either precapillary PH or Cpc-PH, resulting in a significant increase in the propotion of patients classified as having PH with a precapillary component (precapillary PH and Cpc-PH) compared with the 2018 definition (26% vs. 11%, p&lt;0.0001). At a median follow-up of 822 days after discharge, PH with a precapillary component was associated with poor clinical outcomes according to the 2018 definition (Figure 1A), but according to the 2022 definition, clinical outcomes did not differ across the PH categories (Figure 1B). PVR ≥3 Wood units (WU) was a significant prognostic indicator, but there was no significant difference between the PVR 2-3 WU and PVR ≤2 WU categories (Figure 2).

Conclusions
The 2022 definition showed no association between PH classification and clinical outcomes. In patients with HFpEF, PVR ≥3 WU was identified as the key factor increasing the risk of all-cause death and HF hospitalisation.Figure 1Figure 2
Remote management of worsening heart failure events and subsequent rate of emergency department admission
Authors: Florence J , Ploux S , Riocreux C , Eschalier R 
Published: October 2024

Abstract

Background
Worsening heart failure (WHF) is the leading cause of hospitalization among individuals aged ≥ 65 years and constitutes a substantial burden for both the patient and the healthcare systems. Moreover, heart failure contributes to exacerbate the pressure on emergency departments which are involved in 64% of heart failure hospital admission (1). Remote management of heart failure as been shown to reduce the number of days lost due to unplanned cardiovascular hospitalizations and all-cause mortality (2, 3), but little is known about the effect on the emergency healthcare use.
We aimed to describe the effect of a telemonitoring program on the rate of emergency admissions for WHF in chronic heart failure patients.

Methods
All patients enrolled in the heart failure remote management program of two French centers between 13 April 2020 and 31 January 2023 were included in the study. Follow-up data were collected until 31 January 2023. Inclusion criteria were chronic heart failure (HF) with New York Heart Association ≥II and an elevated B-type natriuretic peptide (BNP &gt; 100 pg/mL or N-terminal-pro-BNP &gt; 1000 pg/mL). Remote evaluation included measurements of body weight, blood pressure, heart rate, symptoms, biochemical parameters, and data from cardiac implantable electronic devices when available.

Results
A total of 1,095 patients (72±11.8 years old, 69.7% male), were followed for a median [IQR] of 437 [182; 739] days with a mean adherence to the remote monitoring system of 67.6±30.3%. Over this period, 198 (18.1%) patients had 949 WHF events, the majority of whom were remotely detected: 830 (87.5%). Overall, 246 (26%) of the WHF episodes required hospitalisation and 109 (11%) prompted an emergency department visit. When the WHF event was remotely detected, hospitalization was only required in 127 (15%) cases and the rate of emergency department visit was reduced to 3%.

Conclusion
In HF patients engaged in a multiparametric remote management program, the rate of emergency department admission is very low. Adopting such a strategy for patients with chronic HF may be useful in reducing emergency department overcrowding.Baseline characteristics of patientsPatients course and use of resources
Cardiomyocyte regeneration in human myocarditis
Authors: Frustaci A , Foglio E , Limana F , Magnocavallo M , Frustaci E , Lupacchini L , Verardo R 
Published: October 2024

Abstract

Background
Newly generated cardiomyocytes (NGC) concur to recovery of human myocarditis.

Purpose
describe NGC’s contribute with age and their modality of myocardial homing and integration.

Methods
We retrospectively assessed NGC in 213 consecutive patients with endomyocardial biopsy diagnostic for myocarditis, normal coronaries and valves. Tissue samples were processed for histology and immune-histochemistry for CD3+ T lymphocytes, alpha-sarcomeric-actin, junctional connexin-43, Ki-67, phosphorylated STAT3 (p-STAT3) and Western Blot (WB) for HMGB1. Frozen samples were analyzed with polymerase chain reaction (PCR) for cardiotropic viruses. Controls included 20 normal surgical biopsies. NGC were defined as small myocytes (diameter &lt; 10 µ) with nuclear positivity to Ki-67 and p-STAT3, positive immunostaining for cytoplasmic alpha-sarcomeric-actin and connexin 43. Their number/mm2, relation with age and pathway of integration were evaluated.

Results
PCR was positive for viral genomes in 16% of cases. NGC mean diameter was 6.6 ± 3.34 vs 22.5 ± 3.11 µm adult cells; their number, in comparable LVEF, was 86.3 ± 10.3/mm2 in patients between 10 and 40 years; 50.4 ±13.8/mm2 in those between 41 and 60; 15.1 ± 5.7/ mm2 in those between 61 and 80; control NGC were 0.2± 0.2/mm2 ; NGC were no statistically different in viral and non-viral myocarditis. HMGB1 and STAT-3 were remarkably higher than controls.
NGC crossed the membrane and grew integrated within the empty necrotic myocytes.

Conclusions
NGCs are constantly recognizable in acute human myocarditis. Their number declines with age. Their integration within necrotic myocytes consents preservation of cardiac structure and function.