bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting CRT outcome by combining markers from personalized ventricular models of electrophysiology and clinical data
Authors: Rokeakh R , Bazhutina A , Khamzin S , Dokuchaev A , Chumarnaya T , Zubarev S , Lyubimtseva T , Lebedeva V , Lebedev D , Solovyova O 
Published: October 2021

Abstract

Introduction
Up to 30% of chronic heart failure (CHF) patients undergoing cardiac resynchronization therapy (CRT) do not respond to the treatment. Low CRT response can be associated with incorrect pacing lead positioning in ventricles and not accounting for individual structural changes in myocardium. Therefore, patient stratification for CRT, operation planning and optimization of CRT device settings remain a challenge.

Purpose
In this study, we develop a predictive model of CRT outcomes based on a combination of clinical data recorded in patients before CRT and on simulations of the response to biventricular pacing in personalized computational models of the ventricles.

Methods
We used retrospective data from 27 CHF patients who underwent CRT device implantation. CRT responders were defined using clinical data in a year after therapy as showing a decrease in the end-systolic volume of the left ventricle (LV) and an increase in the ejection fraction. For each patient, an anatomical model of the heart and torso was reconstructed from CT images and used to compute ventricular activation and ECGs without pacing and under bi-ventricular pacing with various locations of stimulating leads. For building a predictive model of patient response to CRT, we used clinical data before CRT (12 features in total per patient) together with model-derived biomarkers under biventricular pacing with clinical lead position (16 features in total per a model). Using nested stratified cross-validation, logistic regression models were fitted to various combinations of datasets.

Results
The best classifier using a complete set of clinical and simulation data showed an average accuracy = 0.78, ROC AUC = 0.78, sensitivity = 0.75, specificity = 0.8, that were much higher than in the model built on the clinical data only. When the best model was fitted to all data on biventricular pacing with clinical lead position, all ten clinical non-responders were truly classified by the model (Fig. 1, left). Using simulations with optimal lead location as input data for this model, seven out of the ten patients were predicted as responders (Fig. 1, right). Blue and orange colours indicate clinical responders and non-responders. Red circles and numbers mark some clinical non-responding patients that are predicted as responders using optimal TAT values.

Conclusion
Our pilot results show that combination of clinical and simulation data significantly increases the accuracy of classification models for CRT outcomes. Our results suggest that model predictions on the optimal ventricular lead location may essentially increase the probability of CRT success.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Russian Science Foundation Figure 1
Conduction system pacing in cardiac resynchronization: short-mid term follow-up
Authors: Marcantoni L , Pastore G , Baracca E , Pellegrini N , Bartolomei M , Andreaggi S , Galuppi E , Centioni M , Rigatelli G , Roncon L , Zanon F 
Published: October 2021

Abstract

Background
Conduction system pacing (CSP) includes both His Bundle Pacing (HBP) and left bundle branch pacing (LBBP). It engages the conduction system ensuring synchronous activation of ventricles, potentially acting as cardiac resynchronization.

Purpose
The aim of the study is to report technical and clinical outcomes of CSP (HBP or LBBP) utilized in patients referred for cardiac resynchronization therapy.

Methods
CSP was applied in 51 patients (mean age 75±9 years; 47 males) referred for cardiac resynchronization therapy. 41 cases were de-novo implant and 10 were up-grading after PICM. Ischemic aetiology was present in 23 (45%) patients, hypertension in 31 (61%); diabetes in 19 (37%), severe kidney disease in 4 (8%). Devices were checked 48 hours and 1 month after implant and then remotely. Clinical, echocardiographic, electrocardiographic data were also collected.

Results
Conduction system pacing was successfully obtained in 45 (88.3%) patients. In 28 (62%) cases the lead was implanted in the His Bundle and in 17 (38%) in the left bundle. In 6 (11.7%) patients it was not possible to fix the lead in the His Bundle neither in the Left bundle, in these cases a standard quadripolar lead in the coronary sinus was implanted. In 28 (62%) patients was utilized the 3830 4 Fr lumen-less lead and in the remaining 17 (38%) cases a standard stylet-driven lead. Basal mean EF was 33±9% and improved to 42±9% (P&lt;0.005) after a mean follow-up of 266±212 days. Baseline QRSd narrowed from 168±35 ms to135±12 ms. Four (8.8%) patients were hospitalized due to HF symptoms (in 2 cases fast AF was recorded and treated with AV nodal ablation, in 2 cases significant mitral regurgitation).

Conclusions
Conduction system pacing can act effectively as cardiac resynchronization in patients with severe cardiac disfunction and bundle branch block with high success rate, significantly narrowed QRS and improved EF at short-medium term follow-up.

Funding Acknowledgement
Type of funding sources: None. Case report: CRT-D including LB lead
Incidental finding of ”ghost” on echocardiography after transvenous lead extraction among systemic infection patients
Authors: Azari A , Kristjansdottir I , Gadler F 
Published: October 2021

Abstract

Background
Ghosts are described as cylindrical and oscillating structures diagnosed after transvenous lead extraction (TLE) and may consist of thrombi, vegetations and fibrous sheaths. Presence of ghosts is found to be associated with poor outcomes.

Purpose
The aim of this study was to estimate the proportion of patients with ghosts and to describe the characteristic features of `'ghosts” seen post-TLE in a retrospective series of systemic infection patients.

Methods
Medical journals including echocardiography studies of systemic infection patients undergoing TLE between January 1, 2010 and December 31, 2018 were analysed.

Results
A total of 258 patients (72% males, mean age 71±12 years), underwent TLE due to systemic infection. Staphylococcus aureus was the dominant microorganism isolated in blood cultures (40%). Echocardiography identified ghosts as incidental findings in 15 (6%) patients, 1–23 day(s) (median, 5; mean, 7±6 days) post-TLE and ghosts remained up to 51 days post-TLE. Ghosts were described as tubular, echodense and mobile tissues with variety of dimensions (2–50 mm) on echocardiography, mostly localised in right atrium (40%). Ghosts were visually described by surgeons as vegetations on tricuspid valve, organised thrombotic material in superior/inferior vena cavae and more loose thrombotic materials in right atrium in 2 patients who underwent open heart surgery after TLE. Echocardiography could not certainly differentiate between non-infectious tissue and infectious vegetations, thereby endocarditis treatment was prolonged to at least 12 days (mean, 29±14 days) post-TLE in the ghost group.

Conclusion
Although this was a retrospective analysis and ghosts were incidental findings rather than differential diagnosis, which may have underestimated the proportion ghosts identified, ghosts were relatively common in this cohort. Presence of ghosts caused management challenges for clinicians. There is a great need for large multicentre studies enabling establishment of guidelines for diagnosis and management of this common post-TLE finding.

Funding Acknowledgement
Type of funding sources: None. Table 1Figure 1
Labile iron derived from autophagy-mediated ferritin degradation in cardiomyocytes under pressure overload increases myocardial oxidative stress and develops heart failure in mice
Authors: Omiya S , Ito J , Otsu K 
Published: October 2021

Abstract

Introduction
Heart failure is the leading cause of morbidity and mortality in developed countries, and abnormal iron metabolism is common in patients with heart failure. While iron is essential for metabolic homeostasis, it can increase oxidative stress, such as lipid peroxidation resulting from the generation of harmful reactive hydroxyl radicals through the Fenton reaction. Iron is stored in ferritin, which consists of ferritin heavy (FTH1) and light chains. FTH1 has ferroxidase activity and sequestrates labile ferrous iron. Its protein expression is mediated through nuclear receptor coactivator 4 (NCOA4)-mediated autophagic degradation, known as ferritinophagy. However, the role of ferritinophagy in the stressed heart remains unclear.

Methods
Cardiomyocyte-specific NCOA4-deficient (KO) mice were generated and subjected to pressure overload by transverse aortic constriction to induce heart failure. Cardiac remodelling was assessed by echocardiography and histological and molecular analyses four weeks after the operation. Furthermore, lipid peroxidation was inhibited by its potent inhibitor, ferrostatin-1.

Results
Deletion of NCOA4 in mouse hearts did not affect cardiac phenotypes and FTH1 protein level at baseline but improved cardiac systolic function (Fractional shortening, control littermates 21.9% vs KO 45.9%) accompanied by the attenuation of ferritin degradation (The protein level of FTH1, controls 42.9% vs. KO 67.2% of sham-operated hearts) 4 weeks after pressure overload compared to the control littermates. The number of LC3B (a marker of an autophagosome)- and FTH1-positive dots (controls 2.64/103μm2 vs KO 0.30/103μm2) and that of LAMP2a (a marker of a lysosome)- and FTH1-positive dots (controls 3.68/103μm2 vs KO 1.77/103μm2) increased in TAC-operated control hearts, which was attenuated in TAC-operated NCOA4-deficient hearts. The ratio of ferrous iron to the FTH1 protein level, which represents the non-binding fraction of labile ferrous iron to FTH1, was higher in TAC-operated control hearts than in the sham-operated controls and TAC-operated NCOA4–deficient hearts. Although pressure overload increased the level of malondialdehyde, a marker for lipid peroxidation in control hearts, its level was reduced by deletion of NCOA4 (controls 1.12 nmol/mg vs KO 0.68 nmol/mg). Ferrostatin-1 significantly mitigated the development of pressure overload-induced dilated cardiomyopathy in wild-type mice (Fractional shortening, saline 21.4% vs ferrostatin-1 41.7%).

Conclusions
Pressure overload-induced ferritinophagy in cardiomyocytes increases myocardial labile iron pool and oxidative stress resulting in the development of heart failure in mice.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): British heart foundation
Left ventricular end-diastolic pressure predicts in-hospital outcomes in Takotsubo syndrome
Authors: Montone R.A , Del Buono M , Meucci M.C , La Vecchia G , Camilli M , Pedicino D , Trani C , Sanna T , Niccoli G , Crea F 
Published: October 2021

Abstract

Background
Takotsubo syndrome (TTS) is an acute and reversible form of myocardial injury often preceded by an emotional or physical stressful event. Of importance, TTS may be associated to serious adverse in-hospital complications. Coronary angiography and left ventricle angiography remain a cornerstone for TTS diagnosis. However, the prognostic role of invasively assessed left ventricular end-diastolic pressure (LVEDP) at the time of cardiac catheterization has never been investigated.

Purpose
We evaluated the role of invasively assessed LVEDP for predicting in-hospital complications in TTS patients compared to the most widely used echocardiographic parameters of ventricular function.

Methods
We prospectively enrolled 130 patients (mean age 71.2±11.3 years, 114 [87.7%] female) with TTS. Invasive measurement of LVEDP was performed at the time of cardiac catheterization. The rate of in-hospital complications (composite of acute heart failure, cardiogenic shock, life-threatening arrhythmias and all-cause death) was examined.

Results
In-hospital complications occurred in 37 (28.5%) patients. Patients who experienced in-hospital complications had a higher prevalence of neurological trigger and lower prevalence of emotional trigger, higher LVEDP and mean E/e' ratio and lower LV ejection fraction (LVEF) values compared to those who did not experience in-hospital complications. At multivariable Cox regression, higher LVEDP (hazard ratio [HR] 1.12, 95% confidence interval [CI] [1.05–1.20], p&lt;0.001) and lower LVEF (HR 0.95, 95% CI [0.91–0.99], p=0.011) remained independently predictors of in-hospital complications, while emotional trigger was associated to a lower risk (HR 0.24, 95% CI [0.06–0.96], p=0.044). The area under the curve (AUC) for LEVDP in the prediction of in-hospital events was 0.776 (95% CI [0.69–0.86], p&lt;0.001, with a sensitivity and specificity of 95% and 58% using a LVEDP cut-off value of 22.5 mmHg). The AUC was significantly higher for LVEDP than for E/e' ratio (p=0.045).

Conclusions
LVEDP measured at the time of cardiac catheterization may help in identifying TTS patients at higher risk of cardiovascular events during the hospitalization with relevant therapeutic implications. Of note, in the prediction of in-hospital events the LEVDP performed better than non-invasive indexes commonly used for the assessment of diastolic function.

Funding Acknowledgement
Type of funding sources: None.
Clinical impact of pulmonary artery to aorta diameter ratio on left ventricular reverse remodeling in patients with dilated cardiomyopathy
Authors: Shibata N , Hiraiwa H , Kazama S , Kimura Y , Araki T , Mizutani T , Oishi H , Kuwayama T , Kondo T , Morimoto R , Okumura T , Murohara T 
Published: October 2021

Abstract

Background
Left ventricular reverse remodeling (LVRR) is an important predictor for a good prognosis in patients with dilated cardiomyopathy (DCM). Previous reports indicated the pulmonary artery diameter (PAD) to ascending aortic diameter (AoD) ratio as a predictor of adverse outcomes in heart failure patients. However, the impact of the PAD/AoD ratio for predicting LVRR in patients with DCM is unknown.

Aim
The aim of this study is to investigate the association between PAD/AoD ratio and LVRR in patients with DCM.

Methods
From a prospective study, clinically stable DCM patients who were investigated the LVRR on echocardiography and underwent CT at baseline were enrolled. LVRR is defined as left ventricular (LV) ejection fraction increase of 10% and a decrease in indexed LV end-diastolic diameter of 10% compared to those at baseline. PAD and AoD data was collected with nonenhanced computed tomography images at baseline.

Results
In sixty-nine patients (mean age 50.0±13.3 years), the mean LV ejection fraction was 29.8%, and mean LV end-diastolic dimension was 64.5mm, and both of which data was no significant difference between patients with or without LVRR. LVRR was observed in 23 (33.3%) patients. The PAD/AoD ratio was significantly lower in patients with LVRR than without LVRR (81.4% vs. 92.4%, p=0.003). By ROC analysis, the best cut-off for the detection of LVRR was found for a PAD/AoD ratio of 0.9. From multivariate analyses, PAD/AoD ratio was identified as a significant predictor of LVRR. After a median follow-up duration of 2.5 years, the DCM patients with PAD/AoD≥0.9 revealed a significant higher cardiac event than those with PAD/AoD&lt;0.9 (log-rank, p=0.007)

Conclusions
The PAD/AoD ratio is useful for predicting LVRR in patients with DCM. The DCM patients with high PAD/AoD ratio had a poor long-term outcome.

Funding Acknowledgement
Type of funding sources: None. ROC curve for LVRR predictionKaplan-Meier survival curves
Prognostic significance of epicardial adipose tissue in heart failure with preserved and reduced ejection fraction
Authors: Pugliese N.R , De Biase N , Mazzola M , Paneni F , Del Punta L , Gargani L , Mengozzi A , Virdis A , Nesti L , Taddei S , Flammer A , Borlaug B.A , Ruschitzka F , Masi S 
Published: October 2021

Abstract

Background
Increased epicardial adipose tissue (EAT) thickness correlates with metabolic syndrome, insulin resistance, microvascular dysfunction and enhanced pericardial restraint.

Purpose
We measured echocardiographic EAT thickness in heart failure (HF) patients with reduced (HFrEF) or preserved (HFpEF) ejection fraction to determine whether EAT could bear prognostic significance at clinical follow-up.

Methods
We prospectively enrolled 393 consecutive HF outpatients (205 HFrEF, 188 HFpEF) referred to our hospital due to dyspnoea and/or effort intolerance. We performed a resting clinical and biohumoral evaluation, followed by combined cardiopulmonary-echocardiography exercise stress. A composite of cardiovascular death and HF-related hospitalization was chosen as endpoint during follow-up.

Results
Patients with HFpEF displayed higher EAT thickness (median 8 mm, interquartile range [IQR] 4–12 mm) than HFrEF (median 3 mm, IQR 2–6 mm; p&lt;0.0001). During a median follow-up of 20.9 months (IQR 15–25 months), we reported 34 cardiovascular deaths and 146 HF hospitalizations, with no significant differences between the two HF subsets. EAT predicted adverse events independently from body mass index and well-established markers of poor prognosis (e.g., NT-proBNP, peak oxygen consumption). The risk of adverse events increased with increasing EAT thickness in HFpEF and with EAT thinning in HFrEF. Kaplan-Meier analyses for the composite endpoint showed that in HFpEF, the survival probability was significantly lower in patients with thicker EAT than those with thinner EAT. In HFrEF, conversely, patients with thicker EAT had a higher survival probability than those with reduced EAT thickness (Figure 1).

Conclusion
EAT accumulation is more marked in HFpEF than HFrEF and carries different prognostic meanings in the two subsets. In HFpEF, EAT thickening portends adverse outcome, which may be due to increased mechanical restraint and secretion of pro-inflammatory and pro-atherogenic adipokines. In HFrEF, greater EAT thickness seems to have a protective role, while EAT thinning is associated with a worse prognosis, likely reflecting a catabolic state (i.e. cardiac cachexia). Larger studies will clarify whether EAT is a bystander or an active player in the different HF phenotypes.

Funding Acknowledgement
Type of funding sources: None. Figure 1
Current use of NT-proBNP in elderly patients and the impact of the selected threshold value: lessons from a big data analysis
Authors: Meune C , Goudot F.X , Boukertouta T , Lazureanu A , Msadek S , Chenevier-Gobeaux C , Martins-Meune E 
Published: October 2021

Abstract

Background
Natriuretic peptides (NPs) are widely used in the diagnosis and risk stratification of heart failure (HF).NPs may have a reduced discriminative ability in the subgroup of elderly patients.

Methods
We examined all biological tests performed from February 2010 to August 2015 in two districts in the French Brittany. We report the “real-world” use of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in an elderly population and examine the measured concentration and potential impact of the cut-off value's selection.

Results
From a total of 3,606,432 tests ordered in 557,650 adult patients, 56,653 included at least one NT-proBNP measurement. NT-proBNP measurements gradually increased by 10-y age categories up to 80–90 y, and 39,828 (70.3%) of all measurements have been done in patients ≥75y. NT-proBNP concentrations increased with advanced age (Pearson's correlation coefficient: 0.2; p&lt;10–5), with concentrations of 3,564±6,440 ng/L in patients ≥75y. NT-proBNP was inversely correlated with creatinine clearance (p&lt;10–5). Respective proportions of NT-proBNP below the threshold value were 22.6% in patients aged 70 to 80y and less than 10% in those over 80 y when considering a single threshold value of 125 ng/L, and 31% and 33% in the same groups when considering a dual age-adjusted threshold value of 450 ng/L in patients &gt;75y (p&lt;0.001 for all comparisons).

Conclusion
Among a very large cohort, we observed that NT-proBNP is increasingly measured in elderly patients. NT-proBNP concentrations increase with age, and the selection of the threshold value markedly impacts the proportion of “low” versus “high” results.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): Roche Diagnostics Proportion (in %) of low NT-proBNP
Proteomic profiling for detection of early-stage heart failure in the community
Authors: Cauwenberghs N , Sabovcik F , Haddad F , Kuznetsova T 
Published: October 2021

Abstract

Background and purpose
Biomarkers may provide insight into the molecular mechanisms underlying cardiac remodelling and dysfunction. Using a targeted proteomic approach, we aimed to identify circulating biomarkers associated with early-stage heart failure and extract a proteome-based risk classifier for this condition.

Methods
575 community-based participants (mean age, 57 years; 51.7% women) underwent echocardiography and proteomic profiling (CVD II panel, Olink Proteomics). We applied partial least squares-discriminant analysis (PLS-DA) and a machine learning algorithm (extreme gradient boosting, XGBoost) to identify key proteins associated with echocardiographic abnormalities. We used Gaussian Mixture modelling for unbiased clustering to construct phenogroups based on influential proteins in PLS-DA and XGBoost.

Results
Of 87 proteins, 13 were important in PLS-DA and XGBoost modelling for detection of left ventricular (LV) remodelling, LV diastolic dysfunction and/or left atrial reservoir dysfunction: placenta growth factor, kidney injury molecule-1, prostasin, angiotensin-converting enzyme-2, galectin-9, cathepsin L1, matrix metalloproteinase-7, TNFR superfamily members 10A, 10B and 11A, interleukins-6 and 16 and alpha-1-microglobulin/bikunin precursor. Based on these proteins, the clustering algorithm divided the cohort into two distinct phenogroups, with each cluster grouping individuals with a similar protein profile. Participants belonging to the second cluster (n=118) were characterized by an unfavourable cardiovascular risk profile and adverse cardiac structure and function. The adjusted risk of presenting cardiac maladaptation was higher in this phenogroup than in the other cluster (P&lt;0.0001).

Conclusion
We identified proteins reflecting renal function, extracellular matrix remodelling, angiogenesis and inflammation to be associated with echocardiographic signs of early-stage heart failure. Focused proteomic phenomapping discriminated individuals at high risk for cardiac maladaptation in the community.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Research Foundation Flanders