bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transvenous removal of pacing and ICD leads: single Italian referral center experience
Authors: Segreti L , Fiorentini F , Giannotti Santoro M , Barletta V , Di Cori A , Viani S , De Lucia R , Grifoni G , Paperini L , Soldati E , Cellamaro T , Carluccio M , Branchitta G , Zucchelli G , Bongiorni M G 
Published: October 2022

Abstract

Introduction
Device related complications are rising the need of Transvenous Lead Removal (TLR). Transvenous extraction of Pacing (PL) and Defibrillating Leads (DL) is a highly effective technique. Aim of this report is to analyse the longstanding experience performed in a single Italian Referral Center.

Methods
From January 1997 to December 2021, we managed 2925 consecutive patients (2220 men, mean age 65.3 years) with 5370 leads (mean dwell time 74.0 months, range 1–576). PL were 4209 (1903 ventricular, 1801 atrial, 505 coronary sinus leads), DL were 1161 (1140 ventricular, 6 atrial, 15 superior vena cava leads). Indications to TLR were infection in 78% (systemic 27%, local 51%) of leads. We performed mechanical dilatation using a single polypropylene sheath technique and, if necessary, other intravascular tools; we performed an approach through the Internal Jugular Vein (JA) in case of free-floating leads or failure of the standard approach.

Results
We attempted removal in 5359 leads because the technique was not applicable in 11 PL. Among these, 5223 leads were completely removed (97.4%), 51 (1.0%) were partially removed, 85 (1.6%) were not removed. Among 5271 exposed leads: manual traction removed 879 (16.7%) leads; mechanical dilatation using the venous entry site removed 3860 (73.2%) leads; femoral approach (FA) removed 50 (0.9%) leads; and JA removed 346 (6.6%) leads. All the free-floating leads were completely removed, 26.1% by FA and 73.9% by JA. Major complications occurred in 23 cases (0.78%): cardiac tamponade (21 cases, 5 deaths), hemothorax (2 cases, 1 death).

Conclusions
Our experience shows that in centers with wide experience, TLR using single sheath mechanical dilatation has a high success rate and a very low incidence of serious complications. TLR through the Internal Jugular Vein increases the effectiveness and safety of the procedure also in case of free-floating or challenging leads.

Funding Acknowledgement
Type of funding sources: None.
Risk of lead explantation after first-time implantation of cardiac implantable electronic device as a function of comorbidity: a nationwide study
Authors: Alhakak A , Philbert B T , Risum N , Mogensen U M , Jons C , Jacobsen P K , Haarbo J , Johansen J B , Nielsen J C , Riahi S , Torp-Pedersen C , Fosbol E L , Kober L , Vinther M , Weeke P E 
Published: October 2022

Abstract

Background
The benefit of cardiac implantable electronic devices (CIEDs) is challenged by the risk of procedure-related complications and lead explantation. Whether patient comorbidity burden is associated with risk of lead explantation &lt;6 months of implantation is unknown.

Purpose
We assessed the risk of lead explantation and its association with comorbidity burden within 6 months after first-time CIED implantation.

Methods
The study population comprised patients ≥18 years old with first-time CIED implantation (i.e., pacemaker [PM], implantable cardioverter defibrillator [ICD], and cardiac resynchronisation therapy with defibrillator [CRT-D] or without [CRT-P]) using Danish nationwide registries including the Danish Pacemaker and ICD registry (1 January 2000 to 30 June 2018). Patients were followed from their first-time CIED implantation and 6 months forward. Patient comorbidity burden was categorised in four groups according to the Charlson Comorbidity Index (CCI) score: 0 (none), 1–2 (mild), 3–4 (moderate), and ≥5 (severe). Multivariable cause-specific Cox regression was performed to assess risk of lead explantation according to comorbidity burden, with death as competing risk. Comorbidity burden was adjusted for sex, age, type of CIED, and body mass index categories.

Results
We identified 73,491 patients with first-time CIED implantation including 55,733 (75.8%) with PM, 11,351 (15.5%) with ICD, 2,989 (4.1%) with CRT-P, and 3,418 (4.7%) with CRT-D. In total, 1,049 (1.4%) patients underwent lead explantation. The median age of the study population was 75.1 years [25th-75th percentile 66.2–82.5 years], and 62.1% were male. Patients undergoing lead explantation had higher median CCI score, compared with those not undergoing lead explantation (2 [1–3] and 1 [0–3], respectively). The median age and distribution of sex were similar in both groups. In the multivariable Cox regression model (Figure 1), an increase in patient comorbidity burden was associated with higher hazard ratio [HR] of lead explantation, compared with CCI score 0 (CCI score 1–2: HR=1.38 [95% confidence interval [CI]: 1.12–1.69], CCI score 3–4: HR=1.61 [95% CI: 1.28–2.03], and CCI score ≥5: HR=1.60 [95% CI: 1.25–2.05]).

Conclusion
Risk of lead explantation within 6 months after first-time implantation of cardiac implantable electronic device was 1.4% and associated with higher comorbidity burden.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): Independent Research Fund Denmark
The impact of ventricular-arterial coupling on aerobic capacity across the heart failure spectrum
Authors: Pugliese N R , Balletti A , Armenia S , De Biase N , Faita F , Mengozzi A , Paneni F , Ruschitzka F , Virdis A , Ghiadoni L , Taddei S , Williams B , Antonini-Canterin F , Masi S 
Published: October 2022

Abstract

Background
Ventricular-arterial coupling (VAC) can be evaluated as the ratio between arterial stiffness (pulse wave velocity, PWV) and myocardial deformation (global longitudinal strain, GLS).

Objectives
To evaluate VAC across the spectrum of heart failure (HF).

Methods
We introduced a Doppler-derived, single-beat technique to estimate aortic arch PWV (aa-PWV) in addition to tonometry-derived carotid-femoral PWV (cf-PWV). We measured PWVs and 3D-GLS in 155 healthy controls, 75 subjects at risk of developing HF (American College of Cardiology/American Heart Association Stage A-B) and 236 patients in HF Stage C with preserved (HFpEF, n=104) or reduced ejection fraction (HFrEF, n=132). We evaluated peak oxygen consumption (VO2) and peripheral extraction (AVO2diff) using combined cardiopulmonary-echocardiography exercise stress.

Results
aa-PWV was obtainable in all subjects and significantly lower than cf-PWV in all subgroups (p&lt;0.01). PWVs were directly related and increased with age (all p&lt;0.0001). cf-PWV/3D-GLS was similarly compromised in HFrEF (1.08±0.36) and HFpEF (1.05±0.22), while aa-PWV/3D-GLS was more impaired in HFpEF (0.69±0.11) than HFrEF (0.60±0.15; p&lt;0.01). Stage A-B had values of cf-PWV/3D-GLS and aa-PWV/3D-GLS (0.66±0.25 and 0.47±0.12) higher than controls (0.47±0.10 and 0.40±0.10) but lower than Stage C (all p&lt;0.01). Peak AVO2diff was inversely related with cf-PWV/3D-GLS and aa-PWV/3D-GLS (all p&lt;0.01). cf-PWV/3D-GLS and aa-PWV/3D-GLS independently predicted peak VO2 in the overall population (adjusted R2=0.32 and 0.35; all p&lt;0.0001) but only aa-PWV/3D-GLS was independently associated with flow reserve during exercise (R2=0.51; p&lt;0.0001).

Conclusion
Abnormal VAC is directly correlated with greater severity of HF and worse functional capacity. HFpEF shows a worse VAC than HFrEF when expressed by aa-PWV/3D-GLS.

Funding Acknowledgement
Type of funding sources: None.
Biomarker profiles and pathophysiological pathways in patients with chronic heart failure and metabolic syndrome
Authors: Van Der Hoef C C S , Boorsma E M , Emmens J E , Mordi I R , Dihoum A , Lang C C , Voors A A 
Published: October 2022

Abstract

Introduction
The risk factors that collectively define metabolic syndrome (MetS) are common in heart failure (HF) patients. More research is needed to elucidate the individual role of MetS in the pathophysiology of HF.

Purpose
The study investigates the differences in biomarker profiles of HF patients with MetS and without MetS.

Methods and results
The prevalence of MetS was 468 of the 1103 patients (42.4%) in the index cohort and 615 of 1433 (42.9%) patients in the validation cohort. With a microarray analysis of 363 biomarkers, the biomarker profiles of HF patients with versus without MetS were identified. The resulting biomarker profiles were used in network analysis to analyse the underlying pathophysiological mechanisms. The biomarker profile for MetS showed 43 upregulated and 5 downregulated biomarkers in the index cohort. In the validation cohort, there were 58 upregulated and 3 downregulated biomarkers. The most significantly upregulated biomarkers shared between the two cohorts were leptin, fatty acid-binding protein 4, interleukin-1 receptor antagonist, tumour necrosis factor receptor superfamily member 11a, and RET proto-oncogene. Network analysis identified 10 pathways in the index cohort and 6 in the validation cohort, all related to inflammation.

Conclusion
Pathophysiological pathways leading to HF in patients with MetS are most likely related to obesity and the chronic inflammatory state found in these patients. The role of obesity in the pathophysiology of HF should be validated in similar research to analyse and compare the outcomes. Several individual proteins were identified that might be interesting targets for future research and new treatment options for HF patients.

Funding Acknowledgement
Type of funding sources: None.
Overexpression of VEGF-B alters cardiac lipid metabolism and predisposes to heart failure
Authors: Tirronen A , Huusko J , Lehtonen M , Hamalainen W , Hokkanen K , Auriola S , Yla-Herttuala S 
Published: October 2022

Abstract

Background
The compensatory phase of left ventricular hypertrophy (LVH) is characterised by sufficient mitochondrial density and energy production, but prolonged stress leads to cardiac decompensation and decreased mitochondrial biogenesis. This results in energy deficiency and compromised contractile ability, eventually leading to heart failure (HF). Vascular endothelial growth factor B (VEGF-B) is a potent inducer of cardiac angiogenesis and LVH, and more recently it has been associated with lipid metabolism and cardiac function. However, its exact role in these processes has remained unresolved.

Purpose
We wanted to elucidate the effects of VEGF-B overexpression on cardiac metabolism and the development of LVH and HF.

Methods
We used mice expressing VEGF-B transgene under cardiac-specific MHCα promoter and induced pressure overload with angiotensin II infusion. We monitored the cardiac function with high-resolution transthoracic echocardiography and performed immunohistochemical analyses to assess the level of cardiac fibrosis. Furthermore, we analyzed cardiac lipid metabolism with non-targeted LC-MS metabolite profiling and performed functional 3H -labelled triolein uptake studies combined with quantitative RT-PCR.

Results
In this study, we show that the cardiac-specific overexpression of VEGF-B leads to increased plasma triglyceride and free fatty acid levels but reduced cardiac lipid accumulation. Non-targeted LC-MS profiling analysis revealed that the level of cardiac glycerolipids and glycerophospholipids were significantly downregulated although changes in cardiac lipid uptake on functional or gene expression level were not detected. To assess how these metabolic changes affect the development of LVH and HF, we subjected MHCα-VEGF-B mice to angiotensin II infusion. Surprisingly, the survival of MHCα-VEGF-B mice dramatically started to decline after four days of angiotensin II infusion and was only 30% at the 14-day time point. Echocardiographic measurements revealed that the MHCα-VEGF-B mice developed severe HF seen as reduced ejection fraction when compared to control mice (32.2% vs. 64.2% respectively), significantly increased LV end-diastolic diameter and LV volume when compared to the controls. VEGF-B overexpression during pressure overload resulted in severe cardiac fibrosis and downregulation of genes responsible for lipid and glucose uptake, metabolic regulation and mitochondrial function indicating severe cardiac energy deficit. Interestingly, a high fat diet feeding prevented the development of HFrEF by 100% and the suppression of all metabolic pathways.

Conclusion
VEGF-B regulates cardiac energy production and the overexpression of VEGF-B results in cardiac energy deficit that during pressure overload leads to HFrEF and severe mortality.

Funding Acknowledgement
Type of funding sources: Public grant(s) – EU funding. Main funding source(s): ERC and H2020
Role of impaired iron transport on exercise performance in heart failure patients
Authors: Lo Russo G , Agostoni P G , Campodonico J , Junod D , Carulli E , Gaudenzi Asinelli M , Doni F , Bonomi A 
Published: October 2022

Abstract

Aims
Impaired iron transport (IIT) occurs frequently in heart failure (HF) patients, even in the absence of anaemia and it is associated with a poor quality of life and prognosis. The impact of IIT on exercise capacity, as assessed by the cardiopulmonary exercise test (CPET), in HF is at present unknown. The aim of this article is to evaluate in HF patients the impact on exercise performance of IIT, defined as transferrin saturation (TSAT) &lt;20%.

Methods and results
We collected data of 676 patients hospitalised for HF. All underwent laboratory analysis, cardiac ultrasound, and CPET. Patients were grouped by the presence/absence of IIT and anaemia (haemoglobin &lt;13 and &lt;12 g/dL in male and female, respectively): Group 1 (G1) no anaemia, no IIT; Group 2 (G2) anaemia, no IIT; Group 3 (G3) no anaemia, IIT; Group 4 (G4) anaemia and IIT. Peak oxygen uptake (peakVO2) reduced from G1 to G3 and from G2 to G4 (G1: 1266±497 mL/min, G2: 1011±385 mL/min, G3: 1041±395 mL/min, G4: 833±241 mL/min), whereas the ventilation to carbon dioxide relationship slope (VE/VCO2 slope) increased (G1: 31.8±7.5, G2: 34.5±7.4, G3: 36.1±10.2, G4: 37.5±8.4). At multivariate regression analysis, peakVO2 independent predictors were anaemia, brain natriuretic peptide (BNP), and left ventricular ejection fraction, whereas VE/VCO2 slope independent predictors were IIT and BNP.

Conclusions
In HF IIT is associated with exercise performance impairment independently from anaemia, and it is a predictor of elevated VE/VCO2 slope, a pivotal index of HF prognosis.

Funding Acknowledgement
Type of funding sources: Private hospital(s). Main funding source(s): Centro cardiologico Monzino, Italy
Low-dose dopamine improves ventilatory efficiency during exercise in heart failure with preserved ejection fraction through inhibition of tonic activity of peripheral chemoreceptors
Authors: Kulej-Lyko K , Niewinski P , Tubek S , Ponikowski P 
Published: October 2022

Abstract

Introduction
Peripheral chemoreceptors (PChRs) play an important role in adequate oxygenation by 1) maintaining baseline ventilation (tonic activity) and 2) providing hyperventilation in response to acute hypoxia (reflexia). It has been previously shown that in patients with heart failure with reduced ejection fraction hypertonicity and/or hyperreflexia of PChRs contribute to exercise intolerance (ExIn). It is unknown whether similar mechanisms are present in heart failure with preserved ejection fraction (HFpEF) and which component of PChR functionality has a decisive role in this matter.

Purpose
The aim of this study was to evaluate the role of PChRs in ExIn in patients with HFpEF.

Methods
All patients underwent assessment of PChRs which included measurements of: 1) tonic activity (TA, decrease in ventilation following pharmacological inhibition of PChRs), 2) reflex response (RR; an increase in ventilation in the response to acute hypoxia). The inhibition of PChRs was achieved with low-dose dopamine infusion (3 μg kg–1 min–1) and the acute hypoxia was produced with brief nitrogen gas administrations. Enrolled patients underwent symptom-limited cardiopulmonary exercise test using cycle ergometer from which peak oxygen consumption (peakVO2) and the slope relating ventilation to carbon dioxide (VE/VCO2 slope) were derived. All measurements (including PChRs' function tests and cardiopulmonary exercise test) were performed twice in a randomized, double-blinded and placebo-controlled manner (dopamine vs normal saline).

Results
We included 12 stable patients with HFpEF (age: 73±7 years, LVEF: 58±3%). During exercise the inhibition of PChRs with dopamine resulted in the improvement (decrease) in VE/VCO2 slope comparing to placebo (36±3.6 vs 34.3±3.7, p=0.04) but no change regarding peakVO2. There was a correlation between TA and relative magnitude of improvement in VE/VCO2 following PChRs inhibition (R=0.76, p=0.005). We also found a trend for correlation between RR and VE/VCO2 measured during placebo (R=0.56, p=0.059). There was no correlation between TA and RR (p=0.24).

Conclusion
Both TA and RR of PChRs are involved in ventilatory inefficacy during exercise in HFpEF – but in different ways. While augmented RR is likely an indicator of high VE/VCO2, the elevated TA indicates the magnitude of the improvement in exercise tolerance following PChRs deactivation. Thus, further interventions aimed at the modulation of PChRs should enroll patients based on TA rather than RR.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Science Centre, PRELUDIUM grant
Myeloperoxidase as therapeutic target in HFpEF
Authors: Lejeune S , Ginion A , Menghoum N , Horman S , Beauloye C , Pouleur A C 
Published: October 2022

Abstract

Background
Inflammation and oxidative stress are thought to play an important role in the pathophysiology of HFpEF through the development of endothelial dysfunction. Myeloperoxidase (MPO), a leukocyte-derived enzyme, functions as a link between oxidative stress and inflammation and is an interesting therapeutic target.

Purpose
To compare MPO levels between HFpEF and old controls and to define clinical characteristics associated with high levels of MPO.

Methods
Patients with HFpEF (N=55) and controls &gt;60 years (N=18) were prospectively included. All subjects underwent complete echocardiography and standard biology. MPO levels were dosed by ELISA assay. Endothelial function was assessed by peripheral arterial tonometry through the reactive hyperemia index (RHI). Characteristics were compared using independent samples t-test or chi square test.

Results
Patients with HFpEF (80±8.5 years, 65% female) had higher levels of myeloperoxidase compared to controls (74±6.2 years, 72% female) (34.7 ng/mL [22.7; 43.9] versus 22.5 [18.1; 31.9], p=0.026) (Figure 1). HFpEF patients with levels of MPO above the median were more often men and diabetic and had higher levels of NTproBNP and CRP. However, MPO levels were not associated with endothelial function measured by RHI (Table 1).

Conclusion(s)
HFpEF patients have higher levels of myeloperoxidase than control subjects, reflecting leukocyte activation and oxidative stress. Myeloperoxidase levels are associated with inflammation and disease severity. Myeloperoxidase inhibitors could be useful for the treatment of HFpEF patients, especially in the subgroup of patients with diabetes.

Funding Acknowledgement
Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Fondation Damman
The adverse effects of the respiratory effort on the pulmonary circulation are independent of the ejection fraction and heart failure etiology
Authors: Markovitch N , Rispler S , Feld Y , Solomonica A , Yalonetsky S , Musallamis A , Kerner A , Roguin A , Landesberg A 
Published: October 2022

Abstract

Introduction
Heart failure (HF) is associated with hemodynamic lung congestion that leads to dyspnea and excessive respiratory effort.

Purpose
We hypothesized that this HF induced excessive respiratory effort adversely affects both ventricles loading conditions, leading to a vicious cardiopulmonary cycle and progressive cardiac deterioration, and that this vicious cardiopulmonary cycle is independent of HF etiology.

Methods
The hemodynamic and respiratory indices were simultaneously measured in patients undergoing right heart catheterization for the diagnosis of dyspnea. The pulmonary wedge pressure (PCWP) is modulated by the changes in the intrathoracic pressure. The latter is determined by the respiratory effort. To quantify the respiratory effort, the PCWP was decomposed into cardiac and respiratory waves. The respiratory effort (Presp) was defined as the peak to peak amplitude of the respiratory wave that modulated the PCWP. The immediate effects of the respiratory effort on the pulmonary capillary wedge pressures (PCWP) were scrutinized by asking the patients to perform intentional vigorous breathing and short apneic events.

Results
The HF patients (N=50) exhibited a high Presp of 9.3±5.0 mmHg, ∼3.5-fold higher than the normal respiratory effort. The baseline end-expiratory PCWP (PCWPee) and end-expiratory pulmonary artery pressure of the HF patients have linear relationship with the baseline Presp with slops of 0.78±0.05 and 1.42±0.09 respectively. The changes in PCWPee appeared immediately, within a single breathing-cycle (t =1.65±0.39 sec) in all patients, when each patient intentionally changed the respiratory effort from apnea to his maximum Presp of 19.8±8.6 mmHg. The PCWP during apnea underestimated the HF severity and yielded lower PCWPee while severe respiratory effort markedly increased the PCWPee. Interestingly, similar slope of the instantaneous relationship between the varying Presp and observed PCWPee was obtained for all the patients, independently of the baseline PCWPee-. The PCWPee rose immediately by 0.43±0.15 for every 1 mmHg of Presp. Similar slope was observed in HF patients with ischemic (N=24) and non-ischemic (N=26, p=0.36) HF diseases (p=0.26), and in those with preserved (N=35) or reduced (N=15) ejection fractions (p=0.91).

Conclusions
The respiratory effort has immediate effects on the hemodynamic congestion and the workloads of the heart, and this adverse effects are independent of HF etiology. The observations support the existence of a vicious cardiopulmonary cycle that can lead to decompensation, where the respiratory effort plays a pivotal role. It may explain the similar prognosis of patients with various ejection fractions and etiologies, but with similar dyspnea severity and clinical symptoms.

Funding Acknowledgement
Type of funding sources: None.