bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictors of major procedure-related complications in transvenous lead extraction
Authors: Doring M , Ebert M , Lucas J , Hindricks G , Richter S 
Published: November 2020

Abstract

Background
Transvenous lead extraction (TLE) has become the mainstay therapy for device-related infections. Though TLE procedures are associated with low complication and high success rates, risk factors for major procedure-related complications remain not well defined.

Purpose
To evaluate the safety and efficacy of TLE in a large single centre cohort and to identify risk factors for major complications.

Methods
All consecutive patients who had undergone TLE in our department between May 2012 and January 2020 were included in a prospective registry. Our protocol for TLE followed a stepwise approach according to lead dwell time and estimated complexity of the procedure: use of simple traction ± locking stylet (LS) ± mechanical and/or powered sheaths ± snare technique. In case of unsuccessful extraction from the venous entry site, femoral or jugular access was approached. Patient characteristics, procedural data and complications were gathered and analysed. Logistic regression analysis was applied to identify risk factors for major procedure-related complications.

Results
A total of 1717 leads (443 [25.9%] ICD leads) were targeted for TLE in 810 patients (67±15 years; 76% male). The mean lead dwell time was 83±60 months. The leading indication for TLE was cardiac device related infection (CDRI) in 527 patients (65.1%), of whom 273 (51.8%) had systemic and 254 (48.2%) localized infection. Two hundred eighty-three patients (34.9%) underwent TLE for non-CDRI causes. Leads were extracted by simple traction in 28.2%, traction with LS in 4.1%, dilator sheaths with LS in 50.1%, and additional use of powered mechanical sheaths in 13.0%. The snare technique was used in 4.6%. Venous access for TLE was exclusively from the entry site in 94.8%, combined from femoral in 4.0% and jugular in 1.2%. TLE was completely successful in 96.2%, partially successful in 2.1%, and failed in 1.7% of all attempted leads, which translated to a clinical success rate of 96.8%.
Eighteen patients (2.2%) experienced minor and 12 patients (1.5%) had major procedure-related complications (cardiac tamponade/perforation) including one intraprocedural death (0.1%) from fulminant pulmonary embolism. Lead-years-per-patient (HR 1.064, 95% CI 1.032–1.096; p&lt;0.001), dwelling time of the oldest lead (HR 1.013, 95% CI 1.007–1.019; p&lt;0.001), and BMI (HR 0.877, 95% CI 0.772–0.997; p=0.020) were significant predictors for major complications in logistic regression analysis.

Conclusion
TLE is feasible, effective and safe in our large single centre experience. Overall complication and failure rates are low. Following our TLE protocol, dwelling time of the extracted leads and low BMI were associated with major procedure-related complications.

Funding Acknowledgement
Type of funding source: None
Impaired high-density lipoprotein function in patients with heart failure
Authors: Emmens J.E , Congzhuo J , Ng L.L , Voors A.A , De Boer R.A , Tietge U.J.F 
Published: November 2020

Abstract

Background
We recently showed that a lower high-density lipoprotein cholesterol (HDL-C) concentration was one of the strongest predictors of death or heart failure (HF) hospitalisation in patients with HF. In a follow-up study, we suggested that this association could be partly explained by HDL proteome composition. However, whether the emerging concept of HDL function contributes to prognosis of HF patients has not been addressed.

Methods
We measured three key HDL function metrics, namely cholesterol efflux, antioxidative capacity, and anti-inflammatory capacity, at baseline and after 9 months in 446 randomly selected HF patients from BIOSTAT-CHF. Additionally, the relationship between HDL functionality and HDL proteome composition was determined in 86 patients.

Results
From baseline to 9 months, HDL-C concentrations did not substantially change, but HDL-mediated cholesterol efflux and anti-inflammatory capacity had decreased (both P&lt;0.001). In contrast, antioxidative capacity improved during the 9 months follow-up (P&lt;0.001). Higher HDL-mediated cholesterol efflux was independently associated with lower risk of mortality after adjustment for BIOSTAT risk models and log HDL-C (HR=0.81 [95% CI: 0.71–0.92], P=0.001). Other functionality parameters were not associated with outcome. Several HDL proteins correlated with HDL functionality, mainly with cholesterol efflux, and apolipoprotein A1 emerged as the main protein associated with all three functionality parameters.

Conclusions
HDL-mediated cholesterol efflux and anti-inflammatory capacity significantly decreased over time in patients with HF. Better baseline cholesterol efflux was prospectively associated with reduced mortality during follow-up independent of HDL-C. Combined these data indicate that HDL function measurements have the potential to provide clinical information beyond static HDL-C concentrations in HF patients.
Changes in HDL functionality over time

Funding Acknowledgement
Type of funding source: Public grant(s) – EU funding. Main funding source(s): European Commission
Global differences in heart failure with preserved ejection fraction: the paragon-hf trial
Authors: Tromp J , Clagget B.L , Jhund P , Kober L , Widimsky J , Chopra V , Ge J , Maggioni A.P , Martinez F , Zannad F , Lefkowitz M.P , Shi V.C , McMurray J.J.V , Solomon S.D , Lam C.S.P 
Published: November 2020

Abstract

Background
Heart failure with preserved ejection fraction (HFpEF) is a global public health problem with important regional differences. We investigated these differences in the PARAGON-HF trial, the largest, most inclusive global HFpEF trial.

Methods
We studied differences in clinical characteristics, outcomes and regional treatment effects of Sacubitril/Valsartan in 4796 patients with HFpEF from the PARAGON-HF trial, grouped according to geographic region.

Results
Regional differences in patient characteristics and comorbidities were observed (Figure 1): patients from Western Europe were oldest (75±7 years) with the highest prevalence of atrial fibrillation (36%); Central/Eastern European patients were youngest (71±8 years) with the highest prevalence of coronary artery disease (CAD, 49%); North American patients had the highest prevalence of obesity (64%) with metabolic syndrome; Latin American patients were youngest and had a high prevalence of obesity (53%); Asia-Pacific patients had a high prevalence of diabetes (44%) despite low prevalence of obesity (26%). Rates of the primary composite endpoint of total hospitalizations for HF and death from cardiovascular causes was lowest in patients from Central Europe (9 per 100 patient years) and highest in patients from North America (28 per 100 patient years), which was primarily driven by a greater number of total hospitalizations for HF and independent of confounders. In the total population, sacubitril–valsartan did not result in a significantly lower rate of total hospitalizations for heart failure and death from cardiovascular causes with no significant heterogeneity in treatment response to sacubitril-valsartan across regions.

Conclusion
This first report on regional differences in the largest prospective global trial in HFpEF suggests substantial regional heterogeneity with respect to phenotype, outcomes and quality of life.
Figure 1

Funding Acknowledgement
Type of funding source: Private company. Main funding source(s): Study funded by Novartis
Global constructive work and left atrial reservoir function is reduced in patients with heart failure with preserved ejection fraction compared with patients with preclinical diastolic dysfunction
Authors: Tunyan L.G , Chilingaryan A.L , Adamyan K.G , Zelveyan P.H , Tumasyan L.R , Kzhdryan H.K 
Published: November 2020

Abstract

Heart failure with preserved ejection fraction (HFpEF) remains an unresolved issue with morbidity and mortality comparable with that of reduced EF HF. Diastolic dysfunction (DD) is the hallmark of HFpEF but it is unclear why some patients do not develop symptoms and remain in preclinical DD (PDD) stage with the same degree of DD as patients with HFpEF. We assumed that patients with HFpEF might have more deteriorated global myocardial work (GW) and left atrial reservoir longitudinal strain (LALS) parameters compared with PDD patients.

Methods
210 patients (150 female, mean age 71±5 years) of which 118 with PDD and 92 with HFpEF were enrolled in this study. PDD was diagnosed if patients had normal NT-proBNP values, and at least 3 of the following echocardiographic criteria at rest or after diastolic stress echocardiography: end-systolic left atrial volume index (LAVi) &gt;34 ml/m2, LV E/e' &gt;13, average LV e' &gt;8.5, and systolic pulmonary artery pressure &gt;30 mmHg. GW index (GWI) was obtained from pressure-strain loops composed from speckle tracking analysis indexed to brachial systolic blood pressure, global constructive work (GCW) was measured as the sum of positive work due to myocardial shortening during systole and negative work due to lengthening during isovolumic relaxation, global wasted work (GWW) was calculated as energy loss by myocardial lengthening in systole and shortening in isovolumic relaxation, and GW efficiency (GWE) as the percentage ratio of constructive work to the sum of constructive work and wasted work. LALS was measured by speckle tracking echocardiography as average value of two basal segments in apical 4 chamber view along LAVi and 4D LV mass index (LVMi) offline by experienced echocardiographer who was unaware of the study aims.

Results
Patients with PDD and HFpEF have comparable values of LAVi, LVMi, GWI, GWW, and GWE (LAVi 38.4±3.9 ml/m2 vs 39.1±4.1 ml/m2, p=NS; LVMi 82.8±11.4 g/m2 vs 83.5±10.2 g/m2, p=NS; PDD GWI 2389±154 mmHg% vs 2368±139 mmHg%, p=NS; GWW 62±5 mmHg% vs 65±4 mmHg%, p=NS; GWE PDD 89±9% vs 87±11%, p=NS). LALS and GCW were significantly reduced in patients with HFpEF compared with PDD patients (LALS 21.3±7% vs 29±5%, p&lt;0.01; GCW 1964±112 mmHg% vs 2259±164 mmHg%, p&lt;0.01).

Conclusion
Patients with HFpEF have reduced LALS and GCW compared with PDD patients. Both parameters are indicative for LA and LV myocardial fibrotic burden respectively which might be one of the probable explanations of PDD transition to HFpEF.

Funding Acknowledgement
Type of funding source: Public Institution(s). Main funding source(s): Committee of Science at Ministry of Education of Republic of Armenia
Prognostic value of nutritional status in patients with heart failure with preserved ejection fraction, with and without atrial fibrillation: insights From PURSUIT-HFpEF Registry
Authors: Kawasaki M , Yamada T , Watanabe T , Morita T , Furukawa Y , Tamaki S , Kikuchi A , Kawai T , Seo M , Fukunami M , Yasumura Y , Hayashi T , Yano M , Hikoso S , Sakata Y 
Published: November 2020

Abstract

Background
Malnutrition is one of the most important comorbidities among heart failure (HF) patients, and serum cholinesterase (CHE) has been reported to be a prognostic factor in HF patients. On the other hand, atrial fibrillation (AF) is frequently observed in patients with HF with preserved ejection fraction (HFpEF). However, there is little information available on the prognostic value of nutritional status in HFpEF patients, with and without AF. We sought to clarify the prognostic value of CHE in HFpEF with and without AF and compare it with that of other nutrition indices such as gastric nutritional risk index (GNRI), controlling nutritional status (CONUT), and the prognostic nutritional index (PNI).

Methods and results
Patients data were extracted from The Prospective mUlticenteR obServational stUdy of patIenTs with Heart Failure with Preserved Ejection Fraction (PURSUIT HFpEF) study, which is a prospective multicenter observational registry for acute decompensated heart failure patients with left ventricular ejection fraction ≥50% in Osaka. We analyzed 380 patients (median age: 80 [75–87] years, male: 46%) after exclusion of patients with in-hospital death, missing follow-up data, or missing data to calculate nutritional indices. On admission, 155 patients had AF. Laboratory data were obtained at discharge. During a mean follow up period of 1.1±0.6 years, 131 patients had a composite endpoint (CE) of all-cause death and hospitalization for worsening heart failure or cerebrovascular disorder. In multivariate Cox analysis, in patients with AF, CHE was significantly associated with CE independently of age, gender and body mass index after the adjustment with serum albumin, total cholesterol levels and total lymphocyte count, while it was not significantly associated with CE in patients without AF. C-index of CHE (0.708) was higher than that of GNRI (0.555, p=0.0028), CONUT (0.651, p=0.208) and PNI (0.635, p=0.208) in AF patients, while there were no significant differences in those nutritional indices in patients without AF. Kaplan-Meier curve analysis revealed that AF patients with lower CHE (&lt;208 U/L = median value) had higher risk of CE than those with higher CHE (44% vs 18%, adjusted HR 3.26 95% CI [1.66–6.67], p=0.0005), while there was no significant difference in the occurrence rate of CE between patients with and without higher CHE in non-AF group (42% vs 31%, adjusted HR 1.28 95% CI [0.78–2.13], p=0.33).

Conclusions
Prognostic value of CHE would be stronger than other nutritional indices in HFpEF patients with AF, while it would be weak in HFpEF patients without AF.

Funding Acknowledgement
Type of funding source: Private company. Main funding source(s): Roche Diagnostics K.K.; Fuji Film Toyama Chemical Co. Ltd.
Left ventricular noncompaction in patients with heart failure with preserved ejection fraction characterized by multimodality imaging
Authors: Visoiu I.S , Mihalcea D , Rimbas R.C , Nicula A , Magda L.S , Mihaila-Baldea S , Luchian M.L , Chitroceanu A , Marinescu A.V , Velcea A , Vinereanu D 
Published: November 2020

Abstract

Background
Left ventricular non-compaction (LVNC) is associated with increased risk of heart failure (HF). If LVNC or hyper-trabeculation in HF with preserved ejection fraction (HFpEF) is an adaptive or stand-alone condition that contribute to generation of HF is not clearly understood yet.

Aim
To describe LV functional and structural parameters in HFpEF with LVNC by comparison with HFpEF without LVNC.

Methods
We assessed 42 patients with HFpEF, 21 with LVNC (61±9 yrs) and 21 without LVNC, age and risk factors matched (LVC), by NTproBNP, 2D echocardiography (2DE), speckle-tracking (STE), and cardiac magnetic resonance (CMR) (Figure 1). LVNC diagnosis was based on Petersen and Jacquier criteria, by the NC/C ratio and the percentage of NC myocardium. Two gradients were calculated: a base to apex gradient (LVbase-apex) and an endo-epicardial gradient (LVendo-epi). LV mass, LV end-diastolic volume (LVEDV), and T1 mapping with extracellular volume (ECV) were measured, while mean value of native T1 for apical segments (apicalT1), mean value of ECV for apical (apical ECV), and basal segments (basal ECV), and gradient between them (ECV base-apex) were calculated.

Results
In the LVNC, mean NC/C ratio was 2.9±0.5mm and the percentage of NC myocardium 24.4±8.8%. NTproBNP was higher in LVNC group (294±282 vs. 163±71 pg/ml, p=0.047). Functional findings were consistent with the structural changes from CMR. LVNC patients have higher native T1 in the apical segments (Table). ECV was globally expanded in LVNC compared to LVC (p=0.002) suggesting diffuse fibrosis, but the difference between groups was more relevant for apical ECV (29.6±3.9% vs 25.1±2.8%, p&lt;0.001), with a higher ECV base-apex gradient in LVNC group. ECV base-apex gradient was negatively correlated with the percentage of NC myocardium (p=0.003, R=0.64).

Conclusion
Patients with HFpEF with LVNC have more fibrosis, with more severe changes in the apical segments on CMR than HFpEF without NC. They have also significantly decreased apical deformation, lower base to apex deformation gradient and lower transmural deformation gradient, due to non-compaction itself, which involves the endocardial layer. These findings suggests that NC in HFpEF is an independent condition rather than an adaptive one.
Figure 1

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): Ministry of Research and Innovation, CNCS-UEFISCDI.
Diagnostic usefulness of passive leg raising test for detection of heart failure with preserved ejection fraction compared to cycle ergometer exercise (invasive hemodynamic study)
Authors: Hwang S.J , Kang M.G , Kim K.H , Park H.W , Koh J.S , Park J.R , Hwang J.Y 
Published: November 2020

Abstract

Background
Invasive diastolic stress test using cycle ergometer is gold standard for diagnosis of heart failure with preserved ejection fraction (HFpEF) by demonstrating elevation of left ventricular end diastolic pressure (LVEDP) during exercise. It is well known that passive leg raising increases preload and augments LVEDP in HFpEF patients. However correlation between passive leg raising induced increase of LVEDP and cycle ergometer exercise induced increase of LVEDP is not well established. Therefore we investigated whether passive leg raising test could substitute cycle exercise test for diagnosis of HFpEF.

Method
Forty-five patients with unexplained dyspnea and ejection fraction &gt;50% underwent invasive exercise test. After measuring baseline LVEDP in supine position using pigtail catheter through radial artery approach, LVEDP during passive leg raising was evaluated. Then exercise LVEDP was measured after 3 minutes of 20 watt supine cycle ergometer exercise. Patients with normal resting LVEDP &lt;16mmHg were enrolled. Patients with cycle ergometer exercise LVEDP &gt;26mmHg were classified as HFpEF and exercise LVEDP &lt;26mmHg were defined as noncardiac dyspnea.

Results
Among 45 patients with unexplained dyspnea with preserved EF, 30 patients with ergometer exercise LVEDP &gt;26mmHg were grouped as HFpEF and 15 patients with exercise LVEDP &lt;26mmHg grouped as noncardiac dyspnea (NCD). Resting LVEDP was higher in HFpEF than NCD (14±2mmHg vs 11±3mmHg, P=0.01) but there was substantial overlap (figure 1) showing poor differentiation power of resting LVEDP. Passive leg raising increased LVEDP in both HFpEF and NCD but this was more marked in HFpEF group than in NCD group with minimal overlap (24±4mmHg vs 17±2mmHg, P&lt;0.001) (figure 2). Passive leg raising LVEDP was well correlated with cycle ergometer exercise LVEDP (R2=0.60, P&lt;0.01). The best cutoff value for passive leg raising LVEDP to detect HFpEF was 20mmHg (sensitivity, 0.87; specificity, 1.00), giving an area under the curve of 0.93 (95% confidence interval, 0.80 to 0.99). Positive predictive value of passive leg raising LVEDP &gt;20mmHg for diagnosis of HFpEF was 96% and negative predictive value was 77%.

Conclusion
Passive leg raising induced augmentation of left ventricular end diastolic pressure (LVEDP) was well correlated with cycle exercise induced elevation of LVEDP in HFpEF patients. Passive leg raising test may be used for detecting HFpEF with good accuracy in substitution for cycle ergometer exercise test.

Funding Acknowledgement
Type of funding source: None
Cardioprotective Effects of Kv4.3 on Oxidative Stress in Heart Failure
Authors: Wang Y , Cheng J 
Published: November 2020

Abstract

Background
Oxidative stress is a pathogenic mediator in heart failure (HF) development, causing excessive Ca2+/calmodulin-dependent kinase II (CaMKII) activation and consequent cardiac dysfunction. We previously reported that Ito channel subunit Kv4.3 couples to CaMKII and inhibits Ca2+-induced CaMKII activation. However, whether Kv4.3 also blocks the oxidation-induced CaMKII activation and the impact on cardiac function in failing heart remain undetermined.

Methods and results
Dissociation of Kv4.3 from Kv4.3-CaMKII units by 4-AP incubation or down-regulation of Kv4.3 by transfection with Kv4.3 antisense adenovirus in adult mouse ventricular myocytes enhanced H2O2-induced increase in CaMKII oxidation and autophosphorylation. Co-immunoprecipitation of Kv4.3 with CaMKII, rather than its oxidative or phosphorylated forms, was detected with H2O2 Incubation. Fluorescence spectra assay showed that Kv4.3 binding prevented the transformation of inactive CaMKII to its active conformation in the presence of Ca2+/CaM and H2O2. In pressure-overload HF mice, transfection with Kv4.3 adeno-associated virus (AAV9) had no impact on the content of reactive oxygen species but effectively suppressed CaMKII oxidation and the oxidative CaMKII activation. Importantly, AAV-Kv4.3 transfection led to remarkable improvement in both systolic and diastolic function in failing heart, which is associated with the reduction in ventricular fibrosis, increase in Ca2+ transient and sarcomere shortening in ventricular myocytes with unchanged Ca2+ decline and sarcomere relaxation and preserved myofilament sensitivity to Ca2+.

Conclusion
Our results demonstrated that Kv4.3 is an important endogenous regulator that blocks CaMKII oxidation and oxidation-induced CaMKII activation by binding to CaMKII and preventing Ca2+/CaM-induced conformational change. Restoration of Kv4.3 expression improves both systolic and diastolic function, manifesting a promising strategy for HF therapy.

Funding Acknowledgement
Type of funding source: Foundation. Main funding source(s): National Natural Science Foundation of China (NSFC) and National Institutes of Health (NIH) of America