bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of chronic total coronary occlusion percutaneous coronary intervention on absolute perfusion in remote myocardium
Authors: De Winter R W , Schumacher S P , Van Diemen P A , Jukema R A , Somsen Y B O , Stuijfzand W J , Bom M J , Everaars H , Van Rossum A C , Van De Ven P M , Verouden N J , Danad I , Raijmakers P G , Nap A , Knaapen P 
Published: October 2021

Abstract

Background
Successful revascularization of a chronic total coronary occlusion (CTO) impacts coronary physiology of the remote myocardial territory.

Purpose
This study evaluated the effect of CTO percutaneous coronary intervention (PCI) on changes in absolute perfusion in remote myocardium as assessed by serial [15O]H2O positron emission tomography (PET) perfusion imaging.

Methods
A total of 164 patients underwent [15O]H2O PET imaging at baseline and 3 months after successful single-vessel revascularization of a CTO to evaluate changes in hyperemic myocardial blood flow (hMBF) and coronary flow reserve (CFR) in the remote myocardial territory supplied by both non-target coronary arteries.

Results
Remote hMBF and CFR improved (2.29±0.67 to 2.48±0.75 mL min–1 g–1 and 2.48±0.76 to 2.74±0.85, respectively) after CTO revascularization (p&lt;0.01 for both). Absolute perfusion indices in the CTO vessel and the remote myocardium showed a positive linear correlation, both before (r=0.75, p&lt;0.01 and r=0.77, p&lt;0.01 for hMBF and CFR, respectively) and after (hMBF: r=0.87, p&lt;0.01 and CFR: r=0.81, p&lt;0.01) CTO PCI. Absolute increases in remote myocardial perfusion were largest in patients with a higher increase in hMBF (βeta [β] 0.56; 95% CI: 0.47–0.65; p&lt;0.01) and CFR (β 0.51 (0.42–0.60); p&lt;0.01) in the CTO territory, independent of clinical, angiographic and procedural characteristics. Furthermore, baseline (hMBF: β −0.24 (−0.39, −0.08); p&lt;0.01 and CFR: β −0.26 (−0.41, −0.11); p&lt;0.01) and post-PCI perfusion (hMBF: β 0.36; (0.27, 0.46); p&lt;0.01 and CFR: β 0.30 (0.21, 0.40); p&lt;0.01) in the CTO vessel were independently associated with the increase in remote myocardial perfusion after CTO PCI.

Conclusions
An overall increase in remote myocardial perfusion was observed following CTO PCI. Absolute perfusion indices in the remote myocardium showed a positive linear correlation with perfusion in the CTO vessel, before and after CTO revascularization. Importantly, baseline, post-PCI and the absolute increase in perfusion in the CTO territory were independently associated with increases in remote myocardial perfusion after revascularization.

Funding Acknowledgement
Type of funding sources: None. Figure 1Figure 2
The valve uptake index: a new measure in [18F]FDG PET/CT for the diagnosis of prosthetic valve endocarditis
Authors: Roque A , Pizzi M N , Fernandez-Hidalgo N , Romero-Farina G , Burcet G , Reyes J L , Cuellar-Calabria H , Aguade-Bruix S 
Published: October 2021

Abstract

Background
Diagnosis of PVE by PET/CTA is based on visual and quantitative evaluation of morpho-metabolic features. The FDG uptake pattern is a main diagnostic criterion, but can be visually unclear and susceptible to subjectivity. The valve uptake index (VUI) is a new measure designed to provide a more objective indication of the distribution of metabolic activity.

Purpose
To validate the diagnostic accuracy of the valve uptake index (VUI) (SUVmax-SUVmean)/SUVmax, in patients with suspicion of prosthetic valve endocarditis (PVE). To establish a cut-off value that allows diagnosis of infection. Finally, to determine the incremental value of adding the VUI to the classic parameters for the diagnostis of PVE by PET/CT.

Methods
Retrospective analysis of 122 patients, with a conclusive diagnosis of definite or rejected PVE and who had undergone a cardiac PET/CTA scan. We measured the VUI and recorded the SUVmax, SUVratio, uptake pattern and the presence of endocarditis-related anatomic lesions. The diagnostic accuracy of these parameters was calculated.

Results
The VUI values were 0.54±0.1 vs. 0.36±0.08 in the definite PVE group vs. the rejected group, respectively (mean±SD; p&lt;0.001). A cut-off value of VUI&gt;0.45 showed a sensitivity, specificity and diagnostic accuracy for PVE of 85%, 90.3% and 87.4%, and significantly increased diagnostic ability for confirming endocarditis when combined with the standard diagnostic criteria.

Conclusions
The VUI had good diagnostic accuracy for PVE. The diagnostic power of currently used morphometabolic parametersis significantly increased by the addition of the VUI. Integration of the VUI in the diagnostic algorithm may clarify doubtful cases, and improve the diagnostic yield of PET/CTA.

Funding Acknowledgement
Type of funding sources: None.
Mechanistic insights from a multiparametric magnetic resonance imaging study regarding the role of sodium glucose co-transporter 2 inhibitors
Authors: Thirunavukarasu S , Jex N , Chowdhary A , Hassan I , Straw S , Broadbent D , Swoboda P , Witte K K , Cubbon R , Xue H , Kellman P , Greenwood J P , Plein S , Levelt E 
Published: October 2021

Abstract

Background
Type 2 diabetes (T2D) is associated with an increased risk of heart failure (HF) and cardiovascular (CV) mortality. Sodium–glucose-co transporter-2 (SGLT2) inhibitors reduce the risk of major adverse CV events and hospitalisation for HF in T2D patients with high cardiovascular risk, despite only a modest improvement in glycemic control. Restoring cellular energy homeostasis and reversing adverse cardiac remodelling in diabetes have been speculated as a potential metabolic modulatory effect of SGLT2 inhibitors leading to their beneficial CV outcomes. Myocardial energy deficient states can be detected non-invasively by 31-phosphorus magnetic resonance spectroscopy (31P-MRS).

Objectives
Utilising cardiovascular magnetic resonance imaging (CMR) and 31P-MRS in a single centre longitudinal cohort study, we aimed to investigate the effects of the selective SGLT2 inhibitor empagliflozin on myocardial energetics, function, perfusion, and myocardial cellular volume in patients with T2D.

Methods
Eighteen consecutive T2D patients who were commenced on empagliflozin in cardiometabolic optimisation clinics underwent CMR and 31P-MRS scans before and after twelve-week empagliflozin treatment, and plasma N-terminal pro hormone B-type natriuretic peptide (NT-proBNP) levels were measured. Ten controls with no diabetes underwent an identical 31P-MRS and CMR protocol on a single visit.

Results
When compared to controls, patients with T2D showed: lower myocardial energetics (1.52±0.40 vs 2.20±0.5, p=0.0005), lower stress myocardial blood flow (1.60±0.50 vs 2.10±0.50, p=0.02) and lower left ventricular ejection fraction (52±13% vs 63±4%, p=0.01). Treatment with empagliflozin led to significant improvements in myocardial energetics (PCr/ATP: 1.52 to 1.76, p=0.009). This was accompanied by a relative 13% improvement in left ventricular ejection fraction (p=0.001), 3% improvement in global longitudinal strain (p=0.01), 61% reduction in NTproBNP (p=0.05), and 9% reduction in myocardial cell volume (p=0.04). No significant change in myocardial blood flow or diastolic strain was detected.

Conclusions
For the first time, we demonstrate that empagliflizon improves myocardial energetics and function, reduces myocardial cellular volume, and reduces NT-proBNP levels in patients with T2D.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): British Heart Foundation PCr/ATPLVEF
Derivation and validation of myocardial bridge characteristics by optical coherence tomography: a prospective multimodality imaging study
Authors: Otsuka T , Ueki Y , Losdat S , Baer S , Raeber L 
Published: October 2021

Abstract

Background
Optical coherence tomography (OCT) findings of myocardial bridge (MB) have not been established.

Purpose
We aimed to establish the OCT appearance of MB compared with the half-moon sign derived by intravascular ultrasound (IVUS) and to assess the prevalence among patients undergoing coronary angiography and OCT in clinical practice.

Methods
For derivation of the OCT appearance of MB, imaging data obtained from 122 patients undergoing OCT and IVUS for the left anterior descending artery (LAD) enrolled in two prospective imaging studies were analyzed. To assess the prevalence of OCT-derived MB, 470 patients undergoing OCT for LAD in clinical routine were analyzed.

Results
We found a homogeneous band with intermediate light intensity surrounding the vessel wall as assessed by OCT corresponding to half-moon sign derived by IVUS. Mean length, angle, and thickness of OCT-MB were 21.2±10.8mm, 205.7±56.5°, and 0.39±0.06mm, respectively. Mean length of IVUS-MB was significantly longer as compared with OCT-MB (23.7±11.9, P=0.010), while there were no significant differences in angle and thickness. MB angle was &gt;180° in approximately 50% of frames with MB. There was a strong/moderate correlation between OCT-MB and half-moon sign (MB length: r=0.81, P=0.001, MB angle: r=0.58, P=0.001). In the derivation cohort, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of OCT-MB for the milking effect by angiography were 96.3%, 62.1%, 41.9%, 98.3%, and 69.7%, respectively, and much comparable with the IVUS half-moon sign. In the validation cohort, OCT-detected MB was observed in 139 (29.6%) patients, of whom 57.6% (n=80) did not have angiographic evidence of milking effect.

Conclusion
OCT is able to identify IVUS-defined MB as homogenous band with intermediate light intensity surrounding the vessel wall. There was a high concordance in terms of MB angle and thickness between OCT and IVUS. In clinically-indicated OCT cases of the LAD, more than half of OCT-MBs were angiographically silent. OCT assessment of MB may facilitate the accurate diagnosis of MB and thus provide useful information in determining the subsequent treatment strategy for the patients with MB.

Funding Acknowledgement
Type of funding sources: None. Representative imaging of MBCase of OCT-MB without milking effect
Hypolipidemia associated with inactivation of TM6SF2 is due to decreased VLDL-lipids secretion
Authors: Luo F , Smagris E , Fletcher J A , Cohen J C , Hobbs H H 
Published: October 2021

Abstract

Background
A missense variant in Transmembrane 6 Superfamily Member 2 [TM6SF2 (E167K)] is associated with reduced plasma lipid levels and protection from coronary atherosclerosis. The substitution of lysine for glutamate at residue 167 is associated with a marked decrease in TM6SF2 protein expression, consistent with a loss-of-function mutation. However the biological role of TM6SF2 is not known, and the mechanism(s) responsible for the hypolipidemia associated with mutation gene has not been fully defined. To elucidate the pathological mechanism for the hypolipidemia associated with TM6SF2 deficiency, we inactivated Tm6sf2 in mice and rats.

Methods
Tm6sf2−/− mice were generated as described previously. Two lines of Tm6sf2−/− rats with different frameshift mutations in exon 1 were generated using CRISPR/Cas9 technology. Primary hepatocytes were isolated from WT and Tm6sf2−/− mice for microscopy. Rats were fasted 16 or 4 hours and tissues were collected on ice for cell fractionation, and in liquid nitrogen for biochemical analyses. Frozen samples were stored at −80°C for subsequent analyses.

Result
In both mice and rats, inactivation of Tm6sf2 recapitulated the phenotype of humans with the E167K substitution: steatosis, reduced plasma lipid levels, and transaminitis. The phenotype was readily apparent in animals fed chow diets. Both species had reduced secretion of VLDL-TG, as determined by TRITON WR1399 injection, with no decrease in secretion of ApoB. Experiments in isolated perfused livers from WT and Tm6sf2−/− mice confirmed that the decreased TG secretion observed in intact animals reflected reduced TG secretion from the liver. Lipidomic analysis of the liver perfusates by by LC-MS indicated that secretion of cholesteryl esters, and phospholipids was also decreased in the KO animals. Taken together, these findings are consistent with a role for TM6SF2 in lipidation of ApoB-containing lipoproteins. To further elucidate the function of TM6SF2, we used fluorescence microscopy and cell fractionation to determine the subcellular localization of the protein. Microscopic analysis showed that TM6SF2 co-localized with ER and Golgi markers, but cell fractionation studies indicated that the protein is located primarily in the smooth ER. The ratio of TG to ApoB was lower in Golgi fractions from TM6sf2−/− rats than in corresponding fractions from WT animals.

Conclusions
Since the sequela of TM6SF2 inactivation are already apparent in the Golgi, we speculate that TM6SF2 promotes lipidation of VLDL in a pre-Golgi compartment. We are currently performing additional studies to further define the specific mechanism whereby TM6SF2 promotes lipidation of ApoB-containing lipoproteins.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): National Institutes of Health
NADPH oxidase 4 has a crucial impact on the microcirculation of hypercholesteremic LDL receptor deficient mice
Authors: Diaba-Nuhoho P , Shahid A , Brunssen C , Morawietz H , Brendel H 
Published: October 2021

Abstract

Introduction
NADPH oxidase (NOX) 4-generated H2O2 has anti-atherosclerotic properties in conduit arteries like the aorta and carotids. However, the role of NOX4 on vascular function of small resistance arteries and blood pressure in a mouse model of familial hypercholesterolemia is unknown.

Purpose
We evaluated whether NOX4-generated H2O2 might play a role in perivascular adipose tissue of the thoracic aorta (tPVAT) and small resistance arteries on vascular function in a mouse model of familial hypercholesterolemia.

Methods
Aortic segments and mesenteric arteries from 26-week-old Ldlr−/− and Nox4−/− / Ldlr−/− mice were analysed by Mulvany myograph. In addition, vascular contraction and relaxation was analysed in the presence of L-NAME and catalase. Analysis of mRNA expression was performed in murine and human tissue by quantitative real-time PCR. Blood pressure was detected by tail cuff method in conscious, trained mice.

Results
Loss of NOX4 led to severe endothelial dysfunction in mesenteric arteries of Ldlr−/− mice. Blocking of NO synthases with L-NAME led to decreased endothelial relaxation in Ldlr−/− mice at the level of Nox4−/− / Ldlr−/− mice. However, incubation with L-NAME did not worsen the established endothelial dysfunction of the mesenteric arteries from Nox4−/− / Ldlr−/− mice. These results are strikingly different from the aorta, where inhibition of NO synthases led to a similarly impaired endothelial relaxation in both mouse strains. We detected a similar eNOS expression in the aorta of Ldlr−/− and Nox4−/− / Ldlr−/−, but a reduced eNOS expression in the mesenteric arteries of Nox4−/− / Ldlr−/− mice. H2O2 can induce eNOS expression. Therefore, we analysed the vascular function after catalase incubation and again found a significant reduction of endothelial function in the mesenteric arteries of Ldlr−/− mice. Finally, we analysed blood pressure of these mice and did not observe differences in systolic blood pressure, despite significant differences in endothelial function of resistant arteries.

Conclusion
NOX4 protects against severe endothelial dysfunction in the mesenteric artery in a model of hypercholesterolemia.

Funding Acknowledgement
Type of funding sources: Other. Main funding source(s): Ghanaian-German postgraduate training scholarship program (DAAD)
Resveratrol regulates cytokine secretion by cardiac microvascular endothelium under hypoxia/reoxygenation condition
Authors: Cui H , Yang Y J , Zong W J 
Published: October 2021

Abstract

Background
Microvascular endothelial injury is recently considered playing an initial role in myocardial ischemia/reperfusion injury (MIRI). Cardiac microvascular endothelial cells (CMECs) regulate cardiomyocytes and haematocytes via secreting cytokine. MIRI jeopardize not only the barrier function but also the paracrine function of microvasculature. Resveratrol, a natural polyphenolic compound, was demonstrated to protect myocardium against MIRI and to preserve the function of endothelium. However, how the paracrine function of CMECs is regulated by MIRI and resveratrol remains to be elucidated.

Purpose
The study was to illuminate the alteration of cytokine profiles secreted by CMECs under hypoxia/reoxygenation (H/R) condition and its modulation by resveratrol.

Methods
CMECs were exposed to different concentrations of resveratrol for 30 minutes and then were subjected to H/R for 12 h/2 h. Apoptotic rates were measured to determine the optimal concentration. Protein antibody arrays were performed to find the alteration of cytokine secreted into conditioned medium by CMECs. A Gene Ontology (GO) analysis was applied to interpret the functional implication of changes in cytokine profiles.

Results
Resveratrol inhibited apoptosis of CMECs in a dose-dependent manner after H/R and reached its peak effect at the concentration of 100μM, which reduced apoptosis from 27.27±2.95% to 15.01±1.36% (Figure 1A and B). The results of a cluster analysis and all significantly altered factors are shown in figure 1C (fold-change &gt;1.5; p&lt;0.05). Twenty-nine types of cytokine were significantly changed by H/R (15 factors decreased and 14 increased, Figure 2A), and resveratrol at 100μM changed 98 types of cytokine compared with the H/R group (93 factors decreased and 5 increased, Figure 2B). Among these cytokine, eight factors were increased by H/R and they were decreased by resveratrol. Eleven were attenuated by H/R and further decreased by resveratrol. Insulin-like growth factor binding protein-1 was up-regulated by H/R and it was further increased by resveratrol (Figure 2C). The factors with significant alteration were involved in cellular growth, proliferation and differentiation, as well as chemotaxis and transport.

Conclusions
Resveratrol inhibited the apoptosis of CMECs and modulated the paracrine function of cardiac microvascular endothelium under ischemia/reperfusion condition.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Natural Science Foundation Figure 1Figure 2
Progression markers of coronary calcification
Authors: Sedykh D Y U , Barbarash O L , Kashtalap V V , Hhryachkova O N , Kokov A N , Shibanova I A 
Published: October 2021

Abstract

Aim
To evaluate the relationship between clinical parameters, biomarkers of bone turnover and the progression of coronary artery calcification (CAC) in patients with stable coronary heart disease (CHD) based on long-term (5 years) follow-up.

Material and methods
The single-center, prospective, non-randomized observational study included 111 men with CHD, admitted for CABG. All patients in the preoperative period underwent the following procedures: color duplex scanning (CDS) of the brachiocephalic arteries (BCA), multi-slice computed tomography (MSCT) coronary angiography to assess the degree of CAC using the Agatson score (calculation of the coronary artery calcium score – CACS), estimation of femoral neck bone mineral density with the T-score calculation and clinical assessment of biomarkers of bone metabolism (calcium, phosphorus, calcitonin, osteopontin, osteocalcin, osteoprotegerin (OPG), alkaline phosphatase, parathyroid hormone). The vital status of patients was ascertained after 3–5 years of follow-up after CABG, CDS of the BCA and MSCT-coronary angiography were repeated. To identify the most significant clinical and anamnestic risk factors and form a model of predictors of CAC progression, patients were divided into two groups depending on the high increase in CACS (an increase in the score of more than 100 Agatston units (AU).

Results
16 (14.4%) out of 111 patients failed to establish contact for the next stage of the study. In 4 (3.6%) cases death was registered (3 – fatal myocardial infarction, 1 – fatal stroke). The CAC progression was assessed in 91 patients (81.9%). Patients who showed signs of CAC progression comprised a group of 60 (65.9%) patients; without CAC progression – 31 (34.1%) patients. The “end points” in the groups were comparable and were detected in 18 cases (19.7%): recurrent angina in 16 patients (p=0.368), non-fatal myocardial infarction in 1 (p=0.162) and 1 emergency stenting (p=0,162) of the coronary artery that was not subjected to CABG. The risk model for CAC progression included an initial decrease in femoral neck bone mineral density and nonadherence to statins for 5 years after CABG (p=0.001).

Conclusion
65.9% of men with stable CHD showed the signs of CAC progression for 5 years after CABG, according to MSCT. The main predictors of CAC were: low cathepsin K levels and low bone mineral density in the preoperative period, low OPG 5 years post-CABG.

Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): Federal State Budgetary Institution “Research Institute for Complex Issues of Cardiovascular Diseases”; 6, Sosnovy Blvd, Kemerovo, 650002, Russia
Autoantibodies directed against apolipoprotein A-1 as a potential contributor to non-alcoholic fatty liver disease
Authors: Pagano S , Alfaiate D , Juillard C , Frias M , Magenta A , Martino F , Sciaqua A , Succurro E , Burger F , Brandt K J , Andreozzi F , Mach F , Perticone M , Vuilleumier N 
Published: October 2021

Abstract

Background
Non-Alcoholic Fatty Liver Disease (NAFLD) represents an increasing cause of liver disease worldwide. Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in these patients. Although NAFLD pathophysiology is not fully understood alterations in fat metabolism seem to play a role. Autoantibodies against apolipoprotein A-1 (anti-apoA-1 IgG) are a novel cardiovascular risk factor to which have been recently attributed a metabolic role in addition to a well-established macrophage-mediated inflammatory effect and have a function as a disruptor of the cholesterol pathway.

Purpose
This study aims at evaluating a possible role of anti-apoA-1 IgG in NAFLD.

Methods
Serum from 137 NAFLD patients were tested for anti-apoA-1 IgG prevalence. In vitro, SREBP1, SREBP2 expressions were assessed in the human hepatic cell line HepaRG by western blot analysis and bodipy staining was used to evaluate the lipid droplet content. Mescoscale technology platform was used to measure TNF-α, IL-6 and IL-8 cytokines/chemokines in HepaRG supernatants. Oil Red O staining was used to detect lipid accumulation in liver sections from ApoE−/− mice.

Results
Elevated anti-apoA-1 IgG seropositivity was found in patients with NAFLD (46%). In vitro, anti-apoA-1 IgG and not control IgG induced lipid accumulation in hepatic cells (5.9 vs 2.5, P=0.0008) and this lipid overload was associated with a high SREBP1 but not SREBP2 expression. Furthermore, anti-apoA-1 IgG and not control antibodies caused a significant large increase of the proinflammatory cytokines IL-6 (680 vs. 163 pg/mL, P=0.03) and TNF-α (391 vs 266 pg/mL, P=0.04) as well as of the chemokine IL-8 (174.1 vs. 72.6 ng/mL, P=0.03) detected in the hepatic cell supernatants. In vivo, anti-apoA-1 IgG and not control IgG also induced higher lipid accumulation in the livers of ApoE−/− mice (1.23 vs 0.53, P=0.03).

Conclusion
Anti-apoA-1 IgG are frequent in NAFLD, cause a strong inflammatory response and promote lipid accumulation through SREBP1 activation in human hepatic cells. We hypothesize that anti-apoA1 IgG may be a potential contributor in the development of NAFLD.

Funding Acknowledgement
Type of funding sources: Public hospital(s). Main funding source(s): Geneva University Hospital