Aims
Inhibitors of SGLT2 (SGLT2i) have shown a positive impact in patients with chronic heart failure and reduced ejection fraction (HFrEF). Nonetheless, the direct effects of SGLT2i on cardiac cells ...and how their association with main drugs used for HFrEF affect the behaviour and signalling pathways of myocardial fibroblasts are still unknown. We aimed to determine the effects of dapagliflozin alone and in combination with sacubitril/valsartan (LCZ696) or spironolactone on the function of myocardial fibroblasts of patients with heart failure and reduced ejection fraction (HFrEF).
Methods and results
Myocardial fibroblasts isolated from HFrEF patients (n = 5) were treated with dapagliflozin alone (1 nM–1 μM) or combined with LCZ696 (100 nM) or spironolactone (100 nM). The migratory rate was determined by wound‐healing scratch assay. Expression of heart failure (HF) markers and signalling pathways activation were analysed with multiplexed protein array. Commercially available cardiac fibroblasts from healthy donors were used as Control (n = 4). Fibroblasts from HFrEF show higher migratory rate compared with control (P = 0.0036), and increased expression of HF markers fold‐change (Log2): COL1A1–1.3; IL‐1b–1.9; IL‐6–1.7; FN1–2.9 (P < 0.05). Dapagliflozin slowed the migration rate of HFrEF fibroblasts in a dose‐dependent manner and markedly decreased the expression of IL‐1β, IL‐6, MMP3, MMP9, GAL3, and FN1. SGLT2i had no effect on control fibroblasts. These effects were associated with decreased phosphorylation of AKT/GSK3 and PYK2 kinases and the signal transducer and activator of transcription (STAT). A combination of dapagliflozin + LCZ696 further decreased fibroblast migration, although it did not have a significant effect on the regulation of signalling pathways and the expression of biomarkers induced by SGLT2 inhibition alone. In contrast, the combination of dapagliflozin + spironolactone did not change the migration rate of fibroblast but significantly altered SGLT2i responses on MMP9, GAL3, and IL‐1b expression, in association with increased phosphorylation of the kinases AKT/GSK3 and ERK1/2.
Conclusions
SGLT2i, LCZ696, and spironolactone modulate the function of isolated myocardial fibroblasts from HFrEF patients through the activation of different signalling pathways. The combination of SGLT2i + LCZ696 shows an additive effect on migration, while spironolactone modifies the signalling pathways activated by SGLT2i and its beneficial effects of biomarkers of heart failure.
Injury of the circumflex artery is an uncommon but dangerous complication during mitral valve surgery. We report the case of a patient who presented an occlusion of the circumflex artery after a ...minimally invasive mitral valve repair, which was treated with angioplasty in the immediate post-operative period. (Level of Difficulty: Intermediate.)
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Transcatheter tricuspid valve repair (TTVr) has emerged as an alternative for the treatment of severe tricuspid regurgitation (TR). We report our initial experience with an edge-to-edge TTVr system ...in a high-volume institution. Methods: We included consecutive patients who underwent edge-to-edge TTVr systems. The primary efficacy endpoint was a reduction in the TR of at least one grade. The primary safety endpoint was procedure-related clinical serious adverse events. Results: A total of 28 patients underwent TTVr with edge-to-edge systems. All patients presented with at least severe TR with a high impact on quality of life (82% of patients in NYHA class ≥ III). The Triclip system was the most used device (89%). The primary efficacy endpoint was met in all patients. Only one patient experienced a procedural complication (femoral pseudoaneurysm). At three-month follow-up, 83% of patients were in NYHA I or II (18% baseline vs. 83% 3 months follow-up; p < 0.001). Echocardiography follow-up showed residual TR ≤ 2 in 79% of patients (paired p < 0.001). At the maximum follow-up (median follow up = 372 days), no patients had died. Conclusions: Edge-to-edge TTVr systems seem to represent a very valid alternative to prevent morbidity and mortality associated with TR as depicted by the favorable efficacy and safety.
Background:It is unknown if lack of polymer can provoke a different edge response in drug-eluting stents. The aim of this study was to compare edge vascular response between polymer-free ...paclitaxel-eluting stent (PF-PES) and polymer-based paclitaxel-eluting stents (PB-PES).Methods and Results:A total of 165 eligible patients undergoing percutaneous coronary intervention were prospectively randomized 1:1 to receive either PF-PES or PB-PES. Those patients with paired intravascular ultrasound (IVUS) after procedure and at 9-month follow-up were included in this analysis.Seventy-six patients with 84 lesions, divided into PB-PES (38 patients, 41 lesions) and PF-PES groups (38 patients, 43 lesions) had paired post-procedure and 9-month follow-up IVUS and were therefore included in this substudy. There was a significant lumen decrease at the proximal edge of PF-PES (from 9.02±3.06 mm2to 8.47±3.05 mm2; P=0.040), and a significant plaque increase at the distal edges of PF-PES (from 4.39±2.73 mm2to 4.78±2.63 mm2; P=0.004). At the distal edge there was a significant plaque increase in the PF-PES compared to PB-PES (+8.0% vs. –0.6%, respectively; P=0.015) with subsequent lumen reduction (–5.2% vs. +6.0%, respectively; P=0.024).Conclusions:PF-PES had significant plaque increase and lumen reduction at the distal edge as compared to PB-PES, probably due to difference in polymer-based drug-release kinetics between the 2 platforms. (Circ J 2014; 78: 2657–2664)
Over the past two decades, invasive coronary physiology assessment has advanced significantly. Despite the proven prognostic significance provided by invasive physiological assessment of lesions by ...means of fractional flow reserve or adenosine-free non-hyperaemic pressure ratios, challenges in clinical practice hinder widespread adoption and limit additional value for optimising percutaneous coronary intervention decisions. Despite notable progress, uncertainties persist, emphasising the need for further research to establish a single numerical parameter in the diagnosis of a functionally significant disease, clarify the impact of longitudinal vessel analysis, and support the relevance of pressure indices in post-intervention optimisation.
STEMI With a Massive Coronary Aneurysm Ponte Monteiro, Joel; Flores-Umanzor, Eduardo; Brugaletta, Salvatore
JACC. Case reports,
March 2020, 2020-03-00, 2020-03-01, Letnik:
2, Številka:
3
Journal Article
Recenzirano
Odprti dostop
An 83-year-old man with significant background comorbidities was admitted with an inferior ST-segment elevation myocardial infarction. During primary percutaneous coronary intervention, a giant ...aneurysm is seen in the right coronary artery. (Level of Difficulty: Beginner.)
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An 83-year-old man with significant background comorbidities was admitted with an inferior ST-segment elevation myocardial infarction. During primary…
Post-procedural minimal lumen diameter (MLD) as assessed by QCA and minimal intra-scaffold lumen area and healing score as assessed by OCT at 6 months were compared between Absorb BVS- and ...EES-treated patients stratified according to PD status.
The study sought to assess whether treatment with ticagrelor, as compared with prasugrel and clopidogrel, improves endothelium-dependent dilation throughout the course of the treatment and other ...vascular biomarkers, including systemic adenosine plasma levels.
The in vivo off-target effects of ticagrelor in post–acute coronary syndrome (ACS) patients remain poorly characterized.
Fifty-four stable post-ACS patients were sequentially exposed to each of the 3 oral P2Y12 inhibitors following a 3-period balanced Latin square crossover design with 4 weeks per treatment in 5 European centers. The primary endpoint was the assessment of endothelial function with pulse amplitude tonometry and expressed as reactive hyperemia index at treatment steady state. Secondary endpoints included reactive hyperemia index after loading or before maintenance regimen, systemic adenosine plasma levels, a wide set of vascular biomarkers, and ticagrelor or AR-C124910XX plasma levels throughout each ticagrelor period. In 9 patients, the evaluation of endothelial function was performed simultaneously by pulse amplitude tonometry and flow-mediated dilation.
Reactive hyperemia index did not differ after ticagrelor (1.970 ± 0.535) as compared with prasugrel (2.007 ± 0.640; p = 0.557) or clopidogrel (2.072 ± 0.646; p = 0.685), nor did systemic adenosine plasma levels or vascular biomarkers at any time points. P2Y12 platelet reactivity units were lower after ticagrelor as compared with clopidogrel at all time points and after maintenance dose as compared with prasugrel. Flow-mediated dilation did not differ after the maintenance dose of ticagrelor as compared with clopidogrel and prasugrel.
Ticagrelor did not improve endothelial function or increased systemic adenosine plasma levels as compared with prasugrel and clopidogrel in stabilized patients who suffered from an ACS. (Hunting for the Off-Target Properties of Ticagrelor on Endothelial Function in Humans HI-TECH; NCT02587260).
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The metallic everolimus drug-eluting stents (DES) and polymeric everolimus bioresorbable vascular scaffolds (BVS) are coated with the same antiproliferative drug. It is uncertain if, during the ...bioresorption process, the neointimal response of everolimus BVS differs from that of everolimus DES. A total of 31 lesions treated with a single everolimus BVS, and 19 lesions treated with everolimus DES and imaged with optical coherence tomography at 1 year, were investigated. Neointimal response was assessed as a percentage of uncovered struts, neointimal thickness, in-stent/scaffold area obstruction, and pattern of neointima. Both scaffolds presented with similar neointimal response. However, the everolimus BVS presented with a trend toward higher proportion of intraluminal masses than everolimus DES did. Objectives This study sought to compare the neointimal response of metallic everolimus drug-eluting stents (DES) and polymeric everolimus bioresorbable vascular scaffolds (BVS) by optical coherence tomography at 1 year. Background DES decrease the risk of restenosis by reducing the neointimal response. However, DES may impair strut coverage, and this has been associated with late stent/scaffold thrombosis. BVS may overcome the risk of stent/scaffold thrombosis when completely resorbed. It is unknown if, during the bioresorption process, the neointimal response of the everolimus BVS (Absorb, Abbott Vascular, Santa Clara, California) differs from that of the metallic everolimus DES (Xience, Abbott Vascular). Methods A total of 19 lesions were treated with a single everolimus DES, and 31 lesions were treated with everolimus BVS and imaged with optical coherence tomography at 1 year. Neointimal response was assessed as percentage of uncovered struts, neointimal thickness, in-stent/scaffold area obstruction, and pattern of neointima. Results At 1 year, no significant differences in the angiographic lumen loss were seen for the everolimus DES and everolimus BVS (0.18 ± 0.20 mm vs. 0.29 ± 0.36 mm; p = 0.42). optical coherence tomography analysis of 951 cross sections and 8,385 struts demonstrated similar rates of uncovered struts (5.3% everolimus DES vs. 4.5% everolimus BVS; p = 0.11), mean neointimal thickness (120.6 ± 46.0 μm vs. 136.1 ± 71.4 μm; p = 0.82) and in-stent/scaffold area obstruction (12.5 ± 7.1% vs. 13.6 ± 9.7%; p = 0.91), respectively. There was a trend of higher heterogenic tissue pattern of neointima (21.1% vs. 6.5%; p = 0.12) and less intraluminal masses (0% vs. 12.9%; p = 0.10) with everolimus DES than with everolimus BVS. Conclusions The everolimus BVS (Absorb) demonstrated a similar neointimal response as the everolimus DES (Xience). However, the presence of intraluminal masses at 12 months in a small proportion of patients warranted watchful follow-up of these cases.
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