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Cateterismo Cardíaco , Implantación de Prótesis de Válvulas Cardíacas , Insuficiencia de la Válvula Tricúspide , Válvula Tricúspide , Anciano , Femenino , Humanos , Masculino , Cateterismo Cardíaco/métodos , Anuloplastia de la Válvula Cardíaca/métodos , Implantación de Prótesis de Válvulas Cardíacas/métodos , Valor Predictivo de las Pruebas , Tomografía Computarizada por Rayos X/métodos , Resultado del Tratamiento , Válvula Tricúspide/diagnóstico por imagen , Válvula Tricúspide/cirugía , Insuficiencia de la Válvula Tricúspide/diagnóstico por imagen , Insuficiencia de la Válvula Tricúspide/cirugíaRESUMEN
Background: In recent years, new interventional therapies for tricuspid regurgitation (TR) demonstrated their effectiveness in reducing TR severity and improving symptoms. Currently, tricuspid transcatheter edge-to-edge repair (T-TEER) and percutaneous annuloplasty are the most widely used techniques in Europe. In this retrospective study, we compared procedural characteristics and learning curves of both TR devices in a real-world cohort. Material and methods: Eligible patients with severe to torrential TR underwent either percutaneous annuloplasty or T-TEER as recommended by the local heart team. Patients with combined mitral and tricuspid interventions were excluded from the analysis. The study focused on procedural characteristics, TR reduction and learning curves. Results: A total of 122 patients underwent either percutaneous annuloplasty (n = 64) or T-TEER (n = 58) with a technical and device success rate of 98% and 97%, respectively. Reasons for technical failure included right coronary artery (RCA) dissection prior to percutaneous annuloplasty, and two single leaflet device attachments (SLDA) during T-TEER implantation. The mean improvement of TR severity was 2.4 ± 0.8 degrees after T-TEER and 2.5 ± 0.8 after percutaneous annuloplasty. T-TEER procedures were shorter in terms of both procedure time and radiation exposure, while percutaneous annuloplasty, although taking longer, showed a significant reduction in procedure time over the course of the analysed period. Conclusion: In summary, both interventional therapies reduce TR severity by approximately two degrees when used in the appropriate anatomy. The learning curve for annuloplasty group showed a significant decrease of procedure times.
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Background: Transcatheter annuloplasty is meant to target annular dilatation and is therefore mainly applied in functional tricuspid regurgitation (TR). Due to recent recognition of varying disease pathophysiology and differentiation of ventricular and atrial functional TR (VFTR and AFTR), comparative data regarding procedural success for both disease entities are required. Methods: In this consecutively enrolled observational cohort study, 65 patients undergoing transcatheter annuloplasty with a Cardioband® device were divided into VFTR (n = 35, 53.8%) and AFTR (n = 30, 46.2%). Procedural success was assessed by comparing changes in annulus dilatation, vena contracta (VC) width, effective regurgitation orifice area (EROA), as well as reduction in TR severity. Results: Overall, improvement of TR by at least two grades was achieved in 59 patients (90.8%), and improvement of TR by at least three grades was realised in 32 patients (49.2%). Residual TR of ≤2 was observed in 52 patients (80.0%). No significant differences in annulus diameter reduction [VFTR: 11â mm (9-13) vs. AFTR: 12â mm (9-16), p = 0.210], VC reduction [12â mm (8-14) vs. 12â mm (7-14), p = 0.868], and EROA reduction [0.62â cm2 (0.45-1.10) vs. 0.54â cm2 (0.40-0.70), p = 0.204] were reported. Improvement by at least two grades [27 (90.0%) vs. 32 (91.4%), p = 1.0] and three grades [14 (46.7%) vs. 18 (51.4%), p = 0.805] was similar in VFTR and AFTR, respectively. No significant difference in the accomplishment of TR grade of ≤2 [21 (70.0%) vs. 31 (88.6%), p = 0.118] was noted. Conclusion: According to our results from a real-world scenario, transcatheter annuloplasty with the Cardioband® device may be applied in both VFTR and AFTR with evidence of significant procedural TR reduction.
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BACKGROUND: Stroke aetiology remains cryptogenic in a relevant proportion of patients with acute ischaemic stroke (AIS). We assessed whether enhanced diagnostic workup after AIS yields a higher rate of prespecified pathological findings compared with routine diagnostic care in-hospital. METHODS: Hospitalised patients with AIS were prospectively enrolled in the investigator-initiated observational HEart and BRain Interfaces in Acute Ischaemic Stroke (HEBRAS) study at the Charité, Berlin, Germany. Patients with AIS without known atrial fibrillation (AF) underwent cardiovascular MR imaging (CMR), MR-angiography of the aortic arch and prolonged Holter-ECG monitoring on top of routine diagnostic care. RESULTS: Among 356 patients with AIS (mean age 66 years, 37.6% female), enhanced workup yielded a higher rate of prespecified pathological findings compared with routine care (17.7% vs 5.3%; p<0.001). Consequently, fewer patients were classified as cryptogenic after enhanced diagnostic workup (38.5% vs 45.5%, p<0.001). Routine care included echocardiography in 228 (64.0%) patients. CMR was successfully performed in 292 (82.0%) patients and revealed more often a prespecified pathological finding compared with routine echocardiography (16.1% vs 5.3%). Furthermore, study-related ECG monitoring (median duration 162 hours (IQR 98-210)) detected AF in 16 (4.5%) patients, while routine monitoring (median duration 51 hours (IQR 34-74)) detected AF in seven (2.0%) patients. CONCLUSIONS: Enhanced diagnostic workup revealed a higher rate of prespecified pathological findings in patients with AIS compared with routine diagnostic care and significantly reduced the proportion of patients with cryptogenic stroke. TRIAL REGISTRATION NUMBER: NCT02142413.
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Background: Transcatheter edge-to-edge repair (TEER) has developed from innovative technology to an established treatment strategy of mitral regurgitation (MR). The risk of iatrogenic mitral stenosis after TEER is, however, a critical factor in the conflict of interest between maximal reduction of MR and minimal impairment of left ventricular filling. We aim to investigate systematically the impact of device position on the post treatment hemodynamic outcome by involving the patient-specific segmentation of the diseased mitral valve. Materials and methods: Transesophageal echocardiographic image data of ten patients with severe MR (age: 57 ± 8 years, 20% female) were segmented and virtually treated with TEER at three positions by using a position based dynamics approach. Pre- and post-interventional patient geometries were preprocessed for computational fluid dynamics (CFD) and simulated at peak-diastole with patient-specific blood flow boundary conditions. Simulations were performed with boundary conditions mimicking rest and stress. The simulation results were compared with clinical data acquired for a cohort of 21 symptomatic MR patients (age: 79 ± 6 years, 43% female) treated with TEER. Results: Virtual TEER reduces the mitral valve area (MVA) from 7.5 ± 1.6 to 2.6 ± 0.6 cm2. Central device positioning resulted in a 14% smaller MVA than eccentric device positions. Furthermore, residual MVA is better predictable for central than for eccentric device positions (R 2 = 0.81 vs. R 2 = 0.49). The MVA reduction led to significantly higher maximal diastolic velocities (pre: 0.9 ± 0.2 m/s, post: 2.0 ± 0.5 m/s) and pressure gradients (pre: 1.5 ± 0.6 mmHg, post: 16.3 ± 9 mmHg) in spite of a mean flow rate reduction by 23% due to reduced MR after the treatment. On average, velocities were 12% and pressure gradients were 25% higher with devices in central compared to lateral or medial positions. Conclusion: Virtual TEER treatment combined with CFD is a promising tool for predicting individual morphometric and hemodynamic outcomes. Such a tool can potentially be used to support clinical decision making, procedure planning, and risk estimation to prevent post-procedural iatrogenic mitral stenosis.
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An 86-year-old patient experienced progressive heart failure symptoms. Echocardiographic evaluation revealed severe tricuspid regurgitation, which was treated by transcatheter edge-to-edge repair. During the procedure, single leaflet device attachment occurred. On the basis of a prohibitive surgical risk, caval valve implantation was performed, with no notable complications. (Level of Difficulty: Advanced.).
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BACKGROUND: Tricuspid regurgitation is gaining importance due to its high morbidity and mortality. Especially in the elderly, novel technologies in percutaneous therapies have become valuable options due to the commonly present high surgical risk. CASE PRESENTATION: We report a case of a 78-year-old female suffering from massive tricuspid regurgitation with repetitive right-sided heart failure hospitalizations. As the patient was very frail and deemed as high surgical risk, we used the TriClip® system to improve her symptomatic status. During diagnostic work-up, an additional membrane separating the right atrium, consistent with the definition of a cor triatriatum dexter, was found. Although increasing the complexity of the procedure, implantation of 3 clips with reduction of tricuspid regurgitation to a mild-to-moderate degree was achieved without any notable complications. The patient was discharged with ameliorated symptoms on the fourth postoperative day. CONCLUSIONS: Our case highlights the feasibility of percutaneous edge-to-edge tricuspid valve repair in an elderly woman with cor triatriatum dexter. Accurate echocardiographic visualization is an absolute requirement to gain access to the tricuspid valve without interacting with prevailing additional membranes.
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BACKGROUND: Atherosclerotic cardiovascular disease is the leading cause of death and disability in the Western world. OBJECTIVE: To characterise adults with confirmed coronary heart disease (CHD) and primary heterozygous familial or non-familial hypercholesterolaemia or mixed dyslipidaemia who received alirocumab in a real-world setting. METHODS: This open, prospective, multicentre, non-interventional study, conducted in Germany, enroled patients with confirmed CHD who were treated with alirocumab according to its summary of product characteristics. Prescription was at the physician's discretion and independent of study participation. Patients were followed for 12 weeks after alirocumab initiation. RESULTS: In total, 245 patients (mean age 62.2 years; 34.0% female) were documented at 90 sites. Overall, 47.7% had familial hypercholesterolaemia, 48.9% non-familial hypercholesterolaemia and 43.8% mixed dyslipidaemia; 74.6% had hypertension and 29.2% diabetes mellitus. The most common lipid-lowering therapy in the 12 months preceding alirocumab was a statin, often in combination with ezetimibe (73.5%). Statin contraindications were documented for 46.2% patients and statin intolerance for 63.8%. The mean low-density lipoprotein cholesterol (LDL-C)-level prior to alirocumab was 150.5±51.6 mg/dL. Alirocumab prescription was in compliance with German national recommendations and/or European guidelines. The most common starting dose was 75 mg every other week. Overall, 57% patients reached target LDL-C levels (<70 mg/dL) after 12 weeks of treatment. Alirocumab was generally well tolerated. CONCLUSION: In a real-world setting in Germany, alirocumab was prescribed for patients with atherosclerotic cardiovascular disease who had high baseline LDL-C levels with or without statin intolerance. Efficacy and safety were consistent with findings observed in the ODYSSEY Phase III programme.
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Anticuerpos Monoclonales Humanizados/administración & dosificación , Enfermedad Coronaria/tratamiento farmacológico , Lípidos/sangre , Biomarcadores/sangre , Enfermedad Coronaria/sangre , Enfermedad Coronaria/epidemiología , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Alemania/epidemiología , Humanos , Hipercolesterolemia/sangre , Hipercolesterolemia/complicaciones , Hipercolesterolemia/tratamiento farmacológico , Incidencia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Severe tricuspid regurgitation (TR) has limited treatment options and is associated with high morbidity and mortality. AIMS: We evaluated the safety and effectiveness of the Cardioband tricuspid valve reconstruction system from the ongoing European single-arm, multicentre, prospective TriBAND post-market clinical follow-up study. METHODS: Eligible patients had chronic symptomatic functional TR despite diuretic therapy and were deemed candidates for transcatheter tricuspid repair by the local Heart Team. RESULTS: Sixty-one patients had ≥severe functional TR. At baseline, 85% of patients were in NYHA Class III-IV, 94% had ≥severe TR (core laboratory-assessed) with 6.8% EuroSCORE II and 53% LVEF. Device success was 96.7%. At discharge, 59% (p<0.001) of patients achieved ≤moderate TR and 78% had at least one grade TR reduction. At 30 days, all-cause mortality and composite MAE rates were 1.6% and 19.7%, respectively; septolateral annular diameter was reduced by 20%, where 69% of patients achieved ≤moderate TR and 85% of patients had at least one grade TR reduction (all p<0.001). Mid-RVEDD, RA volume, and IVC diameter decreased by 10% (p=0.005), 21% (p<0.001), and 11% (p=0.022), respectively; 74% were in NYHA Class I-II (p<0.001) with improvements in overall KCCQ score by 17 points (p<0.001). CONCLUSIONS: In the TriBAND study, the Cardioband tricuspid system demonstrated favourable outcomes at discharge and 30 days in a challenging patient population with symptomatic ≥severe functional TR. Results showed significant reductions in annular diameter and TR severity, accompanied by early evidence of right heart remodelling and improvements in functional status and quality of life.
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Implantación de Prótesis de Válvulas Cardíacas , Insuficiencia de la Válvula Tricúspide , Cateterismo Cardíaco , Estudios de Seguimiento , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Humanos , Estudios Prospectivos , Calidad de Vida , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del Tratamiento , Insuficiencia de la Válvula Tricúspide/diagnóstico por imagen , Insuficiencia de la Válvula Tricúspide/cirugíaRESUMEN
BACKGROUND: Chronic mitral regurgitation (MR) is one of the most common valvular heart diseases and is associated with poor outcomes. Although other structural diseases are regularly seen in such patients, concomitant atrial septal defects (ASDs) remain a rarity in the elderly. CASE SUMMARY: We report a case of an 82-year-old woman with progressive right-sided heart failure (HF) due to MR and an ASD of secundum type, despite optimal medical therapy. Combined transcatheter mitral valve repair (MVR) by utilizing a separate transseptal puncture and ASD closure was performed resulting in amelioration of symptoms. DISCUSSION: Procedural planning for simultaneous transcatheter therapies of coupled structural heart disease entities remains complex. Our case illustrates feasibility of percutaneous edge-to-edge MVR and consecutive closure of a large secundum ASD. Different options of accessing the left atrium should be discussed on an individual basis, while additional ASD closure may be beneficial in terms of right ventricular function and symptoms of right HF.
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BACKGROUND: Transesophageal echocardiography (TEE) as a guiding tool for edge-to-edge transcatheter tricuspid valve repair (EETVr) using MitraClip (Abbott Vascular, Santa Clara, USA) may not offer sufficient image quality in a significant proportion of patients. OBJECTIVES: Intracardiac echocardiography (ICE) as additional guiding tool in EETVr with the MitraClip device. METHODS: Appropriate angulations of the ICE catheter to visualize each commissure of the tricuspid valve were established in 3D printed heart models. In a single tertiary-care center ICE was used to support EETVr as additional guidance when TEE image quality was insufficient. Procedural safety and outcomes up to 30-days were compared between ICE/TEE and TEE only guided patients. RESULTS: In 6 of 11 patients (54.5%) undergoing EETVr with MitraClip TEE alone was unsatisfactory, necessitating additional ICE guidance. In 4 of these 6 patients ICE enabled a successful completion of the procedure. The steering maneuvers identified in the 3D models were well applicable in all patients, providing examples for potential future ICE implementation in EETVr. Under both TEE alone (nâ=â5) and ICE (nâ=â6) guidance the rate of procedural complications was 0%. According to vena contracta values at discharge significant TR reduction was achievable in the treated cohort (pâ=â0.011). At 30-days follow-up one patient (ICE guided) died following global heart failure, not associated with the procedure itself. CONCLUSIONS: ICE guidance may offer an additional tool to guide EETVr with the MitraClip device in patients with poor TEE quality, as it enables successful results without impairing procedural safety.
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Catéteres Cardíacos/normas , Procedimientos Quirúrgicos Cardíacos/métodos , Ecocardiografía Transesofágica/métodos , Válvula Tricúspide/diagnóstico por imagen , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Resultado del Tratamiento , Válvula Tricúspide/cirugíaRESUMEN
BACKGROUND: High surgical risk patients presenting with severe mitral valve regurgitation (MR) and concomitant aortic valve disease are frequently a challenge for the interdisciplinary heart team meeting. If open-heart surgery for severe MR is performed, aortic stenosis (AS) or regurgitation (AR) is corrected during the same procedure if at least moderate severity of AS or AR has been confirmed. In patients with prohibitive surgical risk, optimal management strategies in the light of available transcatheter interventions still needs to be established. METHODS AND RESULTS: In this retrospective single center study, we aimed to investigate the impact of coincident moderate aortic valve disease on the outcome of patients undergoing MitraClip for severe MR. In 286 MitraClip procedures performed in our institution, 21 patients (7,3%) were identified to suffer from concomitant moderate AS and 28 patients had moderate AR (9,8%). Patients with AS were found to have a higher incidence of >moderate MR following the procedure when compared to patients without aortic valve disease (14,3% vs. 8,9%, pâ=â0.001). No differences between the groups were found regarding a combined endpoint of all cause deaths and heart failure hospitalizations after 1 year follow up (no aortic-valve disease vs. moderate AS: 19% vs 18%; pâ=â0,881 and no aortic valve disease vs moderate AR: 19% vs. 25%; pâ=â0.477). However, mortality was significantly higher in patients with coincidental moderate AR (3.8% patients without aortic valve disease, 5% in patients with AS, 17,9% in patients with AR; pâ=â0.006). CONCLUSION: According to our analysis coincidental Aortic valve stenosis may be associated with worse technical results regarding residual MR after MitraClip. Although our results regarding a combined endpoint of all-cause mortality and heart failure hospitalizations within one year of follow up were comparable between the groups, patients with moderate AR had significantly higher mortality rates. Due to the limited number of patients, our study is only hypothesis generating. Larger trials are necessary to confirm our result.
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Estenosis de la Válvula Aórtica/etiología , Procedimientos Quirúrgicos Cardíacos/métodos , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Insuficiencia de la Válvula Mitral/cirugía , Anciano , Anciano de 80 o más Años , Estenosis de la Válvula Aórtica/cirugía , Femenino , Humanos , Masculino , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Optimal timing for percutaneous mitral regurgitation (MR) treatment using MitraClip (Abbott Vascular) remains unclear. We evaluated the outcome after MitraClip in patients with moderate resting MR, progressing to severe exercise- induced MR (MR2+) compared to patients with severe resting MR (MR3). METHODS: We retrospectively investigated 221 patients undergoing MitraClip. All-cause deaths and heart failure (HF) hospitalizations were assessed as the combined primary endpoint. RESULTS: We identified 55 MR2+ and 166 MR3 patients. At baseline, MR3 patients showed higher STS scores (6.7 ± 7.3 vs 4.4 ± 5.5; P<.01), more HF hospitalizations in the 2 years prior to the procedure (51% vs 29%; P<.01), worse left ventricular ejection fraction (44.9 ± 16.5% vs 52.5 ± 14.3%; P<.01), larger left ventricular end-diastolic diameter (LVEDd; 57.0 ± 9.3 mm vs 51.7 ± 8.2 mm; P<.001), and larger left atrial volumes (118.3 ± 55.8 mL vs 98.6 ± 35.2 mL; P=.02). Long-term outcome according to the combined endpoint was significantly worse in MR3 patients (P=.01). HF hospitalizations significantly declined in both groups 2 years after MitraClip (P<.001 in MR3 patients, P=.03 in MR2+ patients). Multivariate Cox regression analysis revealed LVEDd (hazard ratio, 1.035; 95% confidence interval, 1.005-1.066; P=.02) and previous HF hospitalizations (hazard ratio, 1.813; 95% confidence interval, 1.016-3.234; P=.04) as strong outcome predictors. CONCLUSIONS: Symptomatic patients with moderate resting and severe exercise-induced MR during handgrip echocardiography may represent an MR cohort at an earlier disease stage with improved treatment response following MitraClip implantation compared to individuals with severe resting MR. Larger left ventricular diameters and preprocedural HF hospitalizations were identified as independent adverse outcome predictors.
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Implantación de Prótesis de Válvulas Cardíacas , Efectos Adversos a Largo Plazo , Anuloplastia de la Válvula Mitral , Insuficiencia de la Válvula Mitral , Válvula Mitral , Cateterismo Cardíaco/métodos , Ecocardiografía/métodos , Femenino , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Implantación de Prótesis de Válvulas Cardíacas/métodos , Humanos , Estimación de Kaplan-Meier , Efectos Adversos a Largo Plazo/diagnóstico , Efectos Adversos a Largo Plazo/mortalidad , Masculino , Persona de Mediana Edad , Válvula Mitral/diagnóstico por imagen , Válvula Mitral/cirugía , Anuloplastia de la Válvula Mitral/efectos adversos , Anuloplastia de la Válvula Mitral/métodos , Insuficiencia de la Válvula Mitral/diagnóstico , Insuficiencia de la Válvula Mitral/fisiopatología , Insuficiencia de la Válvula Mitral/cirugía , Evaluación de Procesos y Resultados en Atención de Salud , Resistencia Física , Índice de Severidad de la Enfermedad , Volumen Sistólico , Instrumentos Quirúrgicos , Evaluación de Síntomas/métodos , Evaluación de Síntomas/estadística & datos numéricosRESUMEN
Introduction: Dyslipidemia, particularly elevated low-density lipoprotein cholesterol (LDL-C), is a key risk factor for atherosclerotic cardiovascular disease (ASCVD), and lipid-lowering drugs are beneficial for the primary and secondary prevention of cardiovascular (CV) disease. While statins are clear first-line drugs, new drug developments such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to improve cardiovascular outcomes when added to statins. Evolocumab reduced the risk of cardiovascular events in patients with ASCVD when added to maximally tolerated statin therapy (± ezetimibe), and recent data from the ODYSSEY OUTCOMES trial indicate that alirocumab added to maximally tolerated statin therapy (± other lipid-lowering drugs) reduces the risk of cardiovascular events in patients with a recent acute coronary syndrome. In this article the authors review the available data on the effect of PCSK9 inhibitors on cardiovascular outcomes.Areas covered: This article reviews the available data on the effect of PCSK9 inhibitors on CV outcomes. Relevant papers were identified from a search of PubMed/Medline and the Cochrane Central Register of Controlled Trials (CENTRAL).Expert opinion: The authors conclude that PCSK9 inhibitors provide substantial and durable reductions in LDL-C levels and improve cardiovascular outcomes.
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Anticolesterolemiantes/uso terapéutico , Aterosclerosis/prevención & control , Inhibidores de PCSK9 , Humanos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
AIMS: Heart failure with preserved ejection fraction (HFpEF) and pathological cardiac aging share a complex pathophysiology, including extracellular matrix remodelling (EMR). Protease-activated receptor 2 (PAR2) deficiency is associated with EMR. The roles of PAR1 and PAR2 have not been studied in HFpEF, age-dependent cardiac fibrosis, or diastolic dysfunction (DD). METHODS AND RESULTS: Evaluation of endomyocardial biopsies from patients with HFpEF (n = 14) revealed that a reduced cardiac PAR2 expression was associated with aggravated DD and increased myocardial fibrosis (r = -0.7336, P = 0.0028). In line, 1-year-old PAR2-knockout (PAR2ko) mice suffered from DD with preserved systolic function, associated with an increased age-dependent α-smooth muscle actin expression, collagen deposition (1.7-fold increase, P = 0.0003), lysyl oxidase activity, collagen cross-linking (2.2-fold increase, P = 0.0008), endothelial activation, and inflammation. In the absence of PAR2, the receptor-regulating protein caveolin-1 was down-regulated, contributing to an augmented profibrotic PAR1 and transforming growth factor beta (TGF-ß)-dependent signalling. This enhanced TGF-ß/PAR1 signalling caused N-proteinase (ADAMTS3) and C-proteinase (BMP1)-related increased collagen I production from cardiac fibroblasts (CFs). PAR2 overexpression in PAR2ko CFs reversed these effects. The treatment with the PAR1 antagonist, vorapaxar, reduced cardiac fibrosis by 44% (P = 0.03) and reduced inflammation in a metabolic disease model (apolipoprotein E-ko mice). Patients with HFpEF with upstream PAR inhibition via FXa inhibitors (n = 40) also exhibited reduced circulating markers of fibrosis and DD compared with patients treated with vitamin K antagonists (n = 20). CONCLUSIONS: Protease-activated receptor 2 is an important regulator of profibrotic PAR1 and TGF-ß signalling in the heart. Modulation of the FXa/FIIa-PAR1/PAR2/TGF-ß-axis might be a promising therapeutic approach to reduce HFpEF.
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Cardiomiopatías/metabolismo , Fibrosis/metabolismo , Miocardio/metabolismo , Receptor PAR-2 , Anciano , Animales , Cardiomiopatías/patología , Femenino , Fibrosis/patología , Insuficiencia Cardíaca Diastólica/metabolismo , Humanos , Masculino , Ratones , Ratones Noqueados , Persona de Mediana Edad , Miocardio/patología , Receptor PAR-2/deficiencia , Receptor PAR-2/genética , Receptor PAR-2/metabolismo , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
Whereas statistical association of hepatitis C virus (HCV) infection with cardiomyopathy is long known, establishment of a causal relationship has not been achieved so far. Patients with advanced heart failure (HF) are mostly unable to tolerate interferon (IFN)-based treatment, resulting in limited experience regarding the possible pathogenic role of HCV in this patient group. HCV infection often triggers disease in a broad spectrum of extrahepatic organs, with innate immune and autoimmune pathogenic processes involved. The fact that worldwide more than 70 million patients are chronically infected with HCV illustrates the possible clinical impact arising if cardiomyopathies were induced or aggravated by HCV, resulting in progressive HF or severe arrhythmias. A novel path has been opened to finally resolve the long-standing question of cause-effect relationship between HCV infection and cardiac dysfunction, by the recent development of IFN-free, highly efficient, and well tolerable anti-HCV regimens. The new direct-acting antiviral (DAA) agents are highly virus-specific and lack unspecific side-effects upon cardiac function which have always confounded the interpretation of IFN treatment data. The actual frequency of unexplained HF in chronic HCV infection will be determined from a planned large-scale study. Whereas such patients probably constitute a rather small fraction of all those harboring HCV, they have major clinical relevance. It is not yet known which fraction of these patients will significantly benefit from HCV eradication, but this issue will be addressed now in a prospective study.
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BACKGROUND: Percutaneous catheter-based left atrial appendage closure (LAAC) is a procedure being increasingly performed in patients with atrial fibrillation and high bleeding risk. OBJECTIVE: The purpose of this study was to evaluate the incidence of magnetic resonance imaging (MRI)-detected acute brain lesions (ABLs) as well as potential changes in neurocognitive function after percutaneous LAAC in patients with atrial fibrillation. METHODS: Brain MRI at 3 T was performed within 24 hours before and after LAAC along with neurologic (National Institutes of Health Stroke Scale [NIHSS] score) and cognitive (Montreal Cognitive Assessment [MoCA] test) assessment. Acquired MRI sequences included high-resolution diffusion-weighted imaging as well as fluid-attenuated inversion recovery. RESULTS: Successful device implantation was achieved in all 23 patients (age 74.1 ± 10.5 years; 16 male) using the Amulet (n = 18), Occlutech (n = 3), or LAmbre (n = 2) device. Thirty-seven ABLs were detected by MRI in 12 of 23 patients (52%) after LAAC. The number of periprocedural LAA angiographies was significantly higher in patients with ABL than in those without ABL (1.67 ± 0.65 vs 1.18 ± 0.41; P = .048) and was associated with a higher number of ABL (ρ = 0.615; P = .033). Compared to pre-LAAC assessment, post-LAAC MoCA and NIHSS scores revealed similar results. After LAAC, MoCA test (mean 24.1 ± 4.6 vs 23.2 ± 4.6; P = .09) and NIHSS score (mean 1.0 ± 1.7 vs 1.2 ± 1.8; P = .1) were similar between patients with and those without ABL, respectively. CONCLUSION: MRI-detected ABLs are commonly observed after percutaneous LAAC. The number of LAA angiographies is significantly associated with the number of ABLs; however, the clinical implications of ABL have yet to be determined.