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2.
Eur J Cardiothorac Surg ; 65(5)2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38730543

RESUMO

OBJECTIVES: The aim of this study was to describe trends and outcomes for patients undergoing surgical aortic valve replacement (SAVR) in the Netherlands. METHODS: The Netherlands Heart Registration database was used to report the number and outcomes of isolated, primary SAVR procedures performed from 2007 to 2018 in adult patients. RESULTS: A total of 17 142 procedures were included, of which 77.9% were performed using a biological prosthesis and 21.0% with a mechanical prosthesis. Median logistic EuroSCORE I decreased from 4.6 [interquartile range (IQR) 2.4-7.7] to 4.0 (IQR 2.6-6.0). The 120-day mortality decreased from 3.3% in 2007 to 0.7% in 2018. The median duration of follow-up was 76 months (IQR 53-111). Ten-year survival, when adjusted for age, EuroSCORE I and body surface area, was 72.4%, and adjusted 10-year freedom from reinvervention was 98.1%. Additional analysis for patients under the age of 60 showed no difference between patients treated with a biological or mechanical prosthesis in adjusted 10-year survival, 89.7% vs 91.9±%, respectively (P = 0.25), but a significant difference in adjusted 10-year freedom from reintervention, 90.0±% vs 95.9%, respectively (P < 0.01). CONCLUSIONS: Between 2007 and 2018, age and risk profile of patients undergoing SAVR decreased, especially for patients treated with a biological prosthesis. The 120-day mortality decreased over time. Patients undergoing SAVR nowadays have a risk of 120-day mortality of <1% and 10-year freedom from valve-related reintervention of >95%.


Assuntos
Valva Aórtica , Implante de Prótese de Valva Cardíaca , Humanos , Masculino , Países Baixos/epidemiologia , Feminino , Idoso , Valva Aórtica/cirurgia , Implante de Prótese de Valva Cardíaca/tendências , Implante de Prótese de Valva Cardíaca/estatística & dados numéricos , Implante de Prótese de Valva Cardíaca/mortalidade , Implante de Prótese de Valva Cardíaca/métodos , Pessoa de Meia-Idade , Resultado do Tratamento , Próteses Valvulares Cardíacas/tendências , Idoso de 80 Anos ou mais , Sistema de Registros , Estenose da Valva Aórtica/cirurgia , Estenose da Valva Aórtica/mortalidade , Fatores de Risco
3.
Neth Heart J ; 32(4): 173-181, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38358408

RESUMO

INTRODUCTION: Postoperative atrial fibrillation (POAF) is a common phenomenon following cardiac surgery. In this study, we assessed current preventive strategies used by Dutch cardiothoracic centres, identified common views on this matter and related these to international guidelines. METHODS: We developed an online questionnaire and sent it to all cardiothoracic surgery centres in the Netherlands. The questionnaire concerned the management of POAF and the use of pharmaceutical therapies (beta-blockers and calcium antagonists) and non-pharmaceutical methods (posterior left pericardiotomy, pericardial flushing and epicardial botulinum toxin type A injections). Usage of electrical cardioversions, anticoagulants and left atrial appendage closure were also enquired. RESULTS: Of the 15 centres, 14 (93%) responded to the survey and 13 reported a POAF incidence, ranging from 20 to 30%. Of these 14 centres, 6 prescribed preoperative AF prophylaxis to their patients, of which non-sotalol beta-blockers were prescribed most commonly (57%). Postoperative medication was administered by all centres and included non-sotalol beta-blockers (38%), sotalol (24%), digoxin (14%), calcium antagonists (13%) and amiodarone (10%). Only 2 centres used posterior left pericardiotomy or pericardial flushing as surgical manoeuvres to prevent POAF. Moreover, respondents expressed the need for guidance on anticoagulant use. CONCLUSION: Despite the use of various preventive strategies, the reported incidence of POAF was similar in Dutch cardiothoracic centres. This study highlights limited use of prophylactic amiodarone and colchicine, despite recommendations by numerous guidelines, and restricted implementation of surgical strategies to prevent POAF.

4.
Cell Tissue Res ; 394(3): 497-514, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37833432

RESUMO

We aim to elucidate how miRNAs regulate the mRNA signature of atrial fibrillation (AF), to gain mechanistic insight and identify candidate targets for future therapies. We present combined miRNA-mRNA sequencing using atrial tissues of patient without AF (n = 22), with paroxysmal AF (n = 22) and with persistent AF (n = 20). mRNA sequencing previously uncovered upregulated epithelial to mesenchymal transition, endothelial cell proliferation and extracellular matrix remodelling involving glycoproteins and proteoglycans in AF. MiRNA co-sequencing discovered miRNAs regulating the mRNA expression changes. Key downregulated miRNAs included miR-135b-5p, miR-138-5p, miR-200a-3p, miR-200b-3p and miR-31-5p and key upregulated miRNAs were miR-144-3p, miR-15b-3p, miR-182-5p miR-18b-5p, miR-4306 and miR-206. MiRNA expression levels were negatively correlated with the expression levels of a multitude of predicted target genes. Downregulated miRNAs associated with increased gene expression are involved in upregulated epithelial and endothelial cell migration and glycosaminoglycan biosynthesis. In vitro inhibition of miR-135b-5p and miR-138-5p validated an effect of miRNAs on multiple predicted targets. Altogether, the discovered miRNAs may be explored in further functional studies as potential targets for anti-fibrotic therapies in AF.


Assuntos
Fibrilação Atrial , MicroRNAs , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Fibrilação Atrial/genética , Transição Epitelial-Mesenquimal/genética , Átrios do Coração/metabolismo , RNA Mensageiro
5.
J Transl Med ; 21(1): 366, 2023 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-37280612

RESUMO

BACKGROUND: Epicardial adipose tissue (EAT) secretome induces fibrosis. Fibrosis, primarily extracellular matrix (ECM) produced by fibroblasts, creates a substrate for atrial fibrillation (AF). Whether the EAT secretome from patients with AF activates human atrial fibroblasts and through which components, remains unexplored. RESEARCH AIMS: (a) To investigate if the EAT secretome from patients with versus without AF increases ECM production in atrial fibroblasts. (b) To identify profibrotic proteins and processes in the EAT secretome and EAT from patients with, who will develop (future onset), and without AF. METHODS: Atrial EAT was obtainded during thoracoscopic ablation (AF, n = 20), or open-heart surgery (future onset and non-AF, n = 35). ECM gene expression of human atrial fibroblasts exposed to the EAT secretome and the proteomes of EAT secretome and EAT were assessed in patients with and without AF. Myeloperoxidase and neutrophil extracellular traps (NETs) were assessed immunohistochemically in patients with paroxysmal, persistent, future onset, and those who remain free of AF (non-AF). RESULTS: The expression of COL1A1 and FN1 in fibroblasts exposed to secretome from patients with AF was 3.7 and 4.7 times higher than in patients without AF (p < 0.05). Myeloperoxidase was the most increased protein in the EAT secretome and EAT from patients with versus without AF (FC 18.07 and 21.57, p < 0.005), as was the gene-set neutrophil degranulation. Immunohistochemically, myeloperoxidase was highest in persistent (FC 13.3, p < 0.0001) and increased in future onset AF (FC 2.4, p = 0.02) versus non-AF. Myeloperoxidase aggregated subepicardially and around fibrofatty infiltrates. NETs were increased in patients with persistent versus non-AF (p = 0.03). CONCLUSION: In AF, the EAT secretome induces ECM gene expression in atrial fibroblasts and contains abundant myeloperoxidase. EAT myeloperoxidase was increased prior to AF onset, and both myeloperoxidase and NETs were highest in persistent AF, highlighting the role of EAT neutrophils in the pathophysiology of AF.


Assuntos
Fibrilação Atrial , Humanos , Tecido Adiposo/metabolismo , Fibrilação Atrial/metabolismo , Fibrose , Átrios do Coração/patologia , Pericárdio/metabolismo , Peroxidase/metabolismo
6.
J Clin Med ; 12(7)2023 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-37048733

RESUMO

INTRODUCTION: Atrial fibrillation (AF) is more prevalent in men than in women. However, women with AF are more symptomatic, have a worse quality of life, a higher stroke risk and may therefore benefit most from ablation. In this study we aim to identify the risk of recurrent AF after thoracoscopic ablation, and assess the differential impact of the risk factors for recurrence between women and men. METHOD: This is a single center cohort study, including patients undergoing thoracoscopic ablation for advanced AF between 2008 and 2019. All patients were clinically followed up for two years with quarterly 24 h Holter monitoring and ECGs for the detection of recurrent AF. Left atrial appendage (LAA) tissue was collected for collagen analysis. RESULTS: We included 571 patients, of whom 143 (25%) were women. Women were older than men (63 ± 8.3 y vs. 59 ± 8.5, p < 0.001), but had fewer cardiovascular risk factors, myocardial infarctions (1.4% vs. 6.5%, p = 0.03) and, in particular, vascular disease (7.0% vs. 16.1%, p = 0.01). Women suffered more from AF recurrence, driven by more atrial tachycardias, and sex was an independent risk factor for recurrence (HR1.41 [1.04-1.91], p = 0.028]). The presence of vascular disease was associated with an increased risk for AF recurrence in women, but not in men. In LAA histology, women had more collagen than men, as had patients with persistent compared to paroxysmal AF. CONCLUSION: Women had 15% more recurrences, driven by more atrial tachycardias, which may be explained by a more fibrotic atrial substrate. What's new? Women undergoing thoracoscopic AF ablation have a higher risk of recurrent AF, driven by more atrial tachycardias. Among patients with left atrial enlargement or persistent AF, women have worse outcomes than men. Vascular disease was a risk factor for recurrence in women, but not in men. In a histopathologic analysis of the left atrial appendage, women had more collagen than men, as had patients with persistent compared to paroxysmal AF.

7.
Rev Esp Cardiol (Engl Ed) ; 76(6): 417-426, 2023 Jun.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-36155846

RESUMO

INTRODUCTION AND OBJECTIVES: Recent observations suggest that patients with a previous failed catheter ablation have an increased risk of atrial fibrillation (AF) recurrence after subsequent thoracoscopic AF ablation. We assessed the risk of AF recurrence in patients with a previous failed catheter ablation undergoing thoracoscopic ablation. METHODS: We included patients from 3 medical centers. To correct for potential heterogeneity, we performed propensity matching to compare AF freedom (freedom from any atrial tachyarrhythmia> 30 s during 1-year follow-up). Left atrial appendage tissue was analyzed for collagen distribution. RESULTS: A total of 705 patients were included, and 183 had a previous failed catheter ablation. These patients had fewer risk factors for AF recurrence than ablation naïve controls: smaller indexed left atrial volume (40.9± 12.5 vs 43.0±12.5 mL/m2, P=.048), less congestive heart failure (1.5% vs 8.9%, P=.001), and less persistent AF (52.2% vs 60.3%, P=.067). However, AF history duration was longer in patients with a previous failed catheter ablation (6.5 [4-10.5] vs 4 [2-8] years; P<.001). In propensity matched analysis, patients with a failed catheter ablation were at a 68% higher AF recurrence risk (OR, 1.68; 95%CI, 1.20-2.15; P=.034). AF freedom was 61.1% in patients with a previous failed catheter ablation vs 72.5% in ablation naïve matched controls. On histology of the left atrial appendage (n=198), patients with a failed catheter ablation had a higher density of collagen fibers. CONCLUSIONS: Patients with a prior failed catheter ablation had fewer risk factors for AF recurrence but more frequently had AF recurrence after thoracoscopic AF ablation than ablation naïve patients. This may in part be explained by more progressed, subclinical, atrial fibrosis formation.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Humanos , Fibrilação Atrial/complicações , Fibrilação Atrial/cirurgia , Resultado do Tratamento , Átrios do Coração , Fibrose , Ablação por Cateter/efeitos adversos , Recidiva
8.
Perfusion ; 38(7): 1360-1383, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-35961654

RESUMO

The landmark 2016 Minimal Invasive Extracorporeal Technologies International Society (MiECTiS) position paper promoted the creation of a common language between cardiac surgeons, anesthesiologists and perfusionists which led to the development of a stable framework that paved the way for the advancement of minimal invasive perfusion and related technologies. The current expert consensus document offers an update in areas for which new evidence has emerged. In the light of published literature, modular minimal invasive extracorporeal circulation (MiECC) has been established as a safe and effective perfusion technique that increases biocompatibility and ultimately ensures perfusion safety in all adult cardiac surgical procedures, including re-operations, aortic arch and emergency surgery. Moreover, it was recognized that incorporation of MiECC strategies advances minimal invasive cardiac surgery (MICS) by combining reduced surgical trauma with minimal physiologic derangements. Minimal Invasive Extracorporeal Technologies International Society considers MiECC as a physiologically-based multidisciplinary strategy for performing cardiac surgery that is associated with significant evidence-based clinical benefit that has accrued over the years. Widespread adoption of this technology is thus strongly advocated to obtain additional healthcare benefit while advancing patient care.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Adulto , Humanos , Procedimentos Cirúrgicos Cardíacos/métodos , Circulação Extracorpórea/métodos , Perfusão , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Coração
9.
Int J Cardiovasc Imaging ; 38(12): 2615-2624, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36445663

RESUMO

To assess transthoracic echocardiographic (TTE) left atrial (LA) strain parameters and their association with atrial fibrillation (AF) recurrence after thoracoscopic surgical ablation (SA) in patients in sinus rhythm (SR) or in AF at baseline. Patients participating in the Atrial Fibrillation Ablation and Autonomic Modulation via Thoracoscopic Surgery trial were included. All patients underwent thoracoscopic pulmonary vein isolation with LA appendage exclusion and were randomized to ganglion plexus (GP) or no GP ablation. In TTEs performed before surgery, LA strain and mechanical dispersion (MD) of the LA reservoir and conduit phase in all patients, and of the contraction phase in patients in SR were obtained. Recurrence of AF was defined as any documented atrial tachyarrhythmia lasting > 30 s during one year of follow-up. Two hundred and four patients (58.6 ± 7.8 years, 73% male, 57% persistent AF) were included. At baseline TTE 121 (59%) were in SR and 83 (41%) had AF. Patients with AF recurrence had lower LA strain of the reservoir phase (13.0% vs. 16.6%; p = < 0.001) and a less decrease in strain of the conduit phase (-9.0% vs. -11.8%; p = 0.006), regardless of rhythm. MD of the conduit phase was larger in patients with AF recurrence (79.4 vs. 43.5 ms; p = 0.012). Multivariate cox regression analysis demonstrated solely an association between LA strain of the reservoir phase and AF recurrence in patients in SR (HR 0.95, p = 0.046) or with AF (HR 0.90, p = 0.038). A reduction in LA strain of the reservoir phase prior to SA predicts recurrence of AF in both patients with SR or AF. Left atrial strain assessment may therefore add to a better patient selection for SA.


Assuntos
Apêndice Atrial , Fibrilação Atrial , Veias Pulmonares , Humanos , Masculino , Feminino , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/cirurgia , Valor Preditivo dos Testes , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/cirurgia , Veias Pulmonares/diagnóstico por imagem , Veias Pulmonares/cirurgia
10.
J Cardiovasc Surg (Torino) ; 63(1): 91-98, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34308612

RESUMO

BACKGROUND: The effect of prosthesis-patient mismatch (PPM) on late survival after aortic valve replacement (AVR) in patient with symptomatic severe aortic stenosis (AS) remains unclear. Also, late follow-up in previous studies is confined to only one decade. We aimed to determine the effect of PPM on late survival after isolated AVR for symptomatic severe AS during 25 years of follow-up. METHODS: In this retrospective cohort study, Kaplan-Meier survival analysis was performed to determine late survival in 404 consecutive patients with moderate PPM (N.=86), severe (N.=11), or no/mild PPM (N.=307) after isolated AVR for symptomatic severe AS during a mean follow-up of 25.0±2.9 years. Moderate, severe, and no/mild PPM were defined as indexed effective orifice area of >0.65≤0.85, ≤0.65, and >0.85 cm2/m2, respectively. Multivariable analysis was performed to identify possible independent predictors of decreased late survival, including moderate or severe PPM. RESULTS: Late survival of patients with severe PPM was worse in comparison with those with no/mild PPM: 7.4±2.6 (95% confidence interval 2.2-12.5) vs. 13.6±0.5 (95% confidence interval 12.6-14.6) years, respectively; P=0.020. Late survival of patients with moderate PPM was similar to those with no/mild PPM. Severe PPM was an independent predictor of decreased late survival: hazards ratio 4.002 (95% confidence interval 1.869-8.569); P<0.001. Moderate PPM was not an independent predictor of decreased late survival. CONCLUSIONS: Severe PPM was independently associated with decreased late survival after isolated AVR for symptomatic severe AS during a mean follow-up of 25.0±2.9 years. Therefore, severe PPM should be prevented as much as possible.


Assuntos
Estenose da Valva Aórtica/cirurgia , Valva Aórtica/cirurgia , Implante de Prótese Vascular/instrumentação , Próteses Valvulares Cardíacas , Complicações Pós-Operatórias/etiologia , Desenho de Prótese , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/mortalidade , Estenose da Valva Aórtica/fisiopatologia , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/mortalidade , Hemodinâmica , Humanos , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/fisiopatologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
12.
J Clin Med ; 10(17)2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34501375

RESUMO

BACKGROUND: Studies on very long-term outcomes after aortic valve replacement are sparse. METHODS: In this retrospective cohort study, long-term outcomes during 25.1 ± 2.8 years of follow-up were determined in 673 patients who underwent aortic valve replacement with or without concomitant coronary artery bypass surgery for severe aortic stenosis and/or regurgitation. Independent predictors of decreased long-term survival were determined. Cumulative incidence rates of major adverse events in patients with a mechanical versus those with a biologic prosthesis were assessed, as well as of major bleeding events in patients with a mechanical prosthesis under the age of 60 versus those above the age of 60. RESULTS: Impaired left ventricular function, severe prosthesis-patient mismatch, and increased aortic cross-clamp time were independent predictors of decreased long-term survival. Left ventricular hypertrophy, a mechanical or biologic prosthesis, increased cardiopulmonary bypass time, new-onset postoperative atrial fibrillation, and the presence of symptoms did not independently predict decreased long-term survival. The risk of major bleeding events was higher in patients with a mechanical in comparison with those with a biologic prosthesis. Younger age (under 60 years) did not protect patients with a mechanical prosthesis against major bleeding events. CONCLUSIONS: Very long-term outcome data are invaluable for careful decision-making on aortic valve replacement.

13.
Cancers (Basel) ; 13(15)2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34359557

RESUMO

Pediatric sarcoma patients with pleuropulmonary lesions have a dismal prognosis because the impossibility to obtain local control. The aim of this study was to determine if pleuropneumonectomy (PP) could be a therapeutic option. We retrospectively reviewed nine patients who underwent salvage PP for pleuropulmonary localization of primary localized sarcoma or metastatic recurrence. Surgery and complications were analyzed, pulmonary function tests were conducted, and quality of life was determined with EORTC-QLQ-C30 questionnaire. At the time of PP age was between 9-17 years. Underlying disease included metastatic osteosarcoma (n = 5), Ewing sarcoma (two metastatic, one primary), and one primary undifferentiated sarcoma. Early complications occurred in three patients. Mean postoperative hospitalization stay was 14.5 days. Pulmonary function test showed 19-66% reduction of total lung capacity which led to mild exercise intolerance but did not affect daily life. Four patients died of multi-metastatic relapse <14 months after PP, one patient had a local recurrence, and four patients are in complete remission between 1.5 and 12 years after PP. In conclusion, in this small patient group treated with a pleuropneumonectomy for primary or metastatic lesions, outcome is variable; however, this extended surgical technique was generally quite well tolerated. Postoperative lung function seems well preserved, and it seems to lead to at least an extension of life with good quality and therefor can be considered as salvage therapy.

14.
Heart Rhythm ; 18(12): 2115-2125, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34332113

RESUMO

BACKGROUND: To which extent atrial remodeling occurs before atrial fibrillation (AF) is unknown. OBJECTIVE: The PREventive left atrial appenDage resection for the predICtion of fuTure Atrial Fibrillation (PREDICT-AF) study investigated such subclinical remodeling, which may be used for risk stratification and AF prevention. METHODS: Patients (N = 150) without a history of AF with a CHA2DS2-VASc score of ≥2 at an increased risk of developing AF were included. The left atrial appendage was excised and blood samples were collected during elective cardiothoracic surgery for biomarker discovery. Participants were followed for 2 years with Holter monitoring to determine any atrial tachyarrhythmia after a 50-day blanking period. RESULTS: Eighteen patients (12%) developed incident AF, which was associated with increased tissue gene expression of collagen I (COL1A1), collagen III (COL3A1), and collagen VIII (COL8A2), tenascin-C (TNC), thrombospondin-2 (THBS2), and biglycan (BGN). Furthermore, the fibroblast activating endothelin-1 (EDN1) and sodium voltage-gated channel ß subunit 2 (SCN2B) were associated with incident AF whereas the Kir2.1 channel (KCNJ2) tended to downregulate. The plasma levels of COL8A2 and TNC correlated with tissue expression and predicted incident AF. A gene panel including tissue KCNJ2, COL1A1, COL8A2, and EDN1 outperformed clinical prediction models in discriminating incident AF. CONCLUSION: The PREDICT-AF study demonstrates that atrial remodeling occurs long before incident AF and implies future potential for early patient identification and therapies to prevent AF (ClinicalTrials.gov identifier NCT03130985).


Assuntos
Apêndice Atrial , Fibrilação Atrial , Remodelamento Atrial/fisiologia , Matriz Extracelular , Átrios do Coração , Idoso , Apêndice Atrial/patologia , Apêndice Atrial/cirurgia , Fibrilação Atrial/sangue , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/prevenção & controle , Biglicano/metabolismo , Biomarcadores/análise , Biomarcadores/sangue , Procedimentos Cirúrgicos Cardíacos/métodos , Colágeno/metabolismo , Eletrocardiografia Ambulatorial/métodos , Eletrocardiografia Ambulatorial/estatística & dados numéricos , Matriz Extracelular/metabolismo , Matriz Extracelular/patologia , Feminino , Átrios do Coração/patologia , Átrios do Coração/fisiopatologia , Humanos , Masculino , Valor Preditivo dos Testes , Prognóstico , Procedimentos Cirúrgicos Profiláticos/métodos , Tenascina/metabolismo , Trombospondinas/metabolismo
15.
Sci Rep ; 11(1): 2972, 2021 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-33536523

RESUMO

Despite our expanding knowledge about the mechanism underlying atrial fibrillation (AF), the interplay between the biological events underlying AF remains incompletely understood. This study aimed to identify the functionally enriched gene-sets in AF and capture their interconnection via pivotal factors, that may drive or be driven by AF. Global abundance of the proteins in the left atrium of AF patients compared to control patients (n = 3/group), and the functionally enriched biological processes in AF were determined by mass-spectrometry and gene set enrichment analysis, respectively. The data were validated in an independent cohort (n = 19-20/group). In AF, the gene-sets of innate immune system, metabolic process, cellular component disassembly and ion homeostasis were up-regulated, while the gene-set of ciliogenesis was down-regulated. The innate immune system was over-represented by neutrophil degranulation, the components of which were extensively shared by other gene-sets altered in AF. In the independent cohort, an activated form of neutrophils was more present in the left atrium of AF patients with the increased gene expression of neutrophil granules. MYH10, required for ciliogenesis, was decreased in the atrial fibroblasts of AF patients. We report the increased neutrophil degranulation appears to play a pivotal role, and affects multiple biological processes altered in AF.


Assuntos
Fibrilação Atrial/imunologia , Degranulação Celular/imunologia , Ativação de Neutrófilo , Neutrófilos/imunologia , Fibrilação Atrial/patologia , Fibrilação Atrial/cirurgia , Estudos de Casos e Controles , Ablação por Cateter , Fibroblastos/metabolismo , Átrios do Coração/imunologia , Átrios do Coração/patologia , Humanos , Masculino , Cadeias Pesadas de Miosina/metabolismo , Neutrófilos/metabolismo , Miosina não Muscular Tipo IIB/metabolismo , Proteômica
16.
EClinicalMedicine ; 31: 100661, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33385125

RESUMO

BACKGROUND: Prolonged or excessive bleeding after cardiac surgery can lead to a broad spectrum of secondary complications. One of the underlying causes is incomplete wound drainage, with subsequent accumulation of blood and clots in the pericardium. We developed the continuous postoperative pericardial flushing (CPPF) therapy to improve wound drainage and reduce postoperative blood loss and bleeding-related complications after cardiac surgery. This study compared CPPF to standard care in patients after coronary artery bypass grafting (CABG). METHODS: This is a single center, open label, randomized trial that enrolled patients at the Amsterdam UMC, location AMC, Amsterdam, the Netherlands. The study was registered at the 'Netherlands Trial Register', study identifier NTR5200 [1]. Adults undergoing CABG were randomly assigned to receive CPPF therapy or standard care, participants and investigators were not masked to group assignment. The primary end point was postoperative blood loss in the first 12-hours after surgery. FINDINGS: Between the January 15, 2014 and the March 13, 2017, 169 patients were enrolled and assigned to CPPF therapy (study group; n = 83) or standard care (control group; n = 86). CPPF reduced postoperative blood loss when compared to standard care (median differences -385 ml, reduction 76% p=≤0.001), with the remark that these results are overestimated due to a measurement error in part of the study group. None of patients in the study group required reoperation for non-surgical bleeding versus 3 (4%, 95% CI -0.4% to 7.0%) in the control group. None of the patients in the study group suffered from cardiac tamponade, versus 3 (4%, 95% CI -0,4% to 7.0%) in the control group. The incremental cost-effectiveness ratio was €116.513 (95% bootstrap CI €-882.068 to €+897.278). INTERPRETATION: The use of CPPF therapy after CABG seems to reduce bleeding and bleeding related complications. With comparable costs and no improvement in Qualty of Life (QoL), cost consideration for the implementation of CPPF is not relevant. None of the patients in the study group required re-interventions for non-surgical bleeding or acute cardiac tamponade, which underlines the proof of concept of this novel therapy. FUNDING: This study was funded by ZonMw, the Netherlands organization for health research and development (project 837001405).

17.
Crit Care Med ; 49(4): 661-670, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33405410

RESUMO

OBJECTIVES: In this study, we hypothesized that coronavirus disease 2019 patients exhibit sublingual microcirculatory alterations caused by inflammation, coagulopathy, and hypoxemia. DESIGN: Multicenter case-controlled study. SETTING: Two ICUs in The Netherlands and one in Switzerland. PATIENTS: Thirty-four critically ill coronavirus disease 2019 patients were compared with 33 healthy volunteers. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The microcirculatory parameters quantified included total vessel density (mm × mm-2), functional capillary density (mm × mm-2), proportion of perfused vessels (%), capillary hematocrit (%), the ratio of capillary hematocrit to systemic hematocrit, and capillary RBC velocity (µm × s-1). The number of leukocytes in capillary-postcapillary venule units per 4-second image sequence (4 s-1) and capillary RBC microaggregates (4 s-1) was measured. In comparison with healthy volunteers, the microcirculation of coronavirus disease 2019 patients showed increases in total vessel density (22.8 ± sd 5.1 vs 19.9 ± 3.3; p < 0.0001) and functional capillary density (22.2 ± 4.8 vs 18.8 ± 3.1; p < 0.002), proportion of perfused vessel (97.6 ± 2.1 vs 94.6 ± 6.5; p < 0.01), RBC velocity (362 ± 48 vs 306 ± 53; p < 0.0001), capillary hematocrit (5.3 ± 1.3 vs 4.7 ± 0.8; p < 0.01), and capillary-hematocrit-to-systemic-hematocrit ratio (0.18 ± 0.0 vs 0.11 ± 0.0; p < 0.0001). These effects were present in coronavirus disease 2019 patients with Sequential Organ Failure Assessment scores less than 10 but not in patients with Sequential Organ Failure Assessment scores greater than or equal to 10. The numbers of leukocytes (17.6 ± 6.7 vs 5.2 ± 2.3; p < 0.0001) and RBC microaggregates (0.90 ± 1.12 vs 0.06 ± 0.24; p < 0.0001) was higher in the microcirculation of the coronavirus disease 2019 patients. Receiver-operating-characteristics analysis of the microcirculatory parameters identified the number of microcirculatory leukocytes and the capillary-hematocrit-to-systemic-hematocrit ratio as the most sensitive parameters distinguishing coronavirus disease 2019 patients from healthy volunteers. CONCLUSIONS: The response of the microcirculation to coronavirus disease 2019-induced hypoxemia seems to be to increase its oxygen-extraction capacity by increasing RBC availability. Inflammation and hypercoagulation are apparent in the microcirculation by increased numbers of leukocytes and RBC microaggregates.


Assuntos
COVID-19/mortalidade , Capilares , Hipóxia/etiologia , Leucócitos , Microcirculação/fisiologia , Eritrócitos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
18.
Interact Cardiovasc Thorac Surg ; 32(2): 222-228, 2021 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-33491739

RESUMO

OBJECTIVES: Longer aortic cross-clamp (ACC) time is associated with decreased early survival after cardiac surgery. Because maximum follow-up in previous studies on this subject is confined to 28 months, it is unknown whether this adverse effect is sustained far beyond this term. We aimed to determine whether longer ACC time was independently associated with decreased late survival after isolated aortic valve replacement in patients with severe aortic stenosis during 25 years of follow-up. METHODS: In this retrospective cohort study, multivariable analysis was performed to identify possible independent predictors of decreased late survival, including ACC and cardiopulmonary bypass (CPB) time, in a cohort of 456 consecutive patients with severe aortic stenosis, who had undergone isolated aortic valve replacement between 1990 and 1993. RESULTS: Mean follow-up was 25.3 ± 2.7 years. Median (interquartile range) and mean ACC times were normal: 63.0 (20.0) and 64.2 ± 16.1 min, respectively. Age, operative risk scores and New York Heart Association class were similar in patients with ACC time above, versus those with ACC time below the median. Longer ACC time was independently associated with decreased late survival: hazards ratio (HR) 1.01 per minute increase of ACC time (95% confidence interval [CI] 1.00-1.02; P = 0.012). Longer CPB time was not associated with decreased late survival (HR 1.00 per minute increase of CPB time [95% CI 1.00-1.00; P = 0.30]). CONCLUSIONS: Longer ACC time, although still within normal limits, was independently associated with decreased late survival after isolated aortic valve replacement in patients with severe aortic stenosis.


Assuntos
Valva Aórtica/cirurgia , Implante de Prótese de Valva Cardíaca , Idoso , Idoso de 80 Anos ou mais , Aorta/cirurgia , Estenose da Valva Aórtica/cirurgia , Estudos de Coortes , Feminino , Próteses Valvulares Cardíacas , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
20.
EBioMedicine ; 55: 102744, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32344201

RESUMO

BACKGROUND: Excessive bleeding, incomplete wound drainage, and subsequent accumulation of blood and clots in the pericardium have been associated with a broad spectrum of bleeding-related complications after cardiac surgery. We developed and studied the continuous postoperative pericardial flushing (CPPF) method to improve wound drainage and reduce blood loss and bleeding-related complications. METHODS: We conducted a single-center, open-label, ITT, randomized controlled trial at the Academic Medical Center Amstserdam. Adults undergoing cardiac surgery for non-emergent valvular or congenital heart disease (CHD) were randomly assigned (1:1) to receive CPPF method or standard care. The primary outcome was actual blood loss after 12-hour stay in the intensive care unit (ICU). Secondary outcomes included bleeding-related complications and clinical outcome after six months follow-up. FINDINGS: Between May 2013 and February 2016, 170 patients were randomly allocated to CPPF method (study group; n = 80) or to standard care (control group; n = 90). CPPF significantly reduced blood loss after 12-hour stay in the ICU (-41%) when compared to standard care (median differences -155 ml, 95% confidence interval (CI) -310 to 0; p=≤0·001). Cardiac tamponade and reoperation for bleeding did not occur in the study group versus one and three in the control group, respectively. At discharge from hospital, patients in the study group were less likely to have pleural effusion in a surgically opened pleural cavity (22% vs. 36%; p = 0·043). INTERPRETATION: Our study results indicate that CPPF is a safe and effective method to improve chest tube patency and reduce blood loss after cardiac surgery. Larger trials are needed to draw final conclusions concerning the effectiveness of CPPF on clinically relevant outcomes.


Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Tamponamento Cardíaco/diagnóstico , Drenagem/métodos , Cardiopatias Congênitas/cirurgia , Derrame Pleural/diagnóstico , Complicações Pós-Operatórias/diagnóstico , Hemorragia Pós-Operatória/diagnóstico , Adulto , Idoso , Tamponamento Cardíaco/etiologia , Tamponamento Cardíaco/patologia , Tamponamento Cardíaco/cirurgia , Feminino , Seguimentos , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/patologia , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Pericárdio/patologia , Pericárdio/cirurgia , Derrame Pleural/etiologia , Derrame Pleural/patologia , Derrame Pleural/cirurgia , Complicações Pós-Operatórias/patologia , Complicações Pós-Operatórias/cirurgia , Hemorragia Pós-Operatória/etiologia , Hemorragia Pós-Operatória/patologia , Hemorragia Pós-Operatória/cirurgia , Reoperação/estatística & dados numéricos , Resultado do Tratamento
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