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1.
Basic Res Cardiol ; 119(1): 93-112, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38170280

RESUMO

In recent years, SGLT2 inhibitors have become an integral part of heart failure therapy, and several mechanisms contributing to cardiorenal protection have been identified. In this study, we place special emphasis on the atria and investigate acute electrophysiological effects of dapagliflozin to assess the antiarrhythmic potential of SGLT2 inhibitors. Direct electrophysiological effects of dapagliflozin were investigated in patch clamp experiments on isolated atrial cardiomyocytes. Acute treatment with elevated-dose dapagliflozin caused a significant reduction of the action potential inducibility, the amplitude and maximum upstroke velocity. The inhibitory effects were reproduced in human induced pluripotent stem cell-derived cardiomyocytes, and were more pronounced in atrial compared to ventricular cells. Hypothesizing that dapagliflozin directly affects the depolarization phase of atrial action potentials, we examined fast inward sodium currents in human atrial cardiomyocytes and found a significant decrease of peak sodium current densities by dapagliflozin, accompanied by a moderate inhibition of the transient outward potassium current. Translating these findings into a porcine large animal model, acute elevated-dose dapagliflozin treatment caused an atrial-dominant reduction of myocardial conduction velocity in vivo. This could be utilized for both, acute cardioversion of paroxysmal atrial fibrillation episodes and rhythm control of persistent atrial fibrillation. In this study, we show that dapagliflozin alters the excitability of atrial cardiomyocytes by direct inhibition of peak sodium currents. In vivo, dapagliflozin exerts antiarrhythmic effects, revealing a potential new additional role of SGLT2 inhibitors in the treatment of atrial arrhythmias.


Assuntos
Fibrilação Atrial , Compostos Benzidrílicos , Glucosídeos , Células-Tronco Pluripotentes Induzidas , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Animais , Suínos , Miócitos Cardíacos , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Antiarrítmicos/farmacologia , Antiarrítmicos/uso terapêutico , Potenciais de Ação , Sódio
2.
Perfusion ; 38(6): 1203-1212, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-35608437

RESUMO

INTRODUCTION: During cardiopulmonary bypass (CPB), supranormal concentrations of oxygen are routinely administered with the intention to prevent cellular hypoxia. However, hyperoxemia may have adverse effects on patient outcome. Oxygen settings are based on the perfusionist's individual work experience rather than profound recommendations and studies analyzing the effect of oxygen levels are in need of methodological improvement. We aimed to advance perfusion technique by developing and clinically applying a formula for tailored oxygen therapy in CPB. METHODS: A formula to precalculate the oxygenator setting before CPB was developed. The newly-derived formula was then evaluated in a prospective, single-center pilot study to test whether a predefined arterial partial oxygen pressure (PaO2) of 150-250 mmHg could be reached. 80 patients were enrolled in the study between April and September 2021. RESULTS: The mean oxygen fraction calculated for the setting of the gas blender was 52% ±0,12. The mean PaO2 after initiation of the CPB was 193 ± 99 mmHg (min-max: 61-484, median 163 mmHg). 38.75% of the values were in the desired PaO2 corridor of 150 to 250 mmHg. 8.75% of all PaO2 values were below <79.9 mmHg, 31.25% between 80 and 149.9 mmHg, 38.75% between 150 and 249.9 mmHg and 21.25%>250 mmHg. CONCLUSIONS: Conceptually, perfusion technique should be goal-directed, guided by objective parameters and formulas. Although the optimal CPB oxygenation target remains unknown, it is nevertheless important to develop strategies to tailor oxygen therapy to aid in creating evidence as to what level of oxygen is best for patients during CPB. The formula we derived needs further adjustments to increase results in the target range.


Assuntos
Ponte Cardiopulmonar , Oxigênio , Humanos , Ponte Cardiopulmonar/efeitos adversos , Ponte Cardiopulmonar/métodos , Estudos Prospectivos , Projetos Piloto , Pulmão
3.
Clin Transplant ; 33(10): e13709, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31515841

RESUMO

BACKGROUND: Survival rates following cardiac transplantation continue to improve. Due to the scarcity of available organs, extended donor criteria have become more prevalent in clinical practice. In this context, the risk of developing cardiac pathology requiring surgical correction is increasing. METHODS: Between January 1991 and October 2010, a total of 479 patients received cardiac transplantations at the University Hospital Heidelberg. Of those, 18 (3.8%) patients required subsequent cardiac surgery until 2018. Short- and long-term analyses were performed. RESULTS: Indications for cardiac surgery included valvular disease (n = 16) with the majority of cases affecting the tricuspid valve (n = 10), while 6 patients received mitral valve surgery, of whom 3 patients underwent concomitant valve surgery. Other indications included CABG (n = 1) and re-transplantation (n = 1) for allograft dysfunction. Mean follow-up time was 6.5 years, while mean interval to surgery was 6.0 years. Early mortality was 11.1% (n = 2), while overall survival at 1, 5, and 10 years were, 88.1%, 81.4%, and 52.2%, respectively. Compared to an overall survival of that transplant cohort at 1, 5, and 10 years of 76.7%, 66.7%, and 52.4% percent, respectively (P = .271). CONCLUSION: According to our data, redo cardiac surgery can be performed with acceptable mortality and morbidity. Atrioventricular valve pathology plays a chief role in these patients.


Assuntos
Procedimentos Cirúrgicos Cardíacos/mortalidade , Cardiopatias/mortalidade , Transplante de Coração/mortalidade , Reoperação/mortalidade , Transplantados/estatística & dados numéricos , Idoso , Feminino , Seguimentos , Cardiopatias/patologia , Cardiopatias/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Taxa de Sobrevida , Resultado do Tratamento
4.
Thorac Cardiovasc Surg ; 67(6): 503-512, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30352477

RESUMO

BACKGROUND: Transplant vasculopathy (TV) is the main limiting factor for long-term graft survival characterized by fibrosis, myofibroblast, and smooth muscle cell (SMC) proliferation. Decoy oligodeoxynucleotide (dODN) against the transcription factor activator protein-1 (AP-1) might interfere with the expression of AV-related genes that govern neointima formation. METHODS: Aortic allografts from DBA/2 mice were incubated with control buffer, consensus, or mutated control AP-1 dODN and were transplanted into the infrarenal aorta of C57BL/6 mice. Cyclosporine A (10 mg/kg body weight [BW]) was administered daily. Explantation and histomorphometric and immunohistochemical evaluation was performed after 30 days. Matrix metalloproteinase (MMP) activity was visualized by gelatin in situ zymography. RESULTS: Intima-to-media (I/M) ratio and neointima formation were significantly reduced in the consensus AP-1 dODN treatment group by 37% (p < 0.05) and 67% (p < 0.01), respectively. SMC α-actin-2 staining and macrophage marker expression revealed a marked reduction in the neointima. I/M ratio was found to correlate with the number of tissue macrophages (p < 0.05). MMP and fibrosis marker expression were not significantly altered. CONCLUSION: Intraoperative AP-1dODN utilization might be a strategy to preserve graft function after transplantation.


Assuntos
Aorta/transplante , Doenças da Aorta/prevenção & controle , Sobrevivência de Enxerto , Oligodesoxirribonucleotídeos/metabolismo , Fator de Transcrição AP-1/metabolismo , Animais , Aorta/metabolismo , Aorta/patologia , Doenças da Aorta/genética , Doenças da Aorta/metabolismo , Doenças da Aorta/patologia , Modelos Animais de Doenças , Feminino , Fibrose , Hiperplasia , Macrófagos/metabolismo , Macrófagos/patologia , Metaloproteinases da Matriz/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Neointima , Oligodesoxirribonucleotídeos/genética , Fatores de Tempo , Fator de Transcrição AP-1/genética , Remodelação Vascular
5.
Med Sci Monit ; 23: 1017-1025, 2017 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-28236633

RESUMO

BACKGROUND Long-term follow-up data concerning isolated tricuspid valve pathology after replacement or reconstruction is limited. Current American Heart Association guidelines equally recommend repair and replacement when surgical intervention is indicated. Our aim was to investigate and compare operative mortality and long-term survival in patients undergoing isolated tricuspid valve repair surgery versus replacement. MATERIAL AND METHODS Between 1995 and 2011, 109 consecutive patients underwent surgical correction of tricuspid valve pathology at our institution for varying structural pathologies. A total of 41 (37.6%) patients underwent tricuspid annuloplasty/repair (TAP) with or without ring implantation, while 68 (62.3%) patients received tricuspid valve replacement (TVR) of whom 36 (53%) were mechanical and 32 (47%) were biological prostheses. RESULTS Early survival at 30 days after surgery was 97.6% in the TAP group and 91.1% in the TVR group. After 6 months, 89.1% in the TAP group and 87.8% in the TVR group were alive. In terms of long-term survival, there was no further mortality observed after one year post surgery in both groups (Log Rank p=0.919, Breslow p=0.834, Tarone-Ware p=0.880) in the Kaplan-Meier Survival analysis. The 1-, 5-, and 8-year survival rates were 85.8% for TAP and 87.8% for TVR group. CONCLUSIONS Surgical repair of the tricuspid valve does not show survival benefit when compared to replacement. Hence valve replacement should be considered generously in patients with reasonable suspicion that regurgitation after repair will reoccur.


Assuntos
Implante de Prótese de Valva Cardíaca/mortalidade , Implante de Prótese de Valva Cardíaca/métodos , Valva Tricúspide/patologia , Adulto , Idoso , Feminino , Seguimentos , Alemanha/epidemiologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Valva Mitral/cirurgia , Complicações Pós-Operatórias , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Valva Tricúspide/cirurgia
6.
Med Sci Monit ; 23: 3617-3626, 2017 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-28740070

RESUMO

BACKGROUND A retrospective analysis was conducted of the early and long-term outcomes after surgery for infective endocarditis (IE). MATERIAL AND METHODS We included 360 patients with IE operated upon between 1993 and 2012. The primary endpoint was overall cumulative postoperative survival at 30 days. Secondary endpoints were early postoperative outcomes and complication rates. Factors associated with 30-day mortality were analyzed. RESULTS Mean age was 58.7±14.7 years and 26.9% (n=97) were female. The mean follow-up was 4.41±4.53 years. Postoperative survival was 81.7% at 30 days, 69.4% at 1 year, 63.3% at 5 years, and 63.3% at 10 years. Non-survivors were significantly older (p=0.014), with higher NYHA Class (p=0.002), had higher rates of preoperative diabetes mellitus (p=0.005), renal failure (p=0.001), and hepatic disease (p=0.002). Furthermore, non-survivors had higher baseline alanine aminotransferase (ALT, p=0.048), aspartate transaminase (AST, p=0.027), bilirubin (p=0.013), white cell count (WCC, p=0.034), and CRP (p=0.049). Factors associated with 30-day mortality were longer duration of surgery, CPB, and aortic cross-clamping times (p<0.001, p<0.001, and p=0.003, respectively), as well as higher RBC, FFP, and platelet transfusion requirements (p<0.001, p=0.005, and p<0.001, respectively). Multivariate logistic regression analysis revealed liver cirrhosis (OR 4.583, 95-CI: 1.096-19.170, p=0.037) and longer CPB time (OR 1.025, 95-CI 1.008-1.042, p=0.004) as independent predictors of 30-day mortality. CONCLUSIONS Surgical treatment of IE shows satisfactory early, midterm, and long-term results. Multivariate logistic regression analysis revealed cirrhosis and longer CPB time as independent predictors of 30-day mortality.


Assuntos
Endocardite/mortalidade , Endocardite/cirurgia , Idoso , Idoso de 80 Anos ou mais , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
7.
Artif Organs ; 41(2): 139-145, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27653813

RESUMO

Cardiopulmonary bypass (CPB) is a known mediator of systemic inflammatory response. Extracorporeal circulations are undergoing continuous modifications and optimizations to achieve better results. Hence we aim to compare the inflammatory response associated with two recent miniature extracorporeal circulation systems during normothermic CPB. We measured plasma levels of cytokines including interleukin (IL)-1ß, IL-6, IL-10, tumor necrosis factor-α, migration inhibitory factor (MIF), receptor for advanced glycation endproduct, and cluster of differentiation 40 ligand in 60 consecutive patients during the first 24 h after CPB. The patients were prospectively randomized to one of three trial groups: patients in group A were operated with the minimal extracorporeal circulation circuit (MECC, Maquet, Rastatt, Germany), group B operated with the extracorporeal circulation circuit optimized (ECC.O, Sorin, Italy), and group C operated with a conventional extracorporeal circuit (CECC, Maquet). Arterial blood samples were collected at intervals before, 30 min after initiation, and after termination of CPB. Further samples were collected 6 and 24 h after CPB. IL-10 levels were significantly raised in the CECC group as compared with either of the mini ECC-circuits with a peak concentration at 6 h postoperatively. Human MIF concentrations were significantly higher in the CECC group starting 30 min after CPB and peaking at the end of CPB. The overall reduction in cytokine concentrations in the mini-ECC groups correlated with a lower need for blood transfusion in MECC and a shorter mechanical ventilation time for ECC.O. Normothermic CPB using minimally invasive extracorporeal circulation circuits can reduce the inflammatory response as measured by cytokine levels, which may be beneficial for perioperative preservation of pulmonary function and hemostasis in low risk patients.


Assuntos
Ponte Cardiopulmonar/efeitos adversos , Ponte Cardiopulmonar/instrumentação , Citocinas/sangue , Inflamação/sangue , Inflamação/etiologia , Miniaturização/instrumentação , Idoso , Citocinas/imunologia , Feminino , Humanos , Inflamação/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Temperatura , Resultado do Tratamento
8.
Artif Organs ; 41(6): 519-528, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27862040

RESUMO

The aim of this study was to compare patients with severe biventricular heart failure who underwent Berlin Heart Excor implantation with (cardiogenic shock [CS] status) or without the need for preoperative extracorporeal life support (ECLS) as a bridge to long-term device. A total of 40 consecutive patients with severe biventricular heart failure underwent Berlin Heart Excor implantation with (CS status, n = 20, 50%) or without (control, n = 20, 50%) the need for preoperative ECLS as a bridge to long-term device from March 2007 to May 2015 at our institution. Demographics and preoperative baseline characteristics as well as early and long-term outcomes including mortality and complication rates were retrospectively compared between the two groups. There were no statistically significant differences in terms of demographics and most preoperative clinical characteristics. The mean age in the ECLS (CS group) and control group was 43.5 ± 19.4 and 41.3 ± 16.4 (P = 0.705), whereas 20 and 25% of patients were females (P = 1.000). However, patients from the ECLS group had preoperatively higher lactate (P = 0.037), aspartate aminotransferase (P < 0.001), and alanine aminotransferase (P < 0.001) levels, all of them significantly decreased after surgery (P  = 0.004, P = 0.017, and P = 0.001, respectively) and did not show any statistical differences to the corresponding values from the control group (P = 0.597, P = 0.491, and P = 0.339, respectively). Postoperatively, patients from the control and ECLS groups had statistically similar incidences of liver failure (30 vs. 35%, P = 0.736), renal failure (45 vs. 70%, P = 0.110), need for reopening (35 vs. 60%, P = 0.113), major cerebrovascular events (35 vs. 30%, P = 0.736), sepsis (10 vs. 25%, P = 0.407), wound infection (20 vs. 30%, P = 0.716), abdominal ischemia requiring surgery (28.6 vs. 36.8%, P = 0.719), and acute respiratory distress syndrome (25 vs. 35.3%, P = 1.000). The proportion of patients who were bridged to transplantation was statistically similar between the ECLS and the control groups (40 vs. 52.6%, P = 0.429). Furthermore, there were no statistically significant differences in terms of early (Breslow [generalized Wilcoxon] P = 0.907) and long-term (log-rank [Mantel-Cox] P = 0.787) overall cumulative survival accounting for 30-day survival of 75 versus 75%, 6-month survival of 60 versus 55%, 1-year survival of 54 versus 40%, and 7-year survial of 47 versus 40% in the control and ECLS groups, respectively. ECLS in critical CS as a bridge to implantation of the Berlin Heart Excor ventricular assist device is safe and is associated with improvement in end-organ function leading to similar excellent early and long-term survival and incidences of major complications as in patients without the need for preoperative ECLS support.


Assuntos
Oxigenação por Membrana Extracorpórea , Insuficiência Cardíaca/terapia , Ventrículos do Coração/fisiopatologia , Coração Auxiliar , Adulto , Berlim , Oxigenação por Membrana Extracorpórea/efeitos adversos , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/cirurgia , Ventrículos do Coração/cirurgia , Coração Auxiliar/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Resultado do Tratamento , Função Ventricular
9.
J Heart Valve Dis ; 24(2): 228-35, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26204691

RESUMO

BACKGROUND AND AIM OF THE STUDY: Systemic lupus erythematosus (SLE) and primary/secondary antiphospholipid syndrome (APLS) may cause early degenerative changes in cardiac valves, such as Libman-Sacks endocarditis, though few reports exist of this condition. Herein are presented the early and late clinical outcomes after cardiac valve surgery in patients diagnosed with SLE and APLS in a single-center experience. METHODS: A prospective analysis was conducted of the perioperative and follow up data acquired from patients with diagnosed SLE, and primary and secondary APLS, who underwent either single or combined valve surgery at the authors' department between 2002 and 2014. RESULTS: Fifteen patients (14 females, one male; mean age 53 ± 16 years; range: 16-77 years) were identified. The mean follow up time was 49 ± 32 months (range: 12.5-119 months). Thirteen patients (11 females, two males) were diagnosed with SLE; one of these patients had tricuspid Libman-Sacks endocarditis, while two female patients had primary APLS and four had secondary APLS. Besides bioprosthetic and mechanical valve replacements, mitral and tricuspid valve reconstruction were performed. The mean cross-clamp time was 112 ± 73 min (range: 55-294 min). Early major cardiovascular events occurred in two patients, and late non-fatal events in four patients, including one thromboembolic event. The 30-day and in-hospital mortalities were both 0%. Currently, 12 patients (80%) are alive at the end of follow up. Actuarial survival was 92 ± 7.4% at one year, 74 ± 18% at four years, and 49 ± 23% at ten years. CONCLUSION: Despite general concerns, the present results confirmed that patients with SLE and APLS can be operated on for cardiac valve disease, with favorable early results and acceptable long-term outcome.


Assuntos
Síndrome Antifosfolipídica/complicações , Procedimentos Cirúrgicos Cardíacos , Doenças das Valvas Cardíacas/etiologia , Doenças das Valvas Cardíacas/cirurgia , Lúpus Eritematoso Sistêmico/complicações , Adolescente , Adulto , Idoso , Feminino , Doenças das Valvas Cardíacas/mortalidade , Próteses Valvulares Cardíacas , Implante de Prótese de Valva Cardíaca , Humanos , Pessoa de Meia-Idade , Oligopeptídeos , Complicações Pós-Operatórias/epidemiologia , Resultado do Tratamento , Adulto Jovem
10.
ESC Heart Fail ; 2024 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-38797557

RESUMO

AIMS: Combined coronary artery bypass grafting (CABG) and aortic valve replacement (AVR), and female sex are associated with increased perioperative mortality in clinical risk scores. This study investigated male-female differences in short-term outcome stratified by age groups. METHODS AND RESULTS: All patients undergoing AVR and CABG between January 2001 and June 2021 at our institution were included. 1963 patients were grouped by decades into: 59 years and younger (n = 127), 60-69 (n = 471), 70-79 (n = 1070), and 80 years and older (n = 295). The primary end points of this study were 30 and 180 days mortality. Secondary end points were influence of preoperative risk factors and impact of sex on survival and postoperative major adverse events. Female patients showed higher 30 and 180 days mortality after combined CABG and AVR surgery (8.3% vs. 4.2%, P < 0.01; 15.8% vs. 9.4%, P < 0.01). Stratified by age groups, 30 and 180 days mortality remained significantly higher in septuagenarians (9.6% vs. 2.5%, P < 0.01; 16.3% vs. 7.7%, P < 0.01). Females were significantly older, had better preserved left ventricular function, and higher incidence of diabetes mellitus compared with male patients in this subgroup (P < 0.01; P = 0.01; P < 0.01). Additionally, females received significantly less internal mammary artery (IMA) conduits (P < 0.01). Female sex (OR: 3.33, 95% CI: [1.76-6.31]; 1.93, [1.22-3.06]), higher age (1.28, [1.13-1.45]; 1.16, [1.06-1.26]), diabetes mellitus (1.93, [1.03-3.60]; 1.70, [1.08-2.67]) and LVEF <30% (3.26, [1.48-7.17]; 2.23, [1.24-4.02]) were correlated with 30 and 180 days mortality, respectively. Upon multivariable testing, sex (1.77, [1.21-2.58]) and LVEF <30% (3.71, [2.39-5.76]) remained independent predictors for major adverse postoperative events. Infrequent use of IMA grafts was associated with increased 30 and 180 days mortality as well as adverse events (0.47, [0.25-0.87]; 0.46, [0.29-0.72]; 0.61, [0.42-0.88]). CONCLUSIONS: Sex disparities in baseline characteristics may delay operative intervention in female patients. The inherent risk profiles might be responsible for outcome differences in septuagenarians.

11.
Eur J Cardiothorac Surg ; 65(4)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38530802

RESUMO

OBJECTIVES: Several short-term analyses from German Registry for Acute Aortic Dissection Type A (GERAADA) have been published. This study investigated whether short-term risk factors are transferable to the long-term prognosis of patients. METHODS: Thirty-three centres with 2686 patients participated in the long-term follow-up. A total of 1164 patients died, 1063 survived and 459 were lost to follow-up during the follow-up timeframe (mean duration: 10.2 years). Long-term mortality of the cohort was compared with an age-stratified, German population. RESULTS: One, 5 and 10 years after initial surgery, the survival of the GERAADA patient cohort was 71.4%, 63.4% and 51%, respectively. Without the early deaths (90-day mortality 25.4%), survival was calculated after 1, 5 and 10 years: 95.6%, 83.5% and 68.3%. Higher age, longer extracorporeal circulation time, shorter perioperative ventilation time and postoperative neurologic deficits were predictive of long-term prognosis. In an age-divided landmark analysis, the mortality of aortic dissection surgery survivors was found to be similar to that of the general German population. If patients are sorted in risk groups according to the GERAADA score, long-term survival differs between the risk groups. CONCLUSIONS: If patients have survived an acute postoperative period of 90 days, life expectancy comparable to that of the general German population can be assumed in lower- and medium-risk patients. Whether the GERAADA score can provide valuable insights into the long-term prognosis of patients undergoing surgery for acute aortic dissection type A is still unclear.


Assuntos
Dissecção Aórtica , Humanos , Seguimentos , Dissecção Aórtica/cirurgia , Fatores de Risco , Prognóstico , Sistema de Registros , Resultado do Tratamento , Doença Aguda , Estudos Retrospectivos
12.
Mol Ther Methods Clin Dev ; 32(1): 101163, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38178915

RESUMO

Rupture or dissection of thoracic aortic aneurysms is still the leading cause of death for patients diagnosed with Marfan syndrome. Inflammation and matrix digestion regulated by matrix metalloproteases (MMPs) play a major role in the pathological remodeling of the aortic media. Regnase-1 is an endoribonuclease shown to cleave the mRNA of proinflammatory cytokines, such as interleukin-6. Considering the major anti-inflammatory effects of regnase-1, here, we aimed to determine whether adeno-associated virus (AAV)-mediated vascular overexpression of the protein could provide protection from the development and progression of aortic aneurysms in Marfan syndrome. The overexpression of regnase-1 resulted in a marked decrease in inflammatory parameters and elastin degradation in aortic smooth muscle cells in vitro. Intravenous injection of a vascular-targeted AAV vector resulted in the efficient transduction of the aortic wall and overexpression of regnase-1 in a murine model of Marfan syndrome, associated with lower circulating levels of proinflammatory cytokines and decreased MMP expression and activity. Regnase-1 overexpression strongly improved elastin architecture in the media and reduced aortic diameter at distinct locations. Therefore, AAV-mediated regnase-1 overexpression may represent a novel gene therapy approach for inhibiting aortic aneurysms in Marfan syndrome.

13.
PLoS One ; 18(10): e0284802, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37862289

RESUMO

BACKGROUND: Transvenous laser lead extraction (TLE) for cardiac implantable electric devices (CIED) is a challenging procedure especially if performed in octogenarians. In this study we evaluated the safety and efficacy of transvenous laser lead extraction in elderly patients. METHODS: This is a retrospective study of octogenarian patients who underwent laser-assisted lead extraction (LLE) (GlideLight laser sheath, Philips, San Diego, USA). 270 Consecutive patients were included. Patients were divided into two groups. Octogenarian group and non-octogenarian group. The Data was gathered from patients treated between September 2013 and January 2020 and is retrospectively analyzed. RESULTS: Of 270 consecutive patients, 38 (14.0%) were 80 years old or more. The total number of the extracted leads was 556 among which 84(15.0%) from the Octogenarian group. From these leads were 155 single coil leads, 82 dual coil leads, 129 right ventricular pacing leads, 155 right atrial leads, and 35 left ventricular leads. In the Octogenarian group the number of removed leads was as follows: 13 single coil leads, 10 dual coil leads, 28 right ventricular pacing leads, 28 right atrial leads and 5 left ventricular leads. No mortality was recorded in the Octogenarian group. One patient in the YG suffered from a superior vena cava tear and one patient suffered from pulmonary embolism. CONCLUSION: In octogenarian laser assisted lead extraction patients is a safe and effective procedure. No increase in morbidity, mortality or perioperative complication could be recorded in this group. Age should not be a limiting factor to perform this procedure.


Assuntos
Fibrilação Atrial , Desfibriladores Implantáveis , Marca-Passo Artificial , Idoso de 80 Anos ou mais , Humanos , Idoso , Estudos Retrospectivos , Octogenários , Desfibriladores Implantáveis/efeitos adversos , Veia Cava Superior , Fibrilação Atrial/etiologia , Lasers , Remoção de Dispositivo/métodos , Marca-Passo Artificial/efeitos adversos , Resultado do Tratamento
14.
Transplant Direct ; 9(3): e1452, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36845859

RESUMO

Tricuspid valve regurgitation (TVR) is often observed after orthotopic heart transplantation. However, there is a scarcity of data regarding long-term outcomes of patients with TVR. Methods: Between January 2008 and December 2015, 169 patients underwent orthotopic heart transplantation at our center and were included in this study. TVR trends and associated clinical parameters were retrospectively analyzed. TVR was assessed after 30 d, 1 y, 3 y, and 5 y, and groups were defined according to changes in TVR grade: constant (group 1; n = 100), improvement (group 2; n = 26), and deterioration (group 3; n = 43). Survival, outcome with regard to operative technique, and long-term kidney and liver function during follow-up were assessed. Results: Mean follow-up time was 7.67 ± 4.17 y (median 8.62, Q1 5.06, Q3 11.16). Overall mortality was 42.0%, with differences between the groups (P < 0.01). Cox regression analysis revealed improvement of TVR as a significant predictor for survival (hazard ratio 0.23; 95% confidence interval, 0.08-0.63, P < 0.01). After 1 y 2.7%, after 3 y 3.7%, and after 5 y 3.9% of the patients showed persistent severe TVR. Creatinine levels after 30 d and 1, 3, and 5 y showed significant differences between the groups (P = 0.02, P < 0.01, P < 0.01, and P = 0.01), deterioration of TVR being associated with higher creatinine levels during follow-up. Conclusions: Deterioration of TVR is associated with higher mortality and renal dysfunction. Improvement of TVR may function as a positive predictor for long-term survival after heart transplantation. Improvement of TVR should be a therapeutic goal offering a prognostic value for long-term survival.

15.
JTCVS Open ; 15: 252-260, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37808068

RESUMO

Objectives: Patients with ischemic cardiomyopathy undergoing coronary artery bypass grafting (CABG) surgery may develop postcardiotomy cardiogenic shock. In these cases, implantation of an Impella 5.0 or 5.5 microaxial pump offers full hemodynamic support while simultaneously unloading of the left ventricle. Methods: Preoperative, perioperative, and postoperative data of all patients receiving postoperative support with an Impella 5.0 or 5.5 after CABG surgery between September 2017 and October 2022 were retrospectively collected. Cohort built-up was performed according to the timing of Impella implantation, either simultaneous during CABG surgery or delayed. Results: A total of n = 42 patients received postoperative Impella support, of whom 27 patients underwent simultaneous Impella implantation during CABG surgery and 15 patients underwent delayed Impella therapy. Preoperative left ventricular ejection fraction was similarly low in both groups (26.7 ± 0.7% vs 24.8 ± 11.3%; P = .32). In the delayed cohort, Impella implantation was performed after a median of 1 (1; 2) days after CABG surgery. Survival after 30 days (75.6% vs 47.6%, P = .04) and 1 year (69.4% vs 29.8%, P = .03) was better in the cohort receiving simultaneous Impella implantation. Conclusions: The combined advantages of hemodynamic support and LV unloading with microaxial pumps may lead to a favorable survival in patients with left ventricular failure following CABG surgery. Early implantation during the initial surgery shows a trend toward a more favorable survival as compared with patients receiving delayed support.

16.
J Thorac Cardiovasc Surg ; 166(1): 25-34.e8, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-34446289

RESUMO

BACKGROUND: Acute aortic Stanford type A dissection remains a frequent and life-limiting event for patients with Marfan syndrome. Outcome results in this high-risk group are limited. METHODS: The German Registry for Acute Aortic Dissection Type A collected the data of 56 centers between July 2006 and June 2015. Of 3385 patients undergoing operations for acute aortic Stanford type A dissection, 117 (3.5%) were diagnosed with Marfan syndrome. We performed a propensity score match comparing patients with Marfan syndrome with patients without Marfan syndrome in a 1:2 fashion. RESULTS: Patients with Marfan syndrome were significantly younger (42.9 vs 62.2 years; P < .001), predominantly male (76.9% vs 62.9%; P = .002), and less catecholamine dependent (9.4% vs 20.3%; P = .002) compared with the unmatched cohort. They presented with aortic regurgitation (41.6% vs 23.0%; P < .001) and involvement of the supra-aortic vessels (50.4% vs 39.5%; P = .017) more often. Propensity matching revealed 82 patients with Marfan syndrome (21 female) with no significant differences in baseline characteristics compared with patients without Marfan syndrome (n = 159, 36 female; P = .607). Although root preservation was more frequent in patients with Marfan syndrome, procedure types did not differ significantly (18.3% vs 10.7%; P = .256). Aortic arch surgery was performed more frequently in matched patients (87.5% vs 97.8%; P = .014). Thirty-day mortality did not differ between patients with and without Marfan syndrome (19.5% vs 20.1%; P = .910). Multivariate regression showed no influence of Marfan syndrome on 30-day mortality (odds ratio, 0.928; 95% confidence interval, 0.346-2.332; P = .876). CONCLUSIONS: Marfan syndrome does not adversely affect 30-day outcomes after surgical repair for acute aortic Stanford type A dissection compared with a matched cohort. Long-term outcome analysis is needed to account for the influence of further downstream interventions.


Assuntos
Dissecção Aórtica , Síndrome de Marfan , Humanos , Masculino , Feminino , Síndrome de Marfan/complicações , Síndrome de Marfan/diagnóstico , Resultado do Tratamento , Estudos Retrospectivos , Aorta/cirurgia , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/etiologia , Dissecção Aórtica/cirurgia
17.
Front Cardiovasc Med ; 10: 1108256, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36865886

RESUMO

Introduction: Kidney dysfunction is common in patients with aortic stenosis (AS) and correction of the aortic valve by transcatheter aortic valve implantation (TAVI) often affects kidney function. This may be due to microcirculatory changes. Methods: We evaluated skin microcirculation with a hyperspectral imaging (HSI) system, and compared tissue oxygenation (StO2), near-infrared perfusion index (NIR), tissue hemoglobin index (THI) and tissue water index (TWI) in 40 patients undergoing TAVI versus 20 control patients. HSI parameters were measured before TAVI (t1), directly after TAVI (t2), and on postinterventional day 3 (t3). The primary outcome was the correlation of tissue oxygenation (StO2) to the creatinine level after TAVI. Results: We performed 116 HSI image recordings in patients undergoing TAVI for the treatment of severe aortic stenosis and 20 HSI image recordings in control patients. Patients with AS had a lower THI at the palm (p = 0.034) and a higher TWI at the fingertips (p = 0.003) in comparison to control patients. TAVI led to an increase of TWI, but had no uniform enduring effect on StO2 and THI. Tissue oxygenation StO2 at both measurement sites correlated negatively with creatinine levels after TAVI at t2 (palm: ρ = -0.415; p = 0.009; fingertip: ρ = -0.519; p < 0.001) and t3 (palm: ρ = -0.427; p = 0.008; fingertip: ρ = -0.398; p = 0.013). Patients with higher THI at t3 reported higher physical capacity and general health scores 120 days after TAVI. Conclusion: HSI is a promising technique for periinterventional monitoring of tissue oxygenation and microcirculatory perfusion quality, which are related to kidney function, physical capacity, and clinical outcomes after TAVI. Clinical trial registration: https://drks.de/search/de/trial, identifier DRKS00024765.

18.
Eur J Cardiothorac Surg ; 63(6)2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37104742

RESUMO

OBJECTIVES: Age-related atherosclerosis has been shown to cause aortic stiffness and wall rigidification. This analysis aimed to correlate age and dissection extension length in a large contemporary multicentre study. We hypothesize that younger patients suffer more extensive DeBakey type I dissection due to aortic wall integrity, allowing unhindered extension within the layers. METHODS: The perioperative data of 3385 patients from the German Registry for Acute Aortic Dissection Type A were retrospectively analyzed with regard to postoperative outcomes and dissection extension. Patients with DeBakey type I aortic dissection (n = 2510) were retrospectively identified and divided into 2 age groups for comparison: ≤69 years (n = 1741) and ≥70 years (n = 769). Patients with DeBakey type II dissection or connective tissue disease were excluded from the analysis. RESULTS: In younger patients (≤69 years), aortic dissection involved the supra-aortic vessels significantly more often (52.0% vs 40.1%; P < 0.001) and extended significantly further downstream the aorta: descending aorta (68.4% vs 57.1%; P < 0.001), abdominal aorta (54.6% vs 42.1%; P < 0.001) and iliac bifurcation (36.6% vs 26.0%; P < 0.001). Consequently, younger patients also presented with significantly higher incidences of preoperative cerebral (P < 0.001), spinal (P < 0.001), visceral (P < 0.001), renal (P = 0.013) and peripheral (P < 0.001) malperfusion. In older patients (≥70 years), dissection extent was significantly more often limited to the level of the aortic arch (40.9% vs 29.2%; P < 0.001). No significant difference was found with regard to 30-day mortality (20.7% vs 23.6%; P = 0.114). CONCLUSIONS: Extensive DeBakey type I aortic dissection is less frequent in older patients ≥70 years than in younger patients. In contrast, younger patients suffer more often from preoperative organ malperfusion and associated complications. Postoperative mortality remains high irrespective of age groups.


Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Implante de Prótese Vascular , Humanos , Idoso , Estudos Retrospectivos , Implante de Prótese Vascular/efeitos adversos , Stents , Resultado do Tratamento , Aorta Abdominal , Aneurisma da Aorta Torácica/cirurgia , Doença Aguda , Complicações Pós-Operatórias
19.
Thorac Cardiovasc Surg ; 60(4): 247-54, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22252326

RESUMO

BACKGROUND: Recent studies have shown the potential of PDE-5 inhibition on acute and chronic heart failure. Nevertheless it remained unclear, how far load-reducing properties and direct effects on myocardial contractility are responsible for these observations. In the present study, we investigated the effects of vardenafil on myocardial contractility and vascular function in a dose-response study. METHODS: We performed left ventricular pressure-volume analysis in young adult rats by using a Millar microtip conductance catheter. Pressure-volume loops were recorded before and after intravenous injection of vardenafil (3, 10, 30, 100, 300 µg/kg, n = 6/group). RESULTS: Treatment with vardenafil resulted in a significant (p < 0.05) increase in the load-independent cardiac contractility parameters reaching its maximum at the dose of 100µg/kg (ESPVR: 2.15 ± 0.15 vs. 3.29 ± 0.26 mm Hg/µL; PRSW: 93.28 ± 4.04 vs. 134.90 ± 6.27 mm Hg; peak positive dP/dt/EDV: 38.73 ± 7.97 vs. 53.02 ± 3.74 mm Hg·s-1·µL-1; before versus after 100 µg/kg vardenafil). Results of the in vitro organ-bath experiments showed an augmented vasorelaxation of precontracted aortic rings after vardenafil treatment. CONCLUSION: Our data supports the hypothesis that the usage of vardenafil as "inodilators" could have beneficial effects in heart failure patients.


Assuntos
Aorta/efeitos dos fármacos , Cardiotônicos/farmacologia , Imidazóis/farmacologia , Contração Miocárdica/efeitos dos fármacos , Inibidores da Fosfodiesterase 5/farmacologia , Piperazinas/farmacologia , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia , Função Ventricular Esquerda/efeitos dos fármacos , Animais , Cateterismo Cardíaco , Cardiotônicos/administração & dosagem , Relação Dose-Resposta a Droga , Frequência Cardíaca/efeitos dos fármacos , Imidazóis/administração & dosagem , Técnicas In Vitro , Injeções Intravenosas , Masculino , Miografia , Inibidores da Fosfodiesterase 5/administração & dosagem , Piperazinas/administração & dosagem , Ratos , Ratos Sprague-Dawley , Volume Sistólico/efeitos dos fármacos , Sulfonas/administração & dosagem , Sulfonas/farmacologia , Fatores de Tempo , Triazinas/administração & dosagem , Triazinas/farmacologia , Dicloridrato de Vardenafila , Vasodilatadores/administração & dosagem , Pressão Ventricular/efeitos dos fármacos
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