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1.
Artigo em Inglês | MEDLINE | ID: mdl-38719137

RESUMO

OBJECTIVE: Residual aortic dissection (AD) following DeBakey type I AD repair is associated with a high rate of adverse events that need additional intervention or surgery. This study aimed to identify clinical and early post-operative computed tomography (CT) imaging factors associated with adverse events in patients with type I AD after ascending aorta replacement. METHODS: This single centre, retrospective cohort study included consecutive patients with type I AD who underwent ascending aorta replacement from January 2011 to December 2017 and post-operative CT within 3 months. The primary outcome was AD related adverse events, defined as AD related death and re-operation due to aortic aneurysm or impending rupture. The location and size of the primary intimal tears, aortic diameter, and false lumen status were evaluated. Regression analyses were performed to identify factors associated with AD related adverse events. A decision tree model was used to classify patients as high or low risk. RESULTS: Of 103 participants (55.43 ± 13.94 years; 49.5% males), 24 (23.3%) experienced AD related adverse events. In multivariable Cox regression analysis, connective tissue disease (hazard ratio [HR] 15.33; p < .001), maximum aortic diameter ≥ 40 mm (HR 4.90; p < .001), and multiple (three or more) intimal tears (HR 7.12; p < .001) were associated with AD related adverse events. The 3 year cumulative survival free from AD related events was lower in the high risk group with aortic diameter ≥ 40 mm and multiple intimal tears (41.7% vs. 90.9%; p < .001). CONCLUSION: Early post-operative CT findings indicating a maximum aortic diameter ≥ 40 mm and multiple intimal tears may predict a higher risk of adverse events. These findings suggest the need for careful monitoring and more vigilant management approaches in these cases.

2.
Clin Transplant ; 38(4): e15304, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38591111

RESUMO

INTRODUCTION: This study aimed to compare postoperative outcomes after cardiac surgery in solid-organ transplant recipients and nontransplant patients. METHODS: We performed a retrospective analysis of 78 consecutive transplant recipients who underwent cardiac surgery at Asan Medical Center between 2000 and 2022 and were matched with 312 nontransplant patients who underwent cardiac surgery at a 1:4 ratio. The outcomes included 30-day mortality, all-cause death, cardiac death, readmission, and cardiac readmission. RESULTS: There was no significant difference in baseline characteristics between the two groups. The most common type of cardiac surgery performed in solid organ transplant recipients was isolated valve surgery, followed by isolated CABG. The 30-day mortality was not significantly different between transplant recipients and nontransplant patients (3.9% vs. 3.5%; P > .99). Solid organ transplant recipients showed a higher all-cause mortality compared to nontransplant patients (29.1% vs. 14.3% at 5 years; P = .001); however, there was no significant difference in cardiac death between the two groups (2.6% vs. 3.2% at 5 years; P = .80). In addition, the readmission and cardiac readmission rates showed comparable findings to that of mortality. CONCLUSION: Cardiac surgery can be performed safely in solid organ transplant recipients, with postoperative cardiovascular outcomes comparable to those observed in nontransplant patients.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Transplante de Órgãos , Humanos , Estudos Retrospectivos , Transplantados , Análise por Pareamento , Complicações Pós-Operatórias/etiologia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Transplante de Órgãos/efeitos adversos
3.
J Chest Surg ; 57(3): 242-251, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38472122

RESUMO

Background: This study compared the outcomes of surgical aortic valve replacement (AVR) in patients aged 50 to 70 years based on the type of prosthetic valve used. Methods: We compared patients who underwent mechanical AVR to those who underwent bioprosthetic AVR at our institution between January 2000 and March 2019. Competing risk analysis and the inverse probability of treatment weighting (IPTW) method based on propensity score were employed for comparisons. Results: A total of 1,580 patients (984 patients with mechanical AVR; 596 patients with bioprosthetic AVR) were enrolled. There was no significant difference in early mortality between the mechanical AVR and bioprosthetic AVR groups (0.9% vs. 1.7%, p=0.177). After IPTW adjustment, the risk of all-cause mortality was significantly higher in the bioprosthetic AVR group than in the mechanical AVR group (hazard ratio [HR], 1.39; 95% confidence interval [CI], 1.07-1.80; p=0.014). Competing risk analysis revealed lower risks of stroke (sub-distributional hazard ratio [sHR], 0.44; 95% CI, 0.28-0.67; p<0.001) and anticoagulation- related bleeding (sHR, 0.35; 95% CI, 0.23-0.53; p<0.001) in the bioprosthetic AVR group. Conversely, the risk of aortic valve (AV) reintervention was higher in the bioprosthetic AVR group (sHR, 6.14; 95% CI, 3.17-11.93; p<0.001). Conclusion: Among patients aged 50 to 70 years who underwent surgical AVR, those receiving mechanical valves showed better survival than those with bioprosthetic valves. The mechanical AVR group exhibited a higher risk of stroke and anticoagulation-related bleeding, while the bioprosthetic AVR group showed a higher risk of AV reintervention.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38442916

RESUMO

BACKGROUND: As redo surgical aortic valve replacement (AVR) is relatively high risk, valve-in-valve transcatheter AVR has emerged as an alternative for failed prostheses. However, the majority of studies are outdated. This study assessed the current clinical outcomes of redo AVR. METHODS AND RESULTS: This study enrolled 324 patients who underwent redo AVR due to prosthetic valve failure from 2010 to 2021 in four tertiary centers. The primary outcome was operative mortality. The secondary outcomes were overall survival, cardiac death, and aortic valve-related events. Logistic regression analysis, clustered Cox proportional hazards models, and competing risk analysis were used to evaluate the independent risk factors. Redo AVR was performed in 242 patients without endocarditis and 82 patients with endocarditis. Overall operative mortality was 4.6% (15 deaths). Excluding patients with endocarditis, the operative mortality of redo AVR decreased to 2.5%. Multivariate analyses demonstrated that endocarditis (hazard ratio [HR]: 3.990, p = 0.014), longer cardiopulmonary bypass time (HR: 1.006, p = 0.037), and lower left ventricular ejection fraction (LVEF) (HR: 0.956, p = 0.034) were risk factors of operative mortality. Endocarditis and lower LVEF were independent predictors of overall survival. CONCLUSION: The relatively high risk of redo AVR was due to reoperation for prosthetic valve endocarditis. The outcomes of redo AVR for nonendocarditis are excellent. Our findings suggest that patients without endocarditis, especially with acceptable LVEF, can be treated safely with redo AVR.

6.
Molecules ; 29(2)2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38257395

RESUMO

Autophagy is a pivotal biological process responsible for maintaining the homeostasis of intracellular organelles. Yet the molecular intricacies of peroxisomal autophagy (pexophagy) remain largely elusive. From a ubiquitin-related chemical library for screening, we identified several inhibitors of the Von Hippel-Lindau (VHL) E3 ligase, including VH298, thereby serving as potent inducers of pexophagy. In this study, we observed that VH298 stimulates peroxisomal degradation by ATG5 dependently and escalates the ubiquitination of the peroxisomal membrane protein ABCD3. Interestingly, the ablation of NBR1 is similar to the curtailed peroxisomal degradation in VH298-treated cells. We also found that the pexophagy induced by VH298 is impeded upon the suppression of gene expression by the translation inhibitor cycloheximide. Beyond VHL inhibition, we discovered that roxadustat, a direct inhibitor of HIF-α prolyl hydroxylase, is also a potent inducer of pexophagy. Furthermore, we found that VH298-mediated pexophagy is blocked by silencing HIF-1α. In conclusion, our findings suggest that VH298 promotes pexophagy by modulating VHL-mediated HIF-α transcriptional activity.


Assuntos
Autofagia , Ciclopropanos , Macroautofagia , Pirrolidinas , Tiazóis , Humanos , Células HeLa , Homeostase , Proteína Supressora de Tumor Von Hippel-Lindau/genética
7.
Artigo em Inglês | MEDLINE | ID: mdl-38237763

RESUMO

OBJECTIVE: The aim of the study was to elucidate the long-term outcomes of atrial fibrillation surgery in patients with atrial fibrillation and mitral valve disease by comparing the patients who underwent mitral valve surgery with and without atrial fibrillation surgery. METHODS: Between 2005 and 2017, 2680 patients with atrial fibrillation who underwent mitral valve surgery (mitral valve surgery with atrial fibrillation surgery, n = 1841; mitral valve surgery without atrial fibrillation surgery, n = 839) at 5 centers were included. After propensity score matching, 1442 patients were extracted (atrial fibrillation surgery group, n = 721; non-atrial fibrillation surgery group, n = 721). All-cause mortality, cardiac mortality, major adverse cardiac and cerebrovascular events, stroke or transient ischemic attack, and permanent pacemaker implantation were compared between the atrial fibrillation surgery and non-atrial fibrillation surgery groups. RESULTS: Overall survivals at 5 and 10 years postoperatively were 91.0% and 80.7% in the atrial fibrillation surgery group and 86.5% and 75.9% in the non-atrial fibrillation surgery group, respectively (P = .013). Cardiac mortality-free survivals at 5 and 10 years postoperatively were 96.9% and 91.7% in the atrial fibrillation surgery group and 90.9% and 83.7% in the non-atrial fibrillation surgery group, respectively (P < .001). Cumulative incidence of reoperation, major adverse cardiac and cerebrovascular events, and stroke or transient ischemic attack was lower in the matched atrial fibrillation surgery group compared with the matched non-atrial fibrillation surgery group up to 15 years postoperatively (P = .010, P < .001, and P = .012, respectively). Cumulative incidence of permanent pacemaker implantation was higher in the matched atrial fibrillation surgery group compared with the matched non-atrial fibrillation surgery group (P < .001). CONCLUSIONS: In patients with atrial fibrillation and mitral valve disease, mitral valve surgery concomitant with atrial fibrillation surgery was associated with lower mortality, cardiac mortality, major adverse cardiac and cerebrovascular events, and stroke or transient ischemic attack up to 15 years after surgery when compared with mitral valve surgery without atrial fibrillation surgery.

9.
J Thorac Cardiovasc Surg ; 167(1): 116-126.e1, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-35248358

RESUMO

OBJECTIVES: The study objective was to evaluate the clinical implication of left ventricular diastolic dysfunction in patients with chronic severe aortic regurgitation undergoing aortic valve replacement. METHODS: We reviewed the medical records of 323 patients (age, 56.3 ± 14.1 years; 111 female) who underwent aortic valve replacement for chronic severe aortic regurgitation between 2005 and 2019. Left ventricular diastolic dysfunction was assessed by the ratio of peak left ventricular inflow velocity over mitral annular velocity (E/e'). The study end point was the composite of death and heart failure requiring hospital admission. RESULTS: The E/e' ratio was significantly correlated with age, left atrial dimension, left ventricular end-diastolic volume, mitral regurgitation grade, and tricuspid regurgitation grade (all P < .001). During follow-up (1748.3 patient-years), death and heart failure occurred in 36 patients (2.06/patient-year) and 9 patients (0.53/patient-year), respectively. In multivariable analysis, E/e' ratio (per 5 increment, hazard ratio, 1.32; 95% confidence interval, 1.02-1.71; P = .03), age (hazard ratio, 1.06; 95% confidence interval, 1.03-1.10; P < .001), and left ventricular ejection fraction (hazard ratio, 0.94; 95% confidence interval, 0.90-0.98; P = .002) were independent predictors of death and heart failure. The 5-year heart failure-free survival was 94.9% ± 1.7% in patients with E/e' less than 15% and 84.2% ± 4.2% in patients with E/e' 15 or greater (P < .001). CONCLUSIONS: The E/e' ratio was significantly associated with adverse outcomes in patients with chronic severe aortic regurgitation undergoing aortic valve replacement and may be useful as a prognostic marker in such patients.


Assuntos
Insuficiência da Valva Aórtica , Insuficiência Cardíaca , Disfunção Ventricular Esquerda , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Prognóstico , Insuficiência da Valva Aórtica/complicações , Insuficiência da Valva Aórtica/diagnóstico por imagem , Insuficiência da Valva Aórtica/cirurgia , Volume Sistólico , Função Ventricular Esquerda , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/etiologia
10.
J Chest Surg ; 56(6): 371-373, 2023 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-37915288
11.
Artigo em Inglês | MEDLINE | ID: mdl-37931797

RESUMO

OBJECTIVE: To compare the clinical outcomes of aortic valve replacement (AVR) using bovine pericardial and porcine bioprostheses, utilizing a nationwide administrative claims database. METHODS: Adult patients (age ≥40 years) who underwent bioprosthetic AVR, without other valve replacements, between 2003 and 2018 were identified from the Korean National Health Insurance Service database. The outcomes of interest were all-cause mortality, cardiac mortality, and valve-related events, including the incidence of reoperation, endocarditis, systemic thromboembolism, and major bleeding. Baseline adjustment was performed using propensity score matching. Time-related outcomes were evaluated using a competing risk analysis, with death as a competing risk. RESULTS: Among the 7714 patients who underwent bioprosthetic AVR, 5621 (72.9%) received bovine pericardial prostheses and 2093 (27.1%) received porcine bioprostheses. After matching, 1937 pairs were included in the final analysis. During follow-up (median, 4.49 years; interquartile range, 2.83-8.20 years), the use of porcine bioprostheses was associated with a higher risk of aortic valve reoperation (adjusted hazard ratio [HR], 1.87; 95% confidence interval [CI], 1.16 to 3.01); however, no significant differences were observed in cumulative incidences of all-cause mortality, cardiac mortality, thromboembolism, or major bleeding. Subgroup analyses revealed that the use of bovine valves was associated with improved survival in patients with diabetes mellitus, whereas in patients undergoing dialysis, porcine valves exhibited better survival than bovine valves. CONCLUSIONS: In this large nationwide cohort study of patients undergoing bioprosthetic aortic valve replacement, the use of porcine prostheses was significantly associated with an increased risk of reoperation compared with the use of bovine prostheses, supporting previous findings.

12.
JTCVS Open ; 15: 27-37, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37808051

RESUMO

Objective: Genetic aortopathy, if left untreated, leads to aortic catastrophe in most affected individuals. We sought to determine the genetic mutation patterns and detection rates in patients with aortopathy and their families with a systematic screening protocol. Methods: In 2016 to 2020, patients with aortic dissection or root aneurysm (Z score ≥2) and their first-degree relatives were enrolled in a prospective registry at a tertiary referral center. The individuals underwent systematic single- or multi-gene panel testing depending on clinical presentations. Results: Among 575 enrolled individuals (mean age, 46.6 ± 14.5 years; 203 women), 346 (60.2%) underwent genetic testing. Rates of relevant gene mutations identified were 39.4% (91/231), 27.1% (54/199) and 72.4% (n = 105) in aneurysm, dissection, and family screening groups, respectively (P < .001). Mutated genes frequently identified were FBN1 (n = 199; Marfan), TGFBR1/2 or SMAD3 (n = 14; Loeys-Dietz), COL3A1/COL5A2 (n = 15; Ehlers-Danlos), and ACTA2 (n = 10). After enrollment, 123 aortic surgeries were performed in 117 patients (20.3%) including 15 family members, with resultant operative mortality of 0.8% (n = 1). In logistic regression analysis, systemic score in Ghent nosology was the only significant factor associated with positive gene mutation (odds ratio, 14.81; 95% confidence interval, 6.87-31.96), and its 3.5 point cutoff showed the best predictive value with 78.2% sensitivity and 87.2% specificity. Conclusions: Genetic aortopathy was identified in a considerable proportion of patients with aortopathy and their family members by systematic genetic testing. This strategy is recommended for timely diagnosis and proactive management of genetic aortopathy.

13.
JTCVS Open ; 15: 16-24, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37808063

RESUMO

Objective: To investigate the association between false lumen (FL) dependency of segmental arteries (SAs) at T9-L3 levels and the risk of spinal cord injury (SCI) following total arch replacement and frozen elephant trunk (FET) implantation in the setting of acute DeBakey type I aortic dissection (AAD). Methods: The study involved consecutive patients with AAD who underwent total arch replacement and FET implantation between 2020 and 2022. Primary outcome was postoperative SCI. The inverse probability of treatment weighting (IPTW) method was employed to minimize the impact of no-randomization bias. Antegrade placement of FET was followed by end-to-end anastomosis of a 4-branch arch graft at the proximal landing site of FET. Results: A total of 146 patients were included (age, 50.5 ± 11.7 years, 115 male), of whom 35 (24%) had SAs at T9-L3 levels completely dependent on FL (FL-dependency group). There was no significant difference in early (30-day or in-hospital) mortality rates between FL-dependency (14.3%) and FL-independency (18.0%) groups (P = .80), however, the rate of SCI was significantly higher in the FL-Dependency group (34.3% vs 2.7%, P < .001). After adjustments, FL dependency was associated with a significantly increased risk of SCI (odds ratio, 13.1; 95% confidence interval, 4.2-41.0; P < .001), whereas it was not significantly associated with risks of early mortality or other major complications (P = .16-.98). Conclusions: FL dependency of SAs at the T9-L3 levels was significantly associated with the development of SCI following FET implantation in AAD, warning against its uses on patients presenting with FL dependency of SAs at critical segments.

15.
Korean Circ J ; 53(8): 550-562, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37525492

RESUMO

BACKGROUND AND OBJECTIVES: To identify the factors associated with adverse outcomes following surgery for functional insufficiency of the mitral valve (MV) or tricuspid valve (TV) associated with atrial fibrillation (AF). METHODS: We evaluated 100 patients (age, 66.5±10.0 years; 47 males) who consecutively underwent surgery for functional insufficiency of the MV or TV associated with AF between January 2000 and December 2020 at our center. The primary outcome was a composite endpoint of all-cause death, valve reoperation, congestive heart failure (CHF) requiring rehospitalization, and stroke. RESULTS: During follow-up (532 patients-years [PYs]), adverse events included death in 16 (3.0%/yr), MV reoperation in 1 (0.2%/yr), CHF in 14 (2.6%/yr), and stroke in 5 (0.9%/yr) patients, demonstrating a 5-year rate of freedom from the primary endpoint of 69.5%. The rate of postoperative AF was high even in those who underwent AF ablation (n=92), with cumulative rates of 48.1% at 1 year and 60.2% at 5 years. In multivariable analyses, the primary outcome was significantly associated with age (adjusted hazard ratio [aHR], 1.06; 95% confidence interval [CI], 1.02-1.10; p=0.005), chronic kidney disease (aHR, 7.76; 95% CI, 2.28-26.38; p=0.001), left atrial appendage exclusion (aHR, 0.35; 95% CI, 0.16-1.78; p=0.010), and postoperative AF as a time-varying covariate (aHR, 3.33; 95% CI, 1.50-7.40; p=0.003). CONCLUSION: Among patients undergoing surgery for functional atrioventricular insufficiency associated with AF, a significant proportion showed recurrence of AF over time after concomitant AF ablation, which was significantly associated with poor clinical outcomes.

16.
JTCVS Tech ; 20: 1-9, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37555043

RESUMO

Objectives: Paraplegia is a distressing complication after open thoracoabdominal aortic aneurysm (TAAA) repair, and revascularization of T8-L2-level segmental arteries is considered pivotal to prevent paraplegia. We employed 3-dimensional (3D) printing to efficiently revascularize segmental/visceral arteries and prospectively evaluated its safety and efficacy. Methods: From January 1, 2020, to June 30, 2022, we prospectively enrolled patients of extent I, II, or III TAAA repair. Guidance models were 3D-printed based on preoperative computed tomography, and multibranched aortic grafts were manually constructed upon this model before surgery. The composite outcome of operative mortality, permanent stroke, and permanent spinal cord deficit (SCD) was compared with the historical control group (n = 77, in 2015-2020), subjected to similar TAAA repair without 3D printing. Results: A total of 38 patients (58.6 ± 13.2 years) underwent open TAAA repair with the aid of 3D printing. Extent I, II, and III repairs were performed in 14 (36.8%), 17 (44.7%), and 7 (18.4%), respectively. Concomitant arch repair and bi-iliac reconstruction were performed in 7 (18.4%) and 6 patients (15.8%), respectively. Mean pump time was 107.7 ± 55.5 minutes. Operative mortality, permanent stroke, and permanent SCD each occurred in 1 patient (2.6%), and the incidence of the composite outcome was 7.9% (3/38). In the control group, mean pump time was 166.0 ± 83.9 minutes, significantly longer than the 3D-printing group (P < .001), and operative mortality, permanent stroke, permanent SCD, and the composite outcome occurred in 7 (9.1%), 9 (11.7%), 8 (10.4%), and 19 (24.7%), respectively. Conclusions: Open repairs of extensive TAAA with 3D printing showed favorable safety and efficacy, which need further validation by larger studies.

17.
Am J Cardiol ; 203: 81-91, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37481816

RESUMO

Although optimal medical therapy (OMT) after coronary revascularization is advocated for intensive secondary prevention, its criteria and effect on long-term outcomes are uncertain. Using data from the ASAN-Multivessel (Asan Medical Center-Multivessel Revascularization) registry, we identified 8,311 patients who underwent coronary artery bypass grafting (CABG) (n = 3,115) or percutaneous coronary intervention (PCI) (n = 5,196). OMT was defined as the combination of minimum of 3 medications in 4 drug classes (antiplatelet drugs, statins, ß blockers, and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers). Two primary outcomes were all-cause mortality and serious composite outcome of death, spontaneous myocardial infarction, or stroke at 10 years. Of 8,311 patients, 4,321 (52.0%) followed OMT. In the 3,397 propensity-score-matched cohort, OMT status compared with non-OMT status was significantly associated with a lower risk of all-cause mortality (10.7% vs 18.7%; hazard ratio [HR] 0.55, 95% confidence interval [CI] 0.47 to 0.65) and serious composite outcome (14.5% vs 22.5%, HR 0.635, 95% CI 0.55 to 0.73) at 10 years. The association on 10-year mortality was more prominent in the PCI group (HR 0.45, 95% CI 0.36 to 0.56) than in the CABG group (HR 0.72, 95% CI 0.58 to 0.90) with a significant interaction (p = 0.001). Overall findings were consistent using different OMT criteria (all 4 types of medications). In conclusion, OMT significantly lowered the risks of mortality and major cardiovascular events at 10 years in patients with multivessel revascularization. The OMT impact on mortality was more remarkable in the PCI group than in the CABG group. This work was registered at http://ClinicalTrials.gov (Identifier: NCT02039752).


Assuntos
Doença da Artéria Coronariana , Infarto do Miocárdio , Intervenção Coronária Percutânea , Humanos , Ponte de Artéria Coronária/efeitos adversos , Infarto do Miocárdio/etiologia , Revascularização Miocárdica , Intervenção Coronária Percutânea/efeitos adversos , Resultado do Tratamento
18.
Heart ; 109(19): 1479-1485, 2023 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-37290900

RESUMO

BACKGROUND: Some patients have severe aortic valve stenosis (AS) despite a lower degree of aortic valve calcification (AVC). This study compared the clinical features and prognosis of patients undergoing aortic valve replacement (AVR) for severe AS with a low AVC score compared with those with higher AVC scores. METHODS: This study included 1002 Korean patients with symptomatic severe degenerative AS who underwent AVR. We measured AVC score before AVR and defined low AVC as AVC score of <2000 units for male patients and <1300 units for female patients. Patients with bicuspid or rheumatic aortic valve disease were excluded. RESULTS: The mean age was 75.6±7.9 years and 487 patients (48.6%) were female. Mean left ventricular ejection fraction was 59.4%±10.4%, and concomitant coronary revascularisation was performed in 96 patients (9.6%). The median aortic valve calcium score was 3122 units (IQR 2249-4289 units) among male patients and 1756 units (IQR 1192-2572) among female patients. A total of 242 patients (24.2%) had low AVC; they were significantly younger (73.5±8.7 years vs 76.3±7.5 years, p<0.001) and were more likely to be female (59.5% vs 45.1%, p<0.001) and on haemodialysis (5.4% vs 1.8%, p=0.006) than those with high AVC. During a follow-up (median: 3.8 years), the patients with low AVC had significantly higher risk of death from any cause (adjusted HR 1.60, 95% CI 1.02 to 2.52, p=0.04), mostly non-cardiac cause. CONCLUSIONS: Patients with low AVC exhibit distinct clinical characteristics and a higher risk of long-term mortality compared with those with high AVC.


Assuntos
Estenose da Valva Aórtica , Valva Aórtica , Humanos , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Cálcio , Constrição Patológica/complicações , Volume Sistólico , Função Ventricular Esquerda , Estenose da Valva Aórtica/diagnóstico , Estenose da Valva Aórtica/cirurgia , Estenose da Valva Aórtica/complicações , Índice de Gravidade de Doença
19.
Mol Brain ; 16(1): 41, 2023 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-37170364

RESUMO

The primary cilium, an antenna-like structure on the cell surface, acts as a mechanical and chemical sensory organelle. Primary cilia play critical roles in sensing the extracellular environment to coordinate various developmental and homeostatic signaling pathways. Here, we showed that the depletion of heat shock protein family A member 9 (HSPA9)/mortalin stimulates primary ciliogenesis in SH-SY5Y cells. The downregulation of HSPA9 enhances mitochondrial stress by increasing mitochondrial fragmentation and mitochondrial reactive oxygen species (mtROS) generation. Notably, the inhibition of either mtROS production or mitochondrial fission significantly suppressed the increase in primary ciliogenesis in HSPA9-depleted cells. In addition, enhanced primary ciliogenesis contributed to cell survival by activating AKT in SH-SY5Y cells. The abrogation of ciliogenesis through the depletion of IFT88 potentiated neurotoxicity in HSPA9-knockdown cells. Furthermore, both caspase-3 activation and cell death were increased by MK-2206, an AKT inhibitor, in HSPA9-depleted cells. Taken together, our results suggest that enhanced primary ciliogenesis plays an important role in preventing neurotoxicity caused by the loss of HSPA9 in SH-SY5Y cells.


Assuntos
Neuroblastoma , Proteínas Proto-Oncogênicas c-akt , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Linhagem Celular Tumoral , Apoptose , Estresse Oxidativo , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas Mitocondriais/metabolismo
20.
JAMA Netw Open ; 6(5): e2314671, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-37213100

RESUMO

Importance: Although a patient's age may be the only objective figure that can be used as a reference indicator in selecting the type of prosthesis in heart valve surgery, different clinical guidelines use different age criteria. Objective: To explore the age-associated survival-hazard functions associated with prosthesis type in aortic valve replacement (AVR) and mitral valve replacement (MVR). Design, Setting, and Participants: This cohort study compared the long-term outcomes associated with mechanical and biologic prostheses in AVR and MVR according to recipient's age using a nationwide administrative data from the Korean National Health Insurance Service. To reduce the potential treatment-selection bias between mechanical and biologic prostheses, the inverse-probability-of-treatment-weighting method was used. Participants included patients who underwent AVR or MVR in Korea between 2003 and 2018. Statistical analysis was performed between March 2022 and March 2023. Exposures: AVR, MVR, or both AVR and MVR with mechanical or biologic prosthesis. Main Outcomes and Measures: The primary end point was all-cause mortality after receiving prosthetic valves. The secondary end points were the valve-related events, including the incidence of reoperation, systemic thromboembolism, and major bleeding. Results: Of the total of 24 347 patients (mean [SD] age, 62.5 [7.3] years; 11 947 [49.1%] men) included in this study, 11 993 received AVR, 8911 received MVR, and 3470 received both AVR and MVR simultaneously. Following AVR, bioprosthesis was associated with significantly greater risks of mortality than mechanical prosthesis in patients younger than 55 years (adjusted hazard ratio [aHR], 2.18; 95% CI, 1.32-3.63; P = .002) and in those aged 55 to 64 years (aHR, 1.29; 95% CI, 1.02-1.63; P = .04), but the risk of mortality reversed in patients aged 65 years or older (aHR, 0.77; 95% CI, 0.66-0.90; P = .001). For MVR, the risk of mortality was also greater with bioprosthesis in patients aged 55 to 69 years (aHR, 1.22; 95% CI, 1.04-1.44; P = .02), but there was no difference for patients aged 70 years or older (aHR, 1.06; 95% CI, 0.79-1.42; P = .69). The risk of reoperation was consistently higher with bioprosthesis, regardless of valve position, in all age strata (eg, MVR among patients aged 55-69 years: aHR, 7.75; 95% CI, 5.14-11.69; P < .001); however, the risks of thromboembolism and bleeding were higher in patients aged 65 years and older after mechanical AVR (thromboembolism: aHR, 0.55; 95% CI, 0.41-0.73; P < .001; bleeding: aHR, 0.39; 95% CI, 0.25-0.60; P < .001), with no differences after MVR in any age strata. Conclusions and Relevance: In this nationwide cohort study, the long-term survival benefit associated with mechanical prosthesis vs bioprosthesis persisted until age 65 years in AVR and age 70 years in MVR.


Assuntos
Produtos Biológicos , Doenças das Valvas Cardíacas , Implante de Prótese de Valva Cardíaca , Próteses Valvulares Cardíacas , Tromboembolia , Masculino , Humanos , Pessoa de Meia-Idade , Feminino , Doenças das Valvas Cardíacas/epidemiologia , Doenças das Valvas Cardíacas/cirurgia , Valva Mitral/cirurgia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Estudos de Coortes , Próteses Valvulares Cardíacas/efeitos adversos , Tromboembolia/etiologia , Hemorragia/etiologia , República da Coreia/epidemiologia
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