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Primary cilia are crucial for cellular balance, serving as sensors for external conditions. Nephronophthisis and related ciliopathies, which are hereditary and degenerative, stem from genetic mutations in cilia-related genes. However, the precise mechanisms of these conditions are still not fully understood. Our research demonstrates that downregulating PDIA6, leading to cilia removal, makes cells more sensitive to ferroptotic death caused by endoplasmic reticulum (ER) stress. The reduction of PDIA6 intensifies the ER stress response, while also impairing the regulation of primary cilia in various cell types. PDIA6 loss worsens ER stress, hastening ferroptotic death in proximal tubule epithelial cells, HK2 cells. Counteracting this ER stress can mitigate PDIA6 depletion effects, restoring both the number and length of cilia. Moreover, preventing ferroptosis corrects the disrupted primary ciliogenesis due to PDIA6 depletion in HK2 cells. Our findings emphasize the role of PDIA6 in primary ciliogenesis, and suggest its absence enhances ER stress and ferroptosis. These insights offer new therapeutic avenues for treating nephronophthisis and similar ciliopathies.
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First described more than 350 years ago, infective endocarditis represents a global health concern characterised by infections affecting the native or prosthetic heart valves, the mural endocardium, a septal defect, or an indwelling cardiac device. Over recent decades, shifts in causation and epidemiology have been observed. Echocardiography remains pivotal in the diagnosis of infective endocarditis, with alternative imaging modalities gaining significance. Multidisciplinary management requiring expertise of cardiologists, cardiovascular surgeons, infectious disease specialists, microbiologists, radiologists and neurologists, is imperative. Current recommendations for clinical management often rely on observational studies, given the limited number of well conducted randomised controlled trials studying infective endocarditis due to the rarity of the disease. In this Seminar, we provide a comprehensive overview of optimal clinical practices in infective endocarditis, highlighting key aspects of pathophysiology, pathogens, diagnosis, management, prevention, and multidisciplinary approaches, providing updates on recent research findings and addressing remaining controversies in diagnostic accuracy, prevention strategies, and optimal treatment.
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Endocarditis , Humanos , Endocarditis/diagnóstico , Endocarditis/terapia , Endocarditis/epidemiología , Ecocardiografía , Antibacterianos/uso terapéuticoRESUMEN
OBJECTIVES: The optimal technique for repairing posterior mitral valve leaflet prolapse remains undetermined. We aimed to compare leaflet resection and neochordae implantation in patients undergoing mitral valve repair for posterior leaflet prolapse, focusing on transmitral pressure gradient and recurrence of mitral regurgitation. METHODS: We enrolled patients undergoing mitral valve repair using either leaflet resection or neochordae implantation for single-segment prolapse of posterior mitral valve leaflet between 2000 and 2021 at our institution. Longitudinal outcomes were evaluated after adjustments with inverse-probability-of-treatment weighting. Repeat echocardiographic measurements (n = 3473, 5.4/patient) of transmitral pressure gradient and significant (moderate or severe) mitral regurgitation recurrence were estimated using nonlinear mixed-effect models. Subgroup analyses were conducted based on the size and type of prosthesis. RESULTS: Among 639 patients, leaflet resection was used in 479 (75.0%) and neochordae implantation was used in 160 (25.0%). In the inverse-probability-of-treatment weighting adjusted cohort, the risk of death (P = .623) and mitral valve reoperation (P = .340) did not significantly differ between the 2 groups during a median follow-up of 97.3 months. Echocardiographic data showed comparable mean (at 5 years, 3.8 vs 4.0 mm Hg; P = .442) and peak (9.6 vs 10.4 mm Hg; P = .131) pressure gradients between groups, which persisted in most subgroup analyses. However, neochordae implantation was associated with a higher probability of significant mitral regurgitation recurrence compared with leaflet resection (at 5 years, 16.1% vs 7.0%; P < .001). CONCLUSIONS: Leaflet resection yielded similar clinical outcomes and transmitral pressure gradients compared with neochordae implantation after mitral valve repair, with a lower mitral regurgitation recurrence rate. These findings underscore the need to reassess the efficacy of neochordae implantation relative to leaflet resection.
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Objective: To investigate the effect of graft sizing on valve performance in valve-sparing aortic root replacement for bicuspid aortic valve. Methods: In addition to a diseased control model, 3 representative groups-free-edge length to aortic/graft diameter (FELAD) ratio <1.3, 1.5 to 1.64, and >1.7-were replicated in explanted porcine aortic roots (n = 3) using straight grafts sized respective to the native free-edge length. They were run on a validated ex vivo univentricular system under physiological parameters for 20 cycles. All groups were tested within the same aortic root to minimize inter-root differences. Outcomes included transvalvular gradient, regurgitation fraction, and orifice area. Linear mixed effects model and pairwise comparisons were employed to compare outcomes across groups. Results: The diseased control had mean transvalvular gradient 10.9 ± 6.30 mm Hg, regurgitation fraction 32.5 ± 4.91%, and orifice area 1.52 ± 0.12 cm2. In ex vivo analysis, all repair groups had improved regurgitation compared with control (P < .001). FELAD <1.3 had the greatest amount of regurgitation among the repair groups (P < .001) and 1.5-1.64 the least (P < .001). FELAD <1.3 and >1.7 exhibited greater mean gradient compared with both control and 1.5 to 1.64 (P < .001). Among the repair groups, 1.5 to 1.64 had the largest orifice area, and >1.7 the smallest (P < .001). Conclusions: For a symmetric bicuspid aortic valve, performance after valve-sparing aortic root replacement shows a bimodal distribution across graft size. As the FELAD ratio departs from 1.5 to 1.64 in either direction, significant increases in transvalvular gradient are observed. FELAD <1.3 may also result in suboptimal improvement of baseline regurgitation.
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Objective: Open arch repair is perceived as a challenging, high-risk procedure, with a barrier against the use of a minimally invasive approach. We aimed to present a mini-access total arch replacement performed by stratified approaches and to evaluate perioperative outcomes to contribute to the body of evidence. Methods: We evaluated 40 consecutive patients (aged 69.5 years; interquartile range, 65.6-76.3 years) undergoing elective total arch replacement using 5- to 8-cm upper mini-sternotomy between 2018 and 2022. Surgical strategies, including arterial inflow site and methods of branching vessel reconstruction, were systematically selected at the individual level. To evaluate comparative outcomes, contemporary cases undergoing total arch replacement via sternotomy with similar eligibility criteria served as a control group, and the inverse-treatment-weighting method was used to adjust for baseline characteristics. Results: Arch-first anastomosis using trifurcate graft, distal-first anastomosis using 4-branch graft, and island anastomosis were used in 18 (45%), 12 (30.0%), and 10 (25%) patients, respectively. Lower body and cardiac ischemic times were 23.4 minutes (interquartile range, 18.0-29.0 minutes) and 66.7 minutes (interquartile range, 50.1-78.2 minutes). There was no early (30-day or in-hospital) mortality, and 2 patients experienced disabling stroke (5.0%). The contemporary control group comprised 55 patients. After an adjustment, a mini-access group showed lower risks of stroke (odds ratio, 0.88; 95% CI, 0.78-1.00; P = .049) and a composite of major complications (odds ratio, 0.79; 95% CI, 0.68-0.92; P = .003), compared with a sternotomy approach. Conclusions: Based on present results, mini-access total arch replacement may be performed with reasonable safety and efficiency.
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Objectives: Mid-aortic syndrome is a rare condition characterized by severe aortic narrowing, leading to high upper body blood pressure and organ hypoperfusion, necessitating surgical intervention. Although central bypassing is considered ideal, it involves extensive incisions. To overcome these limitations, less-invasive approaches have been developed. This study aims to introduce a mini-access approach using video-endoscopy and to evaluate the feasibility and outcomes of mini-access ascending aorto-bifemoral bypass surgery. Methods: From November 2020 to May 2022, we performed ascending aorta to bifemoral artery bypass operations on 7 patients to treat steno-occlusive diseases in the downstream aorta. A Y-graft was created, and procedures were conducted under general anesthesia using video-endoscopy with limited skin incisions. Results: Intraoperatively, there were no major complications, and none of the patients required cardiopulmonary bypass support. Furthermore, there were no postoperative mortalities or major complications. Postoperatively, the mean ankle-brachial index significantly improved from 0.59/0.59 to 0.96/0.92 (P = .004), and the mean glomerular filtration rate increased from 61.1 to 85.3 mL/min/1.73 mm2 (P = .012). Additionally, symptoms of claudication resolved in all patients. Conclusions: Videoscope-assisted mini-access aortic bypass surgery not only provides favorable early postoperative outcomes but also represents a technically feasible alternative to traditional surgical approaches for the treatment of steno-occlusive aortic diseases.
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BACKGROUND: The operative outcomes of thoracoabdominal aortic aneurysms (TAAAs) are challenged by high operative mortality and disabling complications. This study aimed to explore the baseline clinical, anatomical, and procedural risk factors that impact early and late outcomes following open repair of TAAAs. METHODS: We reviewed the medical records of 290 patients who underwent open repair of TAAAs between 1992 and 2020 at a tertiary referral center. Determinants of early mortality (within 30 days or in hospital) were analyzed using multivariable logistic regression models, while those of overall follow-up mortality were explored using multivariable Cox proportional hazards models and landmark analyses. RESULTS: The rates of early mortality and spinal cord deficits were 13.1% and 11.0%, respectively, with Crawford extent II showing the highest rates. In the logistic regression models, older age (P < 0.001), high cardiopulmonary bypass (CPB) time (P < 0.001), and low surgical volume of the surgeon (P < 0.001) emerged as independent factors significantly associated with early mortality. During follow-up (median, 5.0 years; interquartile range, 1.1-7.6 years), 82 late deaths occurred (5.7%/patient-year). Cox proportional hazards models demonstrated that older age (P < 0.001) and low hemoglobin level (P = 0.032) were significant risk factors of overall mortality, while the landmark analyses revealed that the significant impacts of low surgical volume (P = 0.017), high CPB time (P = 0.002), and Crawford extent II (P = 0.017) on mortality only remained in the early postoperative period, without significant late impacts (all P > 0.05). CONCLUSION: There were differential temporal impacts of perioperative risk variables on mortality in open repair of TAAAs, with older age and low hemoglobin level having significant impacts throughout the postoperative period, and low surgical volume, high CPB time, and Crawford extent II having impacts in the early postoperative phase.
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Aneurisma de la Aorta Torácica , Complicaciones Posoperatorias , Humanos , Masculino , Femenino , Estudios Retrospectivos , Aneurisma de la Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/mortalidad , Persona de Mediana Edad , Factores de Riesgo , Anciano , Complicaciones Posoperatorias/mortalidad , Complicaciones Posoperatorias/epidemiología , Implantación de Prótesis Vascular/mortalidad , Implantación de Prótesis Vascular/efectos adversos , Implantación de Prótesis Vascular/métodos , Factores de Tiempo , Mortalidad Hospitalaria , Aorta Torácica/cirugíaRESUMEN
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 three 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% male), 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 three 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.
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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.
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Procedimientos Quirúrgicos Cardíacos , Trasplante de Órganos , Humanos , Estudios Retrospectivos , Receptores de Trasplantes , Análisis por Apareamiento , Complicaciones Posoperatorias/etiología , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Trasplante de Órganos/efectos adversosRESUMEN
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.
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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.
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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.
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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.
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Autofagia , Ciclopropanos , Macroautofagia , Pirrolidinas , Tiazoles , Humanos , Células HeLa , Homeostasis , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/genéticaRESUMEN
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.
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Insuficiencia de la Válvula Aórtica , Insuficiencia Cardíaca , Disfunción Ventricular Izquierda , Humanos , Femenino , Adulto , Persona de Mediana Edad , Anciano , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Pronóstico , Insuficiencia de la Válvula Aórtica/complicaciones , Insuficiencia de la Válvula Aórtica/diagnóstico por imagen , Insuficiencia de la Válvula Aórtica/cirugía , Volumen Sistólico , Función Ventricular Izquierda , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/etiologíaRESUMEN
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.