Outcomes following heart valve surgery in patients with infective endocarditis and preoperative septic cerebral embolism: Insights from the Multicenter Project of Analysis of Infective Endocarditis in Germany (CAMPAIGN) Registry.

OBJECTIVES: This study aimed to analyze the impact of preoperative septic cerebral embolism on early and late postoperative outcomes in patients with infective endocarditis (IE) undergoing valve surgery. METHODS: Retrospective multicentric study based on the Clinical Multicentric Project for Analysis of Infective Endocarditis in Germany (CAMPAIGN) registry comprising patients with IE who underwent valve surgery between 1994 and 2018 at six German centers. Patients were divided into two groups for statistical comparison according to the presence or absence of preoperative septic cerebral embolism. Propensity score matching was performed for adjusted comparisons of postoperative outcomes. Primary outcomes were 30-day mortality and estimated 5-year survival. RESULTS: A total of 4917 patients were included in the analysis, 3909 (79.5%) patients without and 1008 (20.5%) patients with preoperative septic cerebral embolism. Patients with preoperative septic cerebral embolism had more baseline comorbidities. Mitral valve endocarditis (44.1% vs. 33.0% p < 0.001), large vegetations >10mm (43.1% vs. 30.0%,p<0.001), and Staphylococcus species infection (42.3% vs. 21.3%, p < 0.001) were more frequent in the cerebral embolism group. Among patients with preoperative cerebral embolism, 286 (28.4%) patients had no stroke signs (silent stroke). After matching (1008 matched pairs), there was no statistically significant difference in 30-day mortality (20.1%. vs. 22.8%; p = 0.14) and 5-year survival (47.8% vs. 49.1%; stratified log-rank p = 0.77) in patients with and without preoperative cerebral embolism, respectively. CONCLUSION: Preoperative septic cerebral embolism in patients with infective endocarditis requiring valve surgery does not negatively affect early or late mortality, therefore, it should not play a major role in deciding if surgery is to be performed.

Failure of Surgical Aortic Valve Prostheses: An Analysis of Heart Team Decisions and Postoperative Outcomes.

Objectives: To analyze Heart Team decisions and outcomes following failure of surgical aortic valve replacement (SAVR) prostheses. Methods: Patients undergoing re-operations following index SAVR (Redo-SAVR) and those undergoing valve-in-valve transcatheter aortic valve replacement (ViV-TAVR) following SAVR were included in this study. Patients who underwent index SAVR and/or Redo-SAVR for endocarditis were excluded. Data are presented as medians and 25th-75th percentiles, or absolute numbers and percentages. Outcomes were analyzed in accordance to the VARC-3 criteria. Results: Between 01/2015 and 03/2021, 53 patients underwent Redo-SAVR, 103 patients ViV-TAVR. Mean EuroSCORE II was 5.7% (3.5-8.5) in the Redo-SAVR group and 9.2% (5.4-13.6) in the ViV group. In the Redo-SAVR group, 12 patients received aortic root enlargement (22.6%). Length of hospital and ICU stay was longer in the Redo-SAVR group (p < 0.001; p < 0.001), PGmax and PGmean were lower in the Redo-SAVR group as compared to the ViV-TAVR group (18 mmHg (10-30) vs. 26 mmHg (19-38), p < 0.001) (9 mmHg (6-15) vs. 15 mmHg (9-21), p < 0.001). A higher rate of paravalvular leakage was seen in the ViV-TAVR group (p = 0.013). VARC-3 Early Safety were comparable between the two populations (p = 0.343). Survival at 1 year and 5 years was 82% and 36% in the ViV-TAVR cohort and 84% and 77% in the Redo-SAVR cohort. The variables were patient age (OR 1.061; [95% CI 1.020-1.104], p = 0.004), coronary heart disease (OR 2.648; [95% CI 1.160-6.048], p = 0.021), and chronic renal insufficiency (OR 2.711; [95% CI 1.160-6.048], p = 0.021) showed a significant correlation to ViV-TAVR. Conclusions: Heart Team decisions are crucial in the treatment of patients with degenerated aortic bioprostheses and lead to a low mortality in both treatment paths thanks to patient-specific therapy planning. ViV-TAVR offers a treatment for elderly or intermediate-risk profile patients with comparable short-term mortality. However, this therapy is associated with increased pressure gradients and a high prevalence of paravalvular leakage. Redo-SAVR enables the surgical treatment of concomitant cardiac pathologies and allows anticipation for later VIV-TAVR by implanting the largest possible valve prostheses.

Infective endocarditis and spondylodiscitis-impact of sequence of surgical therapy on survival and recurrence rate.

OBJECTIVES: To date, there are no standardized treatment algorithms or recommendations for patients with infective endocarditis (IE) and concomitant spondylodiscitis (SD). Therefore, our aim was to analyse whether the sequence of surgical treatment of IE and SD has an impact on postoperative outcome and to identify risk factors for survival and postoperative recurrence. METHODS: Patients with IE underwent surgery in 4 German university hospitals between 1994 and 2022. Univariable and multivariable analyses were performed to identify possible predictors of 30-day/1-year mortality and recurrence of IE and/or SD. RESULTS: From the total IE cohort (n = 3991), 150 patients (4.4%) had concomitant SD. Primary surgery for IE was performed in 76.6%, and primary surgery for SD in 23.3%. The median age was 70.0 (64.0-75.6) years and patients were mostly male (79.5%). The most common pathogens detected were enterococci and Staphylococcus aureus followed by streptococci, and coagulase-negative Staphylococci. If SD was operated on first, 30-day mortality was significantly higher than if IE was operated on 1st (25.7% vs 11.4%; P = 0.037) and we observed a tendency for a higher 1-year mortality. If IE was treated 1st, we observed a higher recurrence rate within 1 year (12.2% vs 0%; P = 0.023). Multivariable analysis showed that primary surgery for SD was an independent predictor of 30-day mortality. CONCLUSIONS: Primary surgical treatment for SD was an independent risk factor for 30-day mortality. When IE was treated surgically 1st, the recurrence rate of IE and/or SD was higher.

Sex-related differences in patients with infective endocarditis requiring cardiac surgery: insights from the CAMPAIGN Study Group.

OBJECTIVES: Sex-related differences play a role in cardiovascular disease-related outcomes. There is, however, a knowledge gap regarding sex-specific differences in patients with infective endocarditis (IE)-requiring surgical treatment. This study aims to analyse sex-related differences in the clinical presentation, treatment and clinical outcomes of patients with IE-requiring surgical treatment from the multicentric Germany-wide CAMPAIGN registry. METHODS: Patients with IE who underwent cardiac surgery between 1994 and 2018 at six German centres were retrospectively analysed. Outcomes were compared based on patients' sex. Primary outcomes were 30-day mortality and mid-term survival. RESULTS: A total of 4917 patients were included in the analysis (1364 female [27.7%] and 3553 male [72.3%]). Female patients presented with more comorbidities and higher surgical risk (EuroScore II 12.0% vs 10.0%, P < 0.001). The early postoperative course of female patients was characterized by longer ventilation times (20.0 h vs 16.0 h; P = 0.004), longer intensive care unit stay (4.0 days vs 3.0 days; P < 0.001), and more frequent new-onset dialysis (265 [20.3%] vs 549 [16.3%]; P = 0.001). The 30-day mortality was 13.8% and 15.5% in female and male patients, respectively (P = 0.06). The estimated mid-term survival was significantly higher amongst male patients (56.1% vs 45.4%; Log-rank P < 0.001). Female sex was an independent predictor of mid-term mortality (HR 1.2 [95% CI 1.0-1.4], P = 0.01). CONCLUSIONS: Male patients more frequently undergo cardiac surgery for IE. However, female patients have a higher surgical risk profile and subsequently an increased early postoperative morbidity, but with similar 30-day mortality compared with male patients. The estimated mid-term survival is lower amongst female patients.

Transcatheter heart valve explant with infective endocarditis-associated prosthesis failure and outcomes: the EXPLANT-TAVR international registry.

BACKGROUND AND AIMS: Surgical explantation of transcatheter heart valves (THVs) is rapidly increasing, but there are limited data on patients with THV-associated infective endocarditis (IE). This study aims to assess the outcomes of patients undergoing THV explant for IE. METHODS: All patients who underwent THV explant between 2011 and 2022 from 44 sites in the EXPLANT-TAVR registry were identified. Patients with IE as the reason for THV explant were compared to those with other mechanisms of bioprosthetic valve dysfunction (BVD). RESULTS: A total of 372 patients from the EXPLANT-TAVR registry were included. Among them, 184 (49.5%) patients underwent THV explant due to IE and 188 (50.5%) patients due to BVD. At the index transcatheter aortic valve replacement, patients undergoing THV explant for IE were older (74.3 ± 8.6 vs. 71 ± 10.6 years) and had a lower Society of Thoracic Surgeons risk score [2.6% (1.8-5.0) vs. 3.3% (2.1-5.6), P = .029] compared to patients with BVD. Compared to BVD, IE patients had longer intensive care unit and hospital stays (P < .05) and higher stroke rates at 30 days (8.6% vs. 2.9%, P = .032) and 1 year (16.2% vs. 5.2%, P = .010). Adjusted in-hospital, 30-day, and 1-year mortality was 12.1%, 16.1%, and 33.8%, respectively, for the entire cohort, with no significant differences between groups. Although mortality was numerically higher in IE patients 3 years postsurgery (29.6% for BVD vs. 43.9% for IE), Kaplan-Meier analysis showed no significant differences between groups (P = .16). CONCLUSIONS: In the EXPLANT-TAVR registry, patients undergoing THV explant for IE had higher 30-day and 1-year stroke rates and longer intensive care unit and hospital stays. Moreover, patients undergoing THV explant for IE had a higher 3-year mortality rate, which did not reach statistical significance given the relatively small sample size of this unique cohort and the reduced number of events.

A first comprehensive analysis of Transcribed Ultra Conserved Regions uncovers important regulatory functions of novel non-coding transcripts in gliomas.

Transcribed Ultra-Conserved Regions (TUCRs) represent a severely understudied class of putative non-coding RNAs (ncRNAs) that are 100% conserved across multiple species. We performed the first-ever analysis of TUCRs in glioblastoma (GBM) and low-grade gliomas (LGG). We leveraged large human datasets to identify the genomic locations, chromatin accessibility, transcription, differential expression, correlation with survival, and predicted functions of all 481 TUCRs, and identified TUCRs that are relevant to glioma biology. Of these, we investigated the expression, function, and mechanism of action of the most highly upregulated intergenic TUCR, uc.110, identifying it as a new oncogene. Uc.110 was highly overexpressed in GBM and LGG, where it promoted malignancy and tumor growth. Uc.110 activated the WNT pathway by upregulating the expression of membrane frizzled-related protein (MFRP), by sponging the tumor suppressor microRNA miR-544. This pioneering study shows important roles for TUCRs in gliomas and provides an extensive database and novel methods for future TUCR research.

Unraveling the Predictors for Delirium and ICU Stay Duration in Patients with Heart Failure and Reduced Ejection Fraction (HFrEF) Undergoing Coronary Artery Bypass Grafting-A Multicentric Analysis.

Objective: This study assesses predictors for postoperative delirium (POD) and ICU stay durations in HFrEF patients undergoing CABG, focusing on ONCAB versus OPCAB surgical methods. Summary Background Data: In cardiac surgery, especially CABG, POD significantly impacts patient recovery and healthcare resource utilization. With varying incidences based on surgical techniques, this study provides an in-depth analysis of POD in the context of HFrEF patients, a group particularly susceptible to this complication. Methods: A retrospective analysis of 572 patients who underwent isolated CABG surgery with a preoperative ejection fraction under 40% was conducted at four German university hospitals. Patients were categorized into ONCAB and OPCAB groups for comparative analysis. Results: Age and Euro Score II were significant predictors of POD. The ONCAB group showed higher incidences of re-sternotomy (OR: 3.37), ECLS requirement (OR: 2.29), and AKI (OR: 1.49), whereas OPCAB was associated with a lower incidence of delirium. Statistical analysis indicated a significant difference in ICU stay durations between the two groups, influenced by surgical complexity and postoperative complications. Conclusions: This study underscores the importance of surgical technique in determining postoperative outcomes in HFrEF patients undergoing CABG. OPCAB may offer advantages in reducing POD incidence. These findings suggest the need for tailored surgical decisions and comprehensive care strategies to enhance patient recovery and optimize healthcare resources.

A first comprehensive analysis of Transcribed Ultra Conserved Regions uncovers important regulatory functions of novel non-coding transcripts in gliomas.

Transcribed Ultra-Conserved Regions (TUCRs) represent a severely understudied class of putative non-coding RNAs (ncRNAs) that are 100% conserved across multiple species. We performed the first-ever analysis of TUCRs in glioblastoma (GBM) and low-grade gliomas (LGG). We leveraged large human datasets to identify the genomic locations, chromatin accessibility, transcription, differential expression, correlation with survival, and predicted functions of all 481 TUCRs, and identified TUCRs that are relevant to glioma biology. Of these, we investigated the expression, function, and mechanism of action of the most highly upregulated intergenic TUCR, uc.110, identifying it as a new oncogene. Uc.110 was highly overexpressed in GBM and LGG, where it promoted malignancy and tumor growth. Uc.110 activated the WNT pathway by upregulating the expression of membrane frizzled-related protein (MFRP), by sponging the tumor suppressor microRNA miR-544. This pioneering study shows important roles for TUCRs in gliomas and provides an extensive database and novel methods for future TUCR research.

Influence of Obesity on Short-Term Surgical Outcomes in HFrEF Patients Undergoing CABG: A Retrospective Multicenter Study.

Background: This retrospective multicenter study investigates the impact of obesity on short-term surgical outcomes in patients with heart failure and reduced ejection fraction (HFrEF) undergoing coronary artery bypass grafting (CABG). Given the rising global prevalence of obesity and its known cardiovascular implications, understanding its specific effects in high-risk groups like HFrEF patients is crucial. Methods: The study analyzed data from 574 patients undergoing CABG across four German university hospitals from 2017 to 2023. Patients were stratified into 'normal weight' (n = 163) and 'obese' (n = 158) categories based on BMI (WHO classification). Data on demographics, clinical measurements, health status, cardiac history, intraoperative management, postoperative outcomes, and laboratory insights were collected and analyzed using Chi-square, ANOVA, Kruskal-Wallis, and binary logistic regression. Results: Key findings are a significant higher mortality rate (6.96% vs. 3.68%, p = 0.049) and younger age in obese patients (mean age 65.84 vs. 69.15 years, p = 0.003). Gender distribution showed no significant difference. Clinical assessment scores like EuroScore II and STS Score indicated no differences. Paradoxically, the preoperative left ventricular ejection fraction (LVEF) was higher in the obese group (32.04% vs. 30.34%, p = 0.026). The prevalence of hypertension, COPD, hyperlipidemia, and other comorbidities did not significantly differ. Intraoperatively, obese patients required more packed red blood cells (p = 0.026), indicating a greater need for transfusion. Postoperatively, the obese group experienced longer hospital stays (median 14 vs. 13 days, p = 0.041) and higher ventilation times (median 16 vs. 13 h, p = 0.049). The incidence of acute kidney injury (AKI) (17.72% vs. 9.20%, p = 0.048) and delirium (p = 0.016) was significantly higher, while, for diabetes prevalence, there was an indicating a trend towards significance (p = 0.051) in the obesity group, while other complications like sepsis, and the need for ECLS were similar across groups. Conclusions: The study reveals that obesity significantly worsens short-term outcomes in HFrEF patients undergoing CABG, increasing risks like mortality, kidney insufficiency, and postoperative delirium. These findings highlight the urgent need for personalized care, from surgical planning to postoperative strategies, to improve outcomes for this high-risk group, urging further tailored research.

The role of microRNAs in brain metastasis.

Brain metastasis (BM) is the most common type of brain tumor and frequently foreshadows disease progression and poor overall survival with patients having a median survival of 6 months. 70,000 new cases of BM are diagnosed each year in the United States (US) and the incidence rate for BM is increasing with improved detection. MicroRNAs (miRNAs) are small non-coding RNAs that serve as critical regulators of gene expression and can act as powerful oncogenes and tumor suppressors. MiRNAs have been heavily implicated in cancer and proposed as biomarkers or therapeutic targets or agents. In this review, we summarize an extensive body of scientific work investigating the role of microRNAs in BM. We discuss miRNA dysregulation, functions, targets, and mechanisms of action in BM and present the current standing of miRNAs as biomarkers and potential therapeutics for BM. We conclude with future directions of miRNA basic and clinical research in BM.

Expression of nonmuscle myosin IIC is regulated by non-canonical binding activity of miRNAs.

The expression of mechanoresponsive nonmuscle myosin II (NMII)C is found to be inducible during tumor progression, but its mechanism is yet to be explored. Here, we report a group of microRNAs (mmu-miR-200a-5p, mmu-miR-532-3p, mmu-miR-680, and mmu-miR-1901) can significantly repress the expression of nonmuscle myosin IIC (NMIIC). Interestingly, these microRNAs have both canonical and non-canonical binding sites at 3/UTR and coding sequence (CDS) of NMIIC's heavy chain (HC) mRNA. Each of the miRNA downregulates NMHC-IIC to a different degree as assessed by dual-luciferase and immunoblot analyses. When we abolish the complementary base pairing at canonical binding site, mmu-miR-532-3p can still bind at non-canonical binding site and form Argonaute2 (AGO2)-miRNA complex to downregulate the expression of NMIIC. Modulating the expression of NMIIC by miR-532-3p in mouse mammary tumor cells, 4T1, increases its tumorigenic potential both in vitro and in vivo. Together, these studies provide the functional role of miRNA's non-canonical binding mediated NMIIC regulation in tumor cells.

On- vs. Off-Pump CABG in Heart Failure Patients with Reduced Ejection Fraction (HFrEF): A Multicenter Analysis.

OBJECTIVE: This study aimed to compare postoperative outcomes and 30-day mortality in patients with reduced ejection fraction (<40%) who underwent isolated coronary artery bypass grafting (CABG) with (ONCAB) and without (OPCAB) the use of cardiopulmonary bypass. METHODS: data from four university hospitals in Germany, spanning from January 2017 to December 2021, were retrospectively analyzed. A total of 551 patients were included in the study, and various demographic, intraoperative, and postoperative data were compared. RESULTS: demographic parameters did not exhibit any differences. However, the OPCAB group displayed notably higher rates of preoperative renal insufficiency, urgent surgeries, and elevated EuroScore II and STS score. During surgery, the ONCAB group showed a significantly higher rate of complete revascularization, whereas the OPCAB group required fewer intraoperative transfusions. No disparities were observed in 30-day/in-hospital mortality for the entire cohort and the matched population between the two groups. Subsequent to surgery, the OPCAB group demonstrated significantly shorter mechanical ventilation times, reduced stays in the intensive care unit, and lower occurrences of ECLS therapy, acute kidney injury, delirium, and sepsis. CONCLUSIONS: the study's findings indicate that OPCAB surgery presents a safe and viable alternative, yielding improved postoperative outcomes in this specific patient population compared to ONCAB surgery. Despite comparable 30-day/in-hospital mortality rates, OPCAB patients enjoyed advantages such as decreased mechanical ventilation durations, shorter ICU stays, and reduced incidences of ECLS therapy, acute kidney injury, delirium, and sepsis. These results underscore the potential benefits of employing OPCAB as a treatment approach for patients with coronary heart disease and reduced ejection fraction.

miR-3174 Is a New Tumor Suppressor MicroRNA That Inhibits Several Tumor-Promoting Genes in Glioblastoma.

microRNAs (miRNAs) play an important role in the pathology of glioblastoma (GBM), which is the most malignant and most common primary malignant brain tumor. miRNAs can target multiple genes simultaneously and are considered as potential therapeutic agents or targets. This study aimed to determine the role of miR-3174 in the pathobiology of GBM using both in vitro and in vivo approaches. This is the first study deciphering the role of miR-3174 in GBM. We studied the expression of miR-3174 and found it to be downregulated in a panel of GBM cell lines, GSCs and tissues relative to astrocytes and normal brain tissue. This finding led us to hypothesize that miR-3174 has a tumor-suppressive role in GBM. Exogenous expression of miR-3174 inhibited GBM cell growth and invasion, and hampered the neurosphere formation ability of GSCs. miR-3174 downregulated the expression of multiple tumor-promoting genes including CD44, MDM2, RHOA, PLAU and CDK6. Further, overexpression of miR-3174 reduced tumor volume in nude mice with intracranial xenografts. Immuno-histochemical study of brain sections with intracranial tumor xenografts revealed the pro-apoptotic and anti-proliferative activity of miR-3174. In conclusion, we demonstrated that miR-3174 has a tumor-suppressive role in GBM and could be exploited for therapeutic purposes.

PP2A modulation overcomes multidrug resistance in chronic lymphocytic leukemia via mPTP-dependent apoptosis.

Targeted therapies such as venetoclax (VEN) (Bcl-2 inhibitor) have revolutionized the treatment of chronic lymphocytic leukemia (CLL). We previously reported that persister CLL cells in treated patients overexpress multiple antiapoptotic proteins and display resistance to proapoptotic agents. Here, we demonstrated that multidrug-resistant CLL cells in vivo exhibited apoptosis restriction at a pre-mitochondrial level due to insufficient activation of the Bax and Bak (Bax/Bak) proteins. Co-immunoprecipitation analyses with selective BH domain antagonists revealed that the pleiotropic proapoptotic protein (Bim) was prevented from activating Bax/Bak by "switching" interactions to other upregulated antiapoptotic proteins (Mcl-1, Bcl-xL, Bcl-2). Hence, treatments that bypass Bax/Bak restriction are required to deplete these resistant cells in patients. Protein phosphatase 2A (PP2A) contributes to oncogenesis and treatment resistance. We observed that small-molecule activator of PP2A (SMAP) induced cytotoxicity in multiple cancer cell lines and CLL samples, including multidrug-resistant leukemia and lymphoma cells. The SMAP (DT-061) activated apoptosis in multidrug-resistant CLL cells through induction of mitochondrial permeability transition pores, independent of Bax/Bak. DT-061 inhibited the growth of wild-type and Bax/Bak double-knockout, multidrug-resistant CLL cells in a xenograft mouse model. Collectively, we discovered multidrug-resistant CLL cells in patients and validated a pharmacologically tractable pathway to deplete this reservoir.

Impact of Mitral Regurgitation Etiology on Mitral Surgery After Transcatheter Edge-to-Edge Repair: From the CUTTING-EDGE Registry.

BACKGROUND: Although >150,000 mitral TEER procedures have been performed worldwide, the impact of MR etiology on MV surgery after TEER remains unknown. OBJECTIVES: The authors sought to compare outcomes of mitral valve (MV) surgery after failed transcatheter edge-to-edge repair (TEER) stratified by mitral regurgitation (MR) etiology. METHODS: Data from the CUTTING-EDGE registry were retrospectively analyzed. Surgeries were stratified by MR etiology: primary (PMR) and secondary (SMR). MVARC (Mitral Valve Academic Research Consortium) outcomes at 30 days and 1 year were evaluated. Median follow-up was 9.1 months (IQR: 1.1-25.8 months) after surgery. RESULTS: From July 2009 to July 2020, 330 patients underwent MV surgery after TEER, of which 47% had PMR and 53.0% had SMR. Mean age was 73.8 ± 10.1 years, median STS risk at initial TEER was 4.0% (IQR: 2.2%-7.3%). Compared with PMR, SMR had a higher EuroSCORE, more comorbidities, lower LVEF pre-TEER and presurgery (all P < 0.05). SMR patients had more aborted TEER (25.7% vs 16.3%; P = 0.043), more surgery for mitral stenosis after TEER (19.4% vs 9.0%; P = 0.008), and fewer MV repairs (4.0% vs 11.0%; P = 0.019). Thirty-day mortality was numerically higher in SMR (20.4% vs 12.7%; P = 0.072), with an observed-to-expected ratio of 3.6 (95% CI: 1.9-5.3) overall, 2.6 (95% CI: 1.2-4.0) in PMR, and 4.6 (95% CI: 2.6-6.6) in SMR. SMR had significantly higher 1-year mortality (38.3% vs 23.2%; P = 0.019). On Kaplan-Meier analysis, the actuarial estimates of cumulative survival were significantly lower in SMR at 1 and 3 years. CONCLUSIONS: The risk of MV surgery after TEER is nontrivial, with higher mortality after surgery, especially in SMR patients. These findings provide valuable data for further research to improve these outcomes.

Explant vs Redo-TAVR After Transcatheter Valve Failure: Mid-Term Outcomes From the EXPLANTORREDO-TAVR International Registry.

BACKGROUND: Valve reintervention after transcatheter aortic valve replacement (TAVR) failure has not been studied in detail. OBJECTIVES: The authors sought to determine outcomes of TAVR surgical explantation (TAVR-explant) vs redo-TAVR because they are largely unknown. METHODS: From May 2009 to February 2022, 396 patients in the international EXPLANTORREDO-TAVR registry underwent TAVR-explant (181, 46.4%) or redo-TAVR (215, 54.3%) for transcatheter heart valve (THV) failure during a separate admission from the initial TAVR. Outcomes were reported at 30 days and 1 year. RESULTS: The incidence of reintervention after THV failure was 0.59% with increasing volume during the study period. Median time from index-TAVR to reintervention was shorter in TAVR-explant vs redo-TAVR (17.6 months [IQR: 5.0-40.7 months] vs 45.7 months [IQR: 10.6-75.6 months]; P < 0.001], respectively. TAVR-explant had more prosthesis-patient mismatch (17.1% vs 0.5%; P < 0.001) as the indication for reintervention, whereas redo-TAVR had more structural valve degeneration (63.7% vs 51.9%; P = 0.023), with a similar incidence of ≥moderate paravalvular leak between groups (28.7% vs 32.8% in redo-TAVR; P = 0.44). There was a similar proportion of balloon-expandable THV failures (39.8% TAVR-explant vs 40.5% redo-TAVR; P = 0.92). Median follow-up was 11.3 (IQR: 1.6-27.1 months) after reintervention. Compared with redo-TAVR, TAVR-explant had higher mortality at 30 days (13.6% vs 3.4%; P < 0.001) and 1 year (32.4% vs 15.4%; P = 0.001), with similar stroke rates between groups. On landmark analysis, mortality was similar between groups after 30 days (P = 0.91). CONCLUSIONS: In this first report of the EXPLANTORREDO-TAVR global registry, TAVR-explant had a shorter median time to reintervention, with less structural valve degeneration, more prosthesis-patient mismatch, and similar paravalvular leak rates compared with redo-TAVR. TAVR-explant had higher mortality at 30 days and 1 year, but similar rates on landmark analysis after 30 days.

Fob1-dependent condensin recruitment and loop extrusion on yeast chromosome III.

Despite recent advances in single-molecule and structural analysis of condensin activity in vitro, mechanisms of functional condensin loading and loop extrusion that lead to specific chromosomal organization remain unclear. In Saccharomyces cerevisiae, the most prominent condensin loading site is the rDNA locus on chromosome XII, but its repetitiveness deters rigorous analysis of individual genes. An equally prominent non-rDNA condensin site is located on chromosome III (chrIII). It lies in the promoter of a putative non-coding RNA gene called RDT1, which is in a segment of the recombination enhancer (RE) that dictates MATa-specific chrIII organization. Here, we unexpectedly find that condensin is recruited to the RDT1 promoter in MATa cells through hierarchical interactions with Fob1, Tof2, and cohibin (Lrs4/Csm1), a set of nucleolar factors that also recruit condensin to the rDNA. Fob1 directly binds to this locus in vitro, while its binding in vivo depends on an adjacent Mcm1/α2 binding site that provides MATa cell specificity. We also uncover evidence for condensin-driven loop extrusion anchored by Fob1 and cohibin at RDT1 that unidirectionally extends toward MATa on the right arm of chrIII, supporting donor preference during mating-type switching. S. cerevisiae chrIII therefore provides a new platform for the study of programmed condensin-mediated chromosome conformation.

Indocyanine green clearance predicts outcome in patients undergoing transcatheter valve intervention for severe atrio-ventricular valve regurgitation.

OBJECTIVES: Severe mitral regurgitation (MR) and tricuspid regurgitation (TR) aggravate haemodynamic stress leading to congestive heart failure with impaired hepatic function, also known as cardiohepatic syndrome (CHS). Current perioperative risk calculators do not sufficiently consider CHS and serum liver function parameters lack sensitivity to diagnose CHS. Indocyanine green and its elimination (measured by the LIMON® test) represent a dynamic and non-invasive test which correlates with the hepatic function. Nevertheless, its utility in the setting of transcatheter valve repair/replacement (TVR) to predict CHS and outcome remains unknown. METHODS: We analysed liver function and outcomes of patients undergoing TVR for MR or TR between August 2020 and May 2021 at the Munich University Hospital. RESULTS: Out of a total of 44 patients treated at the University Hospital of Munich, 21 (48%) were treated for severe MR, 20 (46%) for severe TR and 3 (7%) for both diseases. Procedural success defined as MR/TR ≤2+ was 94% among MR patients and 92% among TR patients. While classical serum liver function parameters did not change after TVR, there was a significant improvement in liver function as assessed by the LIMON® test (P ≤ 0.001). Patients with baseline indocyanine green plasma disappearance rate <12.95%/min showed significantly increased 1-year mortality (hazard ratio: 1.54, 95% confidence interval: 1.05-2.25, P = 0.027) and lower New York Hear Association class improvement (P = 0.05). CONCLUSIONS: Especially in the context of the recently stressed importance of a careful patient selection prior to the interdisciplinary treatment of valvular heart disease, the LIMON® test may provide further real-time information on the patients' cardiohepatic injury and prognosis.

Virulence of Staphylococcus Infection in Surgically Treated Patients With Endocarditis : A Multicenter Analysis.

OBJECTIVE: Infective endocarditis (IE) caused by Staphylococcus species (spp.) is believed to be associated with higher morbidity and mortality rates. We hypothesize that Staphylococcus spp. are more virulent compared with other commonly causative bacteria of IE with regard to short-term and long-term mortality. BACKGROUND: It remains unclear if patients suffering from IE due to Staphylococcus spp. should be referred for surgical treatment earlier than other IE patients to avoid septic embolism and to optimize perioperative outcomes. MATERIALS AND METHODS: The database of the CAMPAIGN registry, comprising 4917 consecutive patients undergoing heart valve surgery, was retrospectively analyzed. Patients were divided into 2 groups with regard to the identified microorganisms: Staphylococcus group and the non- Staphylococcus group. The non- Staphylococcus group was subdivided for further analyses: Streptococcus group, Enterococcus group, and all other bacteria groups. RESULTS: The respective mortality rates at 30 days (18.7% vs 11.8%; P <0.001), 1 year (24.7% vs 17.7%; P <0.001), and 5 years (32.2% vs 24.5%; P <0.001) were significantly higher in Staphylococcus patients (n=1260) compared with the non- Staphylococcus group (n=1787). Multivariate regression identified left ventricular ejection fraction <30% ( P <0.001), chronic obstructive pulmonary disease ( P =0.045), renal insufficiency ( P =0.002), Staphylococcus spp. ( P =0.032), and Streptococcus spp. ( P =0.013) as independent risk factors for 30-day mortality. Independent risk factors for 1-year mortality were identified as: age ( P <0.001), female sex ( P =0.018), diabetes ( P =0.018), preoperative stroke ( P =0.039), chronic obstructive pulmonary disease ( P =0.001), preoperative dialysis ( P <0.001), and valve vegetations ( P =0.004). CONCLUSIONS: Staphylococcus endocarditis is associated with an almost twice as high 30-day mortality and significantly inferior long-term outcome compared with IE by other commonly causative bacteria. Patients with Staphylococcus infection are more often female and critically ill, with >50% of these patients suffering from clinically relevant septic embolism. Early diagnosis and referral to a specialized center for surgical treatment are strongly recommended to reduce the incidence of preoperative deterioration and stroke due to septic embolism.