Open Heart Surgery Research Articles

A qualitative study exploring the experiences and needs of fear of disease progression in patients after open-heart surgery.

Open-heart surgery (OHS) is a stressful event for patients, all of whom experience varying levels of worry and fear, leading to fear of disease progression (FoP). An in-depth understanding of the experiences and needs of FoP in patients after OHS is beneficial for healthcare providers to make optimal decisions, but this has not been reported. We aimed to explore the experiences and needs of FoP in patients after OHS by adopting a qualitative interview method. A qualitative study was performed to recruit 18 qualified patients through purposive sampling and then conduct face-to-face, semi-structured interviews. The research setting was the cardiovascular surgery ward of a tertiary hospital in Guangdong, China, in 2024. The data were analyzed and extracted using conventional content analysis. In the study, four themes emerged: a) sources of FoP; b) effects of FoP; c) attitudes towards FoP; d) supportive service needs. The desire to obtain meaningful assistance and the profound experiences of FoP in patients after OHS gave rise to these themes. FoP following OHS is a subjective feeling characterized by fear and discomfort. Care workers must completely grasp the patients' fear and provide personalized interventions to support them through the difficult recovery phase, which will also be the focus of future efforts in this area.

Abstract 4120469: Racial and ethnic disparities in catheter based interventions vs. open heart surgery in congenital heart disease

Introduction: Transcatheter cardiac interventions have emerged as a viable alternative to open heart surgery for specific congenital heart disease lesions. There is literature to support racial and ethnic disparities in medicine, indicating that patients from racially and ethnically marginalized populations are less likely to receive advanced less invasive procedures. This study seeks to delve into the existence of such inequities between transcatheter and surgical interventions, shedding light on potential inequalities in access and outcomes. Methods: We analyzed California and Florida's State Inpatient and Ambulatory Surgery Databases from 2005 to 2017 to study patients under 18 admitted with diagnosis of atrial septal defect, pulmonary stenosis, aortic stenosis, and ventricular septal defects. Multivariable logistic regression, adjusted for patient characteristics, assessed race and ethnicity's influence on procedure type and in-hospital mortality. We also used log-transformed linear regression to examine associations with length of stay, hospitalization cost, and cost per day. Results: We identified 13,771 records who had open surgeries, and 2,045 records who had CBI. Compared to non-Hispanic White patients, Black patients were significantly more likely to undergo open surgical procedures (adjusted Odds Ratio [aOR] 1.49, p < .001). Additionally, Black, Hispanic, and other race patients had higher risks of in-hospital death (aOR 1.92, p = 0.016 for Black; aOR 1.93, p < 0.01 for Hispanic; aOR 2.37, p < 0.01 for other races). Black and Hispanic patients also experienced longer lengths of stay (Adjusted Means Ratio [aMR] 1.34, p < 0.01 for Black; aMR 1.16, p < 0.01 for Hispanic), and higher costs (aMR 1.12, p = .01 for Black; aMR 1.11, p = .01 for Hispanic), but Black patients had a lower cost per day (aMR 0.96, p = .02). Conclusion: Racial and ethnic gaps persist in pediatric cardiac care, with Black patients facing reduced access to less invasive procedures, higher mortality rates, longer hospital stays, and increased costs compared to non-Hispanic whites. However, the higher costs are likely attributed to longer hospital stays rather than expensive interventions. It is imperative to tackle these disparities to prioritize patient-centered care and streamline resource allocation in healthcare.

Robotic Versus Thoracoscopic Minimally Invasive Mitral Valve Surgery: A Systematic Review and Meta-Analysis of Matched Studies.

Mitral regurgitation is the most prevalent form of valvular heart disease, impacting over 24 million people globally. Robotic and thoracoscopic minimally invasive mitral valve repair (MIMR) techniques have emerged as viable alternatives to traditional open-heart surgery. However, the comparative effectiveness and safety of these 2 approaches remain underexplored. This systematic review and meta-analysis, conducted according to Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, aimed to compare robotic and thoracoscopic MIMR outcomes. A literature search was performed across PubMed, Scopus, and Embase databases to identify studies comparing these 2 surgical techniques. Eligible studies included randomized controlled trials and cohort studies. Six propensity score-matched studies and 1 retrospective cohort study, involving 11,823 patients, were included, with 5851 undergoing robotic mitral valve repair and 5972 receiving thoracoscopic MIMR. No significant differences were found in perioperative mortality [risk ratio (RR): 0.97, 95% confidence interval (CI): 0.65-1.45] or pump/clamp times. Robotic surgery was associated with longer operative times (mean difference: 33.01 minutes) and higher intraoperative transfusion rates (RR: 1.53, 95% CI: 1.07-2.18), but a lower risk of atrial fibrillation (RR: 0.89, 95% CI: 0.83-0.95). In conclusion, robotic and thoracoscopic MIMR show comparable mortality and overall safety profiles. However, robotic surgery may require longer operative times and increased transfusion needs, while reducing the risk of atrial fibrillation. Further high-quality, randomized studies are warranted to validate these findings.

The impact of NICU client-centered, written, and visual reporting on maternal stress and attachment post-infant heart surgery

BackgroundIn this study, we explored the impact of client-centered, written and visual reporting based on the Newborn Individualized Care and Assessment Program (NIDCAP) approach on stress levels and attachment among mothers with neonates hospitalized in Neonatal Intensive Care Unit following open heart surgery. MethodsThe clinical trial involved 70 mothers with an infant in the neonatal intensive care unit following heart surgery at Children's Medical Center in Tehran. Eligible participants were randomly assigned to either the control group (35 mothers) or the intervention group (35 mothers). While the control group adhered to regular daily visits to their sick infant as part of the hospital routine, the intervention group in addition to these visits, received daily written and visual reports, based on the NIDCAP approach standards for a week through WhatsApp messenger. Maternal Stress levels and attachment were assessed on the 7th day and again two weeks post-intervention. Data analysis was conducted using SPSS software. ResultsThe intervention group experienced a significant reduction in stress levels. Mean stress levels decreased from 102.57 ± 30.8 to 72.25 ± 15.81 on the day 7th. Two weeks post-intervention, the average stress level further decreased to 62.08 ± 15.00(p < 0.05). Interestingly there was a slight increase in attachment score in the intervention group after one week. However, at the end of the study, there was no significant difference between the intervention and control groups. ConclusionClient-centered reporting based on the NIDCAP approach could substantially reduce stress levels among mothers with hospitalized newborns in neonatal cardiac surgery units. Especially when the constant presence of parents at the newborn's bedside is not possible, this approach could be considered a practical, innovative, and effective method to reduce maternal stress levels in the NICUs after heart surgery.

Predicting mortality of elderly patients undergoing open heart surgery with delirium using sequential organ failure assessment (SOFA), multi-organ dysfunction (MODS), and logistic organ dysfunction system (LODS) scores

PurposeThis study aims to assess the predictive accuracy of SOFA, MODS, and LODS scores in determining the mortality of elderly undergoing open heart surgery with delirium. MethodsA prospective study involved 111 elderly patients who met the inclusion criteria. Data were collected using scoring systems: SOFA, MODS, and LODS. ResultsUpon final follow-up, 86.5 % of the patients had recovered, 13.5 % had died. Sensitivity, specificity, negative, and positive predictive values for predicting mortality in elderly patients were calculated for the SOFA score as 99 %, 73 %, 98 %, and 76 %, respectively. For the MODS score, these values were 95 %, 60 %, 95 %, and 67 %; for the LODS score, they were 92 %, 73 %, 92 %, and 75 %, respectively. The overall accuracy of the three scores—SOFA, MODS, and LODS—was 84 %, 76 %, and 82 %, respectively. ConclusionThe results indicated that the SOFA score exhibited the highest sensitivity and specificity in predicting mortality among elderly individuals

031. Urine Neutrophil Gelatinase-Associated Lipocalin (NGAL) Levels as a Predictor of Early Acute Kidney Injury in Post Coronary Artery Bypass Graft (CABG) Patients in H. Adam Malik Hospital Medan

Background: One of the main complications after open heart surgery is acute kidney injury. Coronary Artery Bypass Graft surgery is one of the main factors in this complication. Currently, the use of serum creatinine as one of the diagnostic criteria for AKI is not sensitive for diagnosing AKI at an early stage. Elevated urine NGAL levels are more indicative of a renal damage process than an increase in circulation. An increase in NGAL levels in urine can occur 100 times faster than circulating NGAL. Thus our research aimed to view NGAL ability to predict AKI in CABG patient. Methods: This research is an observational study with cross-sectional data collection methods to find out whether NGAL can be a predictor of AKI in patients who have undergone CABG surgery. Results: The collection of research subjects was stopped when the number of samples had been reached so that this study was a cohort study with consecutive sampling techniques. In the results of this study, we obtained 31 research samples. In 31 research samples, it was found that the average age was 61.46 years with a standard deviation of 8.2 years. This study was dominated by male gender with a total of 20 people or 64% of the total sample. After CABG surgery, it was found that 4 patients had postoperative acute renal failure or 13.3% of the total sample. The sensitivity of the instrument is 100% with a specificity of 96%. The accuracy of the NGAL is 97.5%. Conclusion: NGAL is a useful parameter to predict AKI and would have significant advantage however further study with multi-center design would be necessary to validate these result.

Myocardial inflammation is associated with impaired mitochondrial oxidative capacity in ischaemic cardiomyopathy.

Myocardial inflammation and impaired mitochondrial oxidative capacity are hallmarks of heart failure (HF) pathophysiology. The extent of myocardial inflammation in patients suffering from ischaemic cardiomyopathy (ICM) or dilated cardiomyopathy (DCM) and its association with mitochondrial energy metabolism are unknown. We aimed at establishing a relevant role of cardiac inflammation in the impairment of mitochondrial energy production in advanced ischaemic and non-ischaemic HF. We included 81 patients with stage D HF (ICM, n=44; DCM, n=37) undergoing left ventricular assist device implantation (n=59) or heart transplantation (n=22) and obtained left ventricular tissue samples during open heart surgery. We quantified mitochondrial oxidative capacity, citrate synthase activity (CSA) and fibrosis and lymphocytic infiltration. We considered infiltration of >14 CD3+ cells/mm2 relevant inflammation. Patients with ICM or DCM did not differ regarding age (61.5±5.7 vs. 56.5±12.7years, P=0.164), sex (86% vs. 84% male, P=0.725), type 2 diabetes mellitus (34% vs. 18%, P=0.126) or chronic kidney disease (8% vs. 11%, P=0.994). ICM exhibited oxidative capacity reduced by 23% compared to DCM (108.6±41.4 vs. 141.9±59.9pmol/(s*mg), P=0.006). Maximum production of reactive oxygen species was not significantly different between ICM and DCM (0.59±0.28 vs. 0.69±0.36pmol/(s*ml), P=0.196). Mitochondrial content, detected by CSA, was lower in ICM (359.6±164.1 vs. 503.0±198.5nmol/min/mg protein, P=0.002). Notably, relevant inflammation was more common in ICM (27% vs. 6%, P=0.024), and the absolute number of infiltrating leucocytes correlated with lower oxidative capacity (r=-0.296, P=0.019). Fibrosis was more prevalent in ICM (20.9±21.2 vs. 7.2±5.6% of area, P=0.002), but not associated with oxidative capacity (r=-0.13, P=0.327). More than every fourth ICM patient with advanced HF displays myocardial inflammation in the range of inflammatory cardiomyopathy associated with reduced mitochondrial oxidative capacity. Future studies may evaluate inflammation in ICM at earlier stages in standardised fashion to explore the therapeutic potential of immunosuppression to influence trajectories of HF in ICM.

Nociception level index-directed superficial parasternal intercostal plane block vs erector spinae plane block in open-heart surgery: a propensity matched non-inferiority clinical trial.

This single-center study explored the efficacy of superficial parasternal intercostal plane block (SPIPB) versus erector spinae plane block (ESPB) in opioid-sparing within Nociception Level (NOL) index-directed anesthesia for elective open-heart surgery. After targeted propensity matching, 19 adult patients given general anesthesia with preincisional SPIPB were compared to 33 with preincisional ESPB. We hypothesized that SPIPB is non-inferior to ESPB in reducing total intraoperative fentanyl consumption, with a non-inferiority margin (δ) set at 0.1mg. Intraoperative fentanyl dosing targeted a NOL index ≤ 25. Postoperatively, paracetamol 1g 6-hourly and morphine for numeric rating scale (NRS) ≥ 4 were administered. This study could not demonstrate that SPIPB was inferior to ESPB for total intraoperative fentanyl consumption, as the confidence interval for the median difference of 0.1mg (95% CI 0.05-0.15) crossed the predefined δ, with the lower bound falling below and the upper bound exceeding δ, p = 0.558. SPIPB led to higher postoperative morphine use at 24 and 48h: 0 (0-40.6) vs. 59.5 (28.5-96.1) µg kg-1, p < 0.001 and 22.2 (0-42.6) vs. 63.5 (28.5-96.1) µg kg-1, p = 0.001. Four times fewer SPIPB patients remained morphine-free at 48h, p < 0.001, and their time to first morphine dose was three times shorter compared to ESPB patients, p = 0.001. SPIPB led to higher time-weighted average NRS scores at rest, 1 (0-1) vs. 1 (1-2), p = 0.004, and with movement, 2 (1-2) vs. 3 (2-3), p = 0.002, calculated over the 48-h period post-extubation. The SPIPB group had a significantly higher average NOL index, p = 0.003, and greater NOL index variability, p = 0.027. This study could not demonstrate that SPIPB was inferior to ESPB for intraoperative fentanyl consumption. Significant differences were observed in secondary outcomes, with SPIPB leading to higher postoperative morphine use, higher pain scores, and reduced nociception control.

Insights into type 2 diabetes mellitus in atrial fibrillation patients: a proteomics approach

Abstract Introduction Atrial fibrillation (AF) and Type 2 Diabetes Mellitus (T2DM) are two closely interconnected conditions, sharing a complex relationship within cardiac pathophysiology. Common risk factors such as obesity, hypertension, inflammation, and endothelial dysfunction contribute to their coexistence. T2DM is known to drive cardiac fibrosis and promote electrical and structural remodeling of the heart, creating a substrate conducive to AF onset, while AF in T2DM patients increases the risk of adverse cardiovascular outcomes, such as stroke. Understanding this complex relationship is pivotal for improving the therapeutic and preventive strategies for these patients. This study aims to examine the proteomic differences between AF patients with and without T2DM, providing novel insights into pathophysiological mechanisms and identifying novel therapeutic targets and biomarkers. Methods In total, 14 AF patients undergoing open-heart surgery, comprising of 6 T2DM individuals and 8 non-T2DM individuals have been included. The mean age of the T2DM patients was 69.5 ± 10 years, while the non-T2DM was 69.3 ± 8.2 and BMI was 29.2 ± 2.9 and 29.5 ± 3 respectively. Right atrial appendages (RAA) from these patients were obtained in an RNA stabilization solution during open-heart surgery and processed using the phenol-based method for protein extraction. The proteins were digested with trypsin to generate peptides, followed by an additional clean-up step using C18 pipette tips. The prepared peptide samples were analyzed by employing a label-free-based quantitative (LFQ) approach, using a C18 (75cmx75cm) column. Proteomic analysis was performed using a Nano liquid chromatography system coupled to tandem mass spectrometer (nano LC-MS/MS), followed by a comprehensive bioinformatics analysis, using appropriate software. Results A total of 1548 proteins were identified, of which 899 could be quantified using LFQ analysis. Applying strict significance criteria, including FDR &amp;lt;0.1 and Abundance ratio (AR)&amp;gt;2 or &amp;lt;0.5, we identified 100 differential expressed proteins, with 21 upregulated and 79 downregulated in T2DM (Fig.1). Most notably, DPP9 and ATP1A2 were overexpressed in hearts of AF patients with T2DM (AR=100), while INPPL1 and ARID5A were underexpressed (AR=0.01), thereby representing attractive therapeutic targets. In pathway enrichment analysis (Fig.2), the dysregulated proteins participate in noteworthy pathways, including Non-alcoholic fatty liver disease (NAFLD), Type II diabetes mellitus, and Insulin signaling pathway. Conclusion Given the increased morbidity associated with the coexistence of AF and T2DM, there is a pressing need for novel therapeutic strategies tailored to this patient population. While AF and T2DM share certain molecular characteristics in the heart, this study emphasizes the necessity for further evaluation and validation of the distinct proteomic signatures identified.Fig.1:Volcano PlotFig.2:Protein Enrichment Network

Impact of atrial fibrillation on mortality and non-fatal clinical outcomes in 28 492 patients who had undergone open-heart aortic versus mitral valve surgery: a statewide population-linkage study

Abstract Background Postoperative atrial fibrillation (AF) is common after cardiac surgery and has been associated with increased mortality and morbidity. Few studies have defined the impact of AF status (New-AF versus Prior-AF) on clinical outcomes during long-term follow-up and compared AF-related clinical outcomes between patients who had undergone isolated aortic valve surgery (AVSx) or mitral valve surgery (MVSx). Purpose This study aims to examine the impact of AF status on clinical outcomes in patients who had undergone AVSx versus MVSx using a statewide-population administrative database. Methods Patients who had open-heart cardiac valve surgery (1 January 2003 to 31 March 2021) identified from the Admitted-Patient-Data-Collection database in an Australian state, were stratified by AF status (No-AF vs New-AF vs Prior-AF during index admission for valve surgery) and followed up to 31 March 2022. A linkage look-back to year-2001 was performed to identify prior-AF history. Kaplan-Meier and multivariable Cox regression were performed to assess the impact of AF status on all-cause mortality. Fine-Gray competing risk analysis to account for the competing death events was used to assess non-fatal clinical outcomes. Results The overall cohort comprised 28 492 patients (median age 71.6yrs [interquartile range (IQR) 62.7–78.3yrs; 65.6% males): AVSx, n=18949; MVSx, n=9543 (Table 1). During a median follow-up of 6.6yrs (3.42–10.5yrs), Prior-AF and New-AF patients had significantly higher all-cause mortality (AVSx – Prior-AF: 1771 (57.9%) vs New-AF: 2854 (41.5%) vs No-AF: 2961 (32.8%); MVSx – Prior-AF: 1126 (41.0%) vs New-AF: 1034 (29.8%) vs No-AF: 747 (22.4%) (both Kaplan-Meier logrank P&amp;lt;0.001). After adjusting for differences in baseline characteristics and admission year-groups, in the AVSx subgroup, both new-AF and prior-AF were independently associated with all-cause mortality (aHR=1.16, 95%CI=1.10–1.22; aHR=1.69, 95%CI=1.59–1.79 respectively, both P&amp;lt;0.001) compared to no-AF patients. In the MVSx subgroup, only prior-AF was associated with increased risk of all-cause mortality (aHR=1.47, 95% CI=1.33–1.61, P&amp;lt;0.001). Competing risk analyses showed higher rehospitalisation rates for AF and congestive cardiac failure for new-AF and prior-AF groups compared to No-AF patients after both AVSx and MVSx, whereas the rehospitalisation rate for ischemic stroke was only significantly higher in the AVSx new-AF and prior-AF subgroups (all p &amp;lt; 0.05) (Table 2). Conclusions Patients undergoing open-heart aortic or mitral valve surgery are at risk of significant adverse clinical outcomes including death, heart failure and ischaemic stroke, with the target valve and baseline AF status having a differential impact on clinical outcomes. Drivers behind these high rates of adverse outcomes should be explored further and strategies should be developed and tailored accordingly to different surgical patient groups to improve their prognosis.

Novel role of human epicardial adipocyte-derived SPARCL1 in suppression of postoperative atrial fibrillation in patients undergoing cardiovascular surgery

Abstract Background Postoperative atrial fibrillation (POAF) occurs in 20-50% after cardiovascular surgery and is associated with the short and long-term morbidity/mortality. The epicardial adipose tissue (EAT) may have a potential role to regulate the incidence of POAF. Purpose We explored the possible role of human epicardial adipocyte-derived adipokines in the regulation of the myocardial redox state and POAF. Methods We prospectively evaluated 149 patients without known AF who underwent scheduled open-heart cardiovascular surgery between May 2020 and November 2022. They were divided into POAF or Non-POAF group and followed up after discharge (476.6 ± 290.0 days). POAF was defined as AF lasting more than 30 seconds after the surgery. Human EAT samples were obtained from these patients during surgery and the preadipocytes were isolated. Preadipocytes were terminally differentiated to mature adipocytes and mRNAs were extracted. Genome-wide expression profiling of 6 vs. 6 matched samples of the POAF and Non-POAF groups was performed using Microarray analysis, and the results were validated with qPCR in all the cohort samples. The effects of secreted adipokines on the cardiomyocytes were assessed in terms of oxidative stress. Superoxide and whole reactive oxygen species (ROS) were evaluated with luminometry and live-cell fluorescent probes respectively. As the oxidative stress associated signalling, the phosphorylation of ERK and p38-MAPK were evaluated with western blotting. Angiotensin II (Ang-II) was used to induce oxidative stress and phosphorylation of MAPK. Results POAF was observed in 53 patients (36%). Microarray analysis (n = 6) revealed that there were 132 down- or up-regulated cording genes in epicardial adipocytes of the POAF group compared to the Non-POAF group. Of these genes, 11 genes cording secretable molecules were validated by qPCR (n = 69), showing that only SPARCL1 had significantly downregulated in the POAF group compared to the Non-POAF group (P = 0.005). Superoxide and ROS were induced by Ang II (P &amp;lt; 0.01) and attenuated by SPARCL1 dose-dependent manner (P &amp;lt; 0.01) in neonatal rat cardiomyocytes. The phosphorylation of ERK and p38-MAPK were induced by Ang II (P &amp;lt; 0.01) and attenuated by SPARCL1 (P &amp;lt; 0.01) dose-dependently. Co-culture of human induced pluripotent stem cell-derived atrial cardiomyocytes (iPS-ACM) and human epicardial adipocytes revealed that the adipocytes derived from Non-POAF group suppressed the superoxide (P = 0.002) and ROS (P = 0.02) in iPS-ACM compared to POAF group. Kaplan-Meier survival analysis revealed that the POAF group (P = 0.01) and low SPARCL1 expression in epicardial adipocytes (P = 0.018) were associated with a higher incidence of long-term adverse cardiovascular events after surgery. Conclusion: SPARCL1 derived from epicardial adipocytes may play an important role in the suppression of POAF and long-term cardiovascular events via improving the myocardial redox state.

Histopathology and prognosis of new-onset atrio-ventricular block after coronary artery bypass graft surgery

Abstract Background Atrio-ventricular block (AVB) can often be seen in patients undergoing cardiac procedures. Nevertheless, little is known about the histopathological features of new-onset postoperative AVB prior to the clinical manifestation and its prognostic impact. Purpose This study explores the association of first-degree AVB in ECG and postoperative outcome of patients with either preoperative or a new-onset AVB. Furthermore, histopathological features were analyzed to distinguish the characteristics between preoperative and postoperative AVBs compared to no AVB. Methods CAREBANK is a prospective study with atrial biopsies obtained at the time of open-heart cardiac surgery and long-term follow-up focusing on the adverse events. We analyzed preoperative as well as postoperative ECGs derived after index hospitalization (1-18mo) in patients undergoing CABG. The definition of first-degree AVB was PR-interval ≥200ms. The main outcome of interest was follow-up mortality. Histopathological analysis was used to assess the amount of fibrosis, cardiomyocytes, number of nuclei and macrophages. Results Median follow up time was 4.0 (IQR 2.7 – 5.0) years. First-degree AVB was found in 84/373 (22.5%) preoperative ECGs. Altogether 25/289 (8.7%) cases where ECG was available (after excluding preop AVB, atrial fibrillation) developed first-degree AVB after index hospitalization. New-onset first-degree AVB was associated with increased mortality (aHR 4.033 (95-CI% 1.019–15.965, p=0.047). In atrial histopathological analysis, area covered by cardiomyocytes (p=0.033) as well as area covered by nuclei (p=0.047) were smaller in those with new-onset AVB after surgery, but not in those with preoperative first-degree AVB (p=0.692 and p=0.384) as compared with controls, respectively. Similarly, the total area of fibrosis was greater in those with preoperative first-degree AVB (p&amp;lt;0.001), but not in those with postoperative new-onset AVB (p=0.244). When compared with controls, share of CD68 positive macrophages was similar (p=0.073), but anti-inflammatory CD206 positive M2 macrophages were absent in patients with new-onset AVB (p=0.042). Conclusion Patients with new-onset AVB after CABG have increased mortality in the long-term compared to those without. Histopathology identifies marked differences in macrophage populations between those with and without new-onset AVB.

A sex-specific comparison of valve-in-valve transcatheter aortic valve implantation

Abstract Introduction Valve-in-valve (ViV) transcatheter aortic valve implantation (TAVI) is a viable and less-invasive alternative to open heart surgery in selected patients with bioprosthetic valve dysfunction. Since patients receiving initially a new bioprosthetic aortic valve are predominantly male, data on a sex-specific comparison of ViV-TAVI is scarce. Thus, we compared patient characteristics, procedural outcomes, and 1-year outcomes of female (F) versus male (M) patients with failing bioprosthetic aortic valves undergoing ViV-TAVI. Methods A total of 375 Patients at 3 German centres were included in this analysis. The 1-year mortality was the primary outcome measure, secondary outcomes included VARC-3 defined technical and device success and early safety. Results Overall, 160 (42.6 %) women and 215 (57.4 %) men were included. Women were older (F 81 (77; 84), p &amp;lt; 0.001), had a greater surgical risk (STS PROM F: 9.1 (6.1; 13,9) %, p &amp;lt; 0.001) and a higher rate of previous coronary bypass surgery (F: 25.6 % vs M: 40 %, p = 0.004), while presenting mostly failed valve sizes &amp;lt; 20 mm (F: 59.4 % vs M: 33.4 %, p &amp;lt; 0.001) and therefore higher gradients (F: 40 (31; 50) mmHg vs M: 32 (25; 42) mmHg, p &amp;lt; 0.001). Aortic regurgitation was the mode of failure in 7.5 % of F vs. 14.4 % of M. The number of stentless valves was higher in men (F: 8,1 % vs M: 14 %, p = 0.08). Patients received a self-expanding TAVI prostheses in 79.4 % and 75.8 % respectively in F and M patients. The rates of technical success (F: 75.6 % vs M: 83.3 %, p =0.06), device success (F: 52.5 % vs M: 58.2 %, p = 0.27) and early safety (F: 67.5 % vs M: 67 %, p = 0.91) were comparable between genders. Residual mean gradients were higher in F (F: 15 (11;22) mmHg vs M: 15 (10; 20) mmHg, p = 0.03), while the rates of residual regurgitations were greater in M patients (F: 1 (0.6 %) vs M: 11 (5.1 %), p = 0.04). The Kaplan-Meier estimated 30-day mortality rate (F: 2.5% vs M: 3.3%, p = 0.66) and 1-year mortality rates (F: 10 % vs M: 92.6 %, p = 0.37) were comparable between genders. Conclusion: F and M patients treated by ViV-TAVI have comparable short-term outcomes according to VARC-3-defined endpoints and similar mortality rates after 30 days and 1 year. The residual gradients in F and residual regurgitations in M could be explained by structural features of their failed valves. Further large scale studies are needed to determine, if such procedural outcomes are truly sex-specific.

Trends in Patient Characteristics and Cardiothoracic Surgeries over 14 Years (2010-2023): A Single Center Experience.

Background: as transcatheter technologies have advanced, the patient population that is referred to open heart surgeries has shifted. This study's objective was to evaluate recent trends in the characteristics of patients undergo surgical valvular interventions and coronary revascularizations (CABG) in our center over a period of 14 years. Methods: this is a retrospective analysis of ecological trends in the age, sex, and risk profile (Charlson comorbidity index-CCI) of patients who, from January 2010 to December 2023, underwent CABG, aortic valve replacement (AVR), or mitral valve repair or replacement (with or without tricuspid valve intervention). The data were extracted from electronic clinical files using MD-Clone software. Results: for the CABG procedures, the respective data for 2010 and 2023 were: mean ages 68.0 and 64.6 years; 79.7% and 83.1% males; and mean CCI scores 3.16 and 2.51. The p-values for the cumulative differences over the study period were 0.001, 0.005, and 0.013, respectively. The respective data for isolated AVR were mean ages of 69.2 and 62.9 years; 64.1% and 59.1% males; mean CCI 3.64 and 2.32; p-values: <0.001, 0.229, and 0.019. The respective data for mitral valve procedures were mean ages of 63.6 and 59.8 years, 71.4% and 65.5% males; mean CCI 2.90 and 1.79; p-values: 0.84, 0.422, and 0.318. Conclusions: over a 14-year period, changes were evident in the age, sex distribution, and CCI for operations performed in our center. These changes most likely resulted from accumulated data regarding the advantages and detriments of treatment strategies, mostly of CABG vs. percutaneous coronary intervention; major advancements in transcatheter technologies, mostly in transcatheter AVR; and clinical guidelines facilitating a more collaborative decision-making, open-minded, and personalized approach.

Semaglutide modulates pro-inflammatory neutrophil phenotype induced by supraphysiological levels of the adipokine FABP4 in patients with cardiovascular disease

Abstract Background Increased adiposity is a risk factor for cardiovascular disease (CVD). Adipose tissue is an endocrine organ that releases proteins with pro-inflammatory effects. One of them is FABP4, which levels are increased after adipogenesis. Insulin resistance is linked to supraphysiological levels of this biomarker. Therapies to reduce body weight and improve insulin response, such as the GLP-1 receptor agonists, like semaglutide, have been shown to benefit patients with CVD and obesity, who have a high pro-inflammatory neutrophil profile. Purpose To study the FABP4 effects on neutrophils from patients with cardiovascular disease and cellular models and its possible modulation by semaglutide. Methods We included 11 patients undergoing open heart surgery. Neutrophils from blood were isolated by single-step centrifugation, counted, and same number were treated with FABP4 (100 ng/mL), semaglutide (1nM) or both. Finally, their phenotype was assessed using flow cytometry (FACS). The same treatment conditions were used on differentiated HL-60 cells (dHL-60) to test their phenotype and functionality based on a) oxidative burst capacity using dihydrorhodamine 123 and b) adhesion to coronary artery endothelial cells. At the end, neutrophils phenotype was tested on patients with obesity and diabetes under semaglutide treatment for 6 months, according to clinical practice. Neutrophils phenotype was determined by FACS and FABP4/C5a plasma levels by immunofluorescence assay. Results FABP4 reduced neutrophils’ CD88 (p=0.006) and CXCR2 (p=0.02) levels. This was also verified in dHL60 cells (p=0.01). In these cells, we were also able to observe a CD11b increment after FABP4 treatment (p=0.04), modulated by semaglutide (p=0.02). This phenotype increased the neutrophil-coronary adhesion (p=0.03). Their oxidative burst capacity was attenuated after semaglutide treatment. In addition, 32% of patients underwent semaglutide treatment reduced plasmatic FABP4 (p=0.03) levels and increased CD88 (p=0.01). We confirmed that CD88 modulation does not lead to a change in plasma C5a. Conclusions High FABP4 levels reduce CD88 of neutrophils from patients with cardiovascular disease and enhance their adhesion to coronary endothelial cells. Modulation of the FABP4 effects by semaglutide treatment might suggest a protective mechanism against adiposity/coronary endothelial inflammation.

Epicardial carbohydrate antigen 125 (CA-125) levels, associated with neutrophils activity in heart failure: No differences regarding sex

Abstract Background Carbohydrate antigen 125 (CA125), is the name of the soluble part of mucin-16, after being cleaved, which is detected and increased into circulation in congestive heart failure (HF) patients. Purpose We aimed to study plasma and epicardial fat markers related to inflammation, fibrosis, adiposity, and its association with plasma and epicardial CA125 for understanding the underlying mechanisms of heart failure and the differences between men and women. Methods We have included women and men undergoing open heart surgery (n=134). Epicardial fat biopsy and blood were obtained before the procedure under signed consent. Immunohistochemistry, ELISA, multiplex-Luminex, and real-time PCR were used for analyzing protein or mRNA expression levels of CA125 and markers. Results Out of 135, 57 patients suffered heart failure (HF). CA125 was expressed on the epicardium. Their levels were positively related to neutrophils, monocytes, and fibroblasts-related markers and negatively to adiposity markers. Both, plasma and epicardial CA125 levels were increased in HF patients. In this group of patients, epicardial CA125 levels were positively associated with circulating and local neutrophil activity, measured by defensin 3 levels. After testing all markers between women and men in HF patients, we observed similar levels in plasma and epicardial CA125. However, higher plasma and epicardial adiposity markers and lower mesothelial marker ITLN-1 were detected in women than in men. Conclusion CA125 is expressed in epicardial cells and its higher levels in HF might explain the higher detected levels in plasma. Its association with local and peripheral neutrophils-related markers with CA125 suggests its common pathophysiological mechanism in women and men. However, high plasma and epicardial adiposity and low mesothelial marker ITNL-1 in epicardium in women might explain the differential mechanism in HF.

Transcatheter aortic valve implantation in failed bioprosthetic or native valves: a systematic review and meta analysis

Abstract Background and purpose Currently, there is no comparative assessment of pooled clinical outcomes between valve-in-valve (ViV) transcatheter aortic valve implantation (TAVI) for either failed transcatheter or surgical bioprosthetic aortic valves (TAV or SAV) and native aortic valve TAVI (NV-TAVI) for aortic stenosis. Thus, this systematic review investigated the clinical outcomes of ViV-TAVI compared with NV-TAVI. Methods A meta-analysis was conducted according to Cochrane Handbook and the PRISMA statement. A systematic literature search was performed, using EMBASE and MEDLINE from inspection to December 25, 2023, to explore the comparative outcomes between ViV-TAVI and NV-TAVI. RStudio software was used to calculate pooled odds ratio (OR) with 95% confidence intervals (CI). Random-effects model was used to allow a more conservative assessment. Results Eighteen cohort studies (n=65,350) met eligibility criteria. Studies were categorized into 2 groups according to initially implanted bioprosthetic valve: TAV-in-TAV (5 studies, n=14490) and TAV-in-SAV implantation (13 studies, n=50860). Each ViV-TAVI group was compared with NV-TAVI. TAV-in-TAV implantation: There were no significant differences in all-cause mortality or stroke rates at ≥ 12 months between groups. The follow-up period was 12 months in all studies except in one (i.e., 24 months). Sensitivity analyses, by removing that study, did not show difference for both outcomes [(OR=1.25, 95%CI: 0.72-2.18) and (OR=1.14, 95%CI: 0.59-2.20), respectively]. TAV-in-TAV implantation was associated with higher rates of permanent pacemaker (PPM) insertion (OR=1.78, 95%CI: 1.10-2.88) within 30-day of follow-up. PPM insertion rate remained higher by 34% (OR=1.34, 95%CI: 1.02-1.76) even after removing the study that reported PPM insertion during index admission. Early conversion to open heart surgery and coronary occlusion (OR=3.75, 95%CI: 0.99-1417) did not differ between groups. TAV-in-SAV implantation: TAV-in-SAV implantation did not significantly reduce the risk of all-cause mortality, but stroke risk was reduced by 19% at ≥ 12 months follow-up. Sensitivity analyses by removing the studies with 24 months follow-up yielded comparable results [(OR=0.88, 95%CI: 0.64-1.21) and (OR=0.81, 95%CI: 0.70-0.94), respectively]. TAV-in-SAV implantation was associated with lower rates of PPM insertion compared with NV-TAVI (OR=0.33, 95%CI: 0.17-0.62) within 30-day of follow-up. The risk remained significantly lower by 69% (OR=0.31, 95%CI: 0.10-0.92) upon removing the studies that reported PPM insertion during the index admission. Early conversion to open heart surgery and coronary occlusion (OR=1.88, 95%CI: 0.82-4.32) did not differ between groups. Conclusion In comparison with NV-TAVI, TAV-in-TAV implantation was associated with higher PPM insertion rates, whereas, TAV-in-SAV implantation was associated with lower stroke and PPM insertion rates without an impact on mortality.

DNMT3A CHIP-driver mutations ignite the bone marrow

Abstract Background Clonal hematopoiesis of indeterminate potential (CHIP) is an acquired, genetic cardiovascular (CV) risk factor affecting about 10% of the general population at the age of 70 years. Most CHIP-driver mutations affect the epigenetic regulator gene DNMT3A. Experimental studies suggest a causal link between CHIP and inflammation-driven atherosclerosis, but the underlying mechanisms of how few mutant clones provoke adverse clinical outcomes in patients remain obscure. Methods Single monocytes and bone marrow cells from DNMT3A-mutation carriers undergoing coronary angiography and open-heart surgery underwent RNA and genomic DNA sequencing in parallel on a single cell level. This approach enabled us to compare mutant and non-mutant cells directly within carriers, and to non-carrier cells. Atherosclerotic chimeric mice reconstituted with a mixture of Dnmt3a-deficient (CD45.2) and -competent (CD45.1) bone marrow served as an experimental model to compare mutant to non-mutant macrophages in atherosclerotic lesions. Results Surprisingly, RNA/gDNA parallel sequencing revealed that gene expression profiles of mutant monocytes resembled those of non-mutant monocytes in carriers of DNMT3A-CHIP mutations (n=4). Collectively, however, monocytes of DNMT3A mutation carriers were more inflammatory than those of matched non-carrier patients. Mutant hematopoietic stem and progenitor cells, analyzed by RNA/gDNA parallel sequencing in two carriers, expressed more activation and inflammatory markers compared to non-mutant cells within the same bone marrow, and intraindividual differences declined as cells differentiated into monocytes. Macrophages were isolated from atherosclerotic aortas of mixed bone marrow chimeric mice based on CD45.1 (non-mutant) or CD45.2 (mutant or non-mutant controls) expression and subjected to single cell RNA sequencing. Inflammation markers were higher expressed in non-mutant macrophages within carrier mice than in non-mutant macrophages of non-carrier chimeras, and showed relatively small differences compared to Dnmt3a-deficient macrophages. Conclusions Our experimental findings in humans and mice support a pathomechanistic model in which few DNMT3A-CHIP mutation-carrying hematopoietic stem cells stimulate non-mutant cells within the bone marrow, thereby augmenting inflammation downstream in all circulating monocytes and their progeny in atherosclerotic lesions.

Risk factors of 30-day mortality following cardiac surgery in adults with congenital heart disease: analysis from the Japanese registry

Abstract Background With advancements in pediatric therapies, the adult congenital heart disease (ACHD) population has grown consistently. ACHD patients often face complications necessitating cardiac surgery, and understanding surgical risk factors is essential. Purpose This study aims to assess ACHD surgical risk factors using big data, addressing evidence gaps in previous research limited to univariate analysis due to few perioperative adverse events. Methods We analyzed the Japanese Registry of All Cardiac and Vascular Diseases-Diagnosis Procedure Combination (JROAD-DPC) database from April 2013 to March 2020. The JROAD-DPC database covers nearly all teaching hospitals with cardiovascular beds participation in JROAD. Our study included ACHD patients (&amp;gt;15 years) undergoing open-heart surgery. Our primary outcome was 30-day mortality. We assessed clinical backgrounds, admission status, treatment, and length of hospital stay. Results Out of 13,677 ACHD patients (mean age: 53 years, females 47%) undergoing cardiac surgery assessed for 30-day mortality, 13,516 (98.8%) patients were categorized into the survival group and 161 (1.2%) into the death group. Mortality rates varied by complexity of congenital heart disease (CHD): 0.8% for simple, 1.8% for moderate, and 0.9% for great. The figure shows that a significant increase in 30-day mortality rates with age was demonstrated in simple and moderate complexity (p&amp;lt;0.001 for trend analysis in both categories). In contrast, for cases of great complexity, the increase in 30-day mortality rates with aging was not statistically significant (p=0.443). The death group was significantly older and had higher rates of ambulance admissions, renal disease, and peripheral vascular disease. Intra-aortic balloon pumps (IABP), veno-arterial extracorporeal membrane oxygenation (VA-ECMO), and dialysis during hospitalization were significantly higher among deceased patients. Length of ICU stay was significantly longer in the death group (median [IQR]; 3 [2-4] vs. 6 [3-11], p&amp;lt;0.001). Cox proportional-hazards model showed that age, moderate complexity, emergency admission, hospital bed counts, renal disease, and use of IABP and VA-ECMO were independently associated with 30-day mortality (Table). Conclusions The present study, which utilizes the nationwide administrative DPC database, demonstrates that surgical outcomes for patients with ACHD, as measured by 30-day mortality rates, are generally favorable. These outcomes significantly depend on factors such as age, complexity of CHD, emergency admissions, hospital capacity, renal disease, and use of mechanical circulatory support.

Semaglutide modulates adipogenic differentiation and extracellular acidification in epicardial (EAT) and subcutaneous (SAT) adipose tissue stromal cells from patients with cardiovascular disease

Abstract Backround Cardiovascular disease (CVD) is the main cause of death in the world. One of the known risk factors is the epicardial fat (EAT) accumulation, which is around the myocardium and coronaries playing a paracrine role over them. Although mature and functional adipocytes are involved in energy balance and glucose metabolism, the hypertrophic state increases the production of fatty acid binding protein 4 (FABP4), which is a pro-inflammatory adipokine, with consequences on extracellular acidification. Recent data shows that glucagon-like peptide receptor agonists 1 (GLP1ra) drug improves the insulin response and reduces EAT thickness. Although GLP1ra has a direct effect on hypothalamus for reducing food intake, this drug might play a direct role on adipogenesis process in this fat stromal cells. Purpose Our study aims to demonstrate the effect of semaglutide on adipogenesis and metabolism in epicardial and subcutaneous stromal cells from patients with cardiovascular disease. Methods The study was approved by the Galician Research Ethics Committee, and subcutaneous adipose tissue (SAT) and EAT samples from 17 patients were obtained undergoing open-heart surgery with informed consent. Stromal cells from biopsies were isolated and cultured. Adipogenesis was induced for 15 days with or without 1 nM semaglutide, given by Novo-Nordisk (Bagsværd, Denmark), using an adipogenesis cocktail. Cells were lysed and RNA was isolated for RT-qPCR. Target genes were amplified for Glucagon like peptide 1- receptor (GLP1R), differentiation, adipogenesis, glucose metabolism and cellular markers. Extracellular acidification rate was measured with glycolytic rate assay on Seahorse. Lipids accumulation was tested by AdipoRed staining. Results Stromal cells from both tissues express GLP1R but higher differentiation factor (PGC1α) was detected in SAT compared to EAT (p=0.02), as well as adipogenesis induction. After semaglutide treatment, we observed a downregulation of FABP4 and GLUT1 in EAT (p=0.01 and p=0.02, respectively). Despite FABP4 was not modulated on SAT, there was a reduction of PGC1α levels. (p=0.02). Since glitazones upregulate PGC1α, which is used for adipogenesis induction, these results might suggest the counteract mechanism of semaglutide. The metabolism assay showed that semaglutide reduces extracellular acidification rate in EAT cells (p=0.04) and oxidative glycolysis with semaglutide treatment (p=0.003) but not in SAT cells. Conclusions Semaglutide reduces adipogenesis, through modulation of PGC1α transcription factor in EAT from patients with cardiovascular disease and extracellular acidification and oxidative glycolysis. These results might help to understand one of the mechanisms associated with EAT reduction in patients with semaglutide treatment.