Valve Surgery Research Articles

Fault Detection Technology for Ultrapure Water Plant using Virtual Sensors for Pressure Control Valve and Indicators in Return Line

Objectives:This study aims to propose a technology that utilizes virtual sensors to quickly and accurately diagnose faults in valves and measurement devices that may occur in the return line of an ultrapure water plant.Methods:The empirical equations were derived, and the error range was calculated using operational data collected from three pieces of equipment (pressure control valve, pressure transmitter, and flow transmitter) in the recovery system of the ultrapure water process. Based on this, a virtual sensor is established.Results and Discussion:It was confirmed that the utilization of 24-hour data collected from the operation of the ultrapure water plant was enough to establish virtual sensors and could also estimate monthly data with high accuracy. In Phase 1, the fault diagnosis technology was found to estimate values more accurately and had a meaningful margin of error compared to Phase 2.Conclusion:It was possible to develop a fault detection technology using the virtual sensor derived from the empirical equation. The technology showed high performance in detecting anomalies in the flow meter and pressure control valve opening but had limitations in estimating consistently pressure values. Additionally, considering that there was no issue in estimating monthly data using the equations derived using 24 hours operational data. The fault detection algorithm could be used continuously if the empirical equations are updated by collecting a day's data when operating conditions change.

Mid-regional pro-adrenomedullin is an independent predictor of cardiovascular outcomes in cardiac surgery, a prospective cohort study in 500 patients

Abstract Background MR-proADM (mid-regional pro-adrenomedullin) is a stable pro-peptide of Adrenomedullin, which is expressed in various cell types such as heart, lung, and renal tissue. It is a prognostic parameter for heart failure (HF) and sepsis as well as all-cause and cardiovascular (CV) mortality. Purpose Considering the characteristics of MR-proADM as a reliable biomarker for adverse events, we aimed to investigate the prognostic impact of MR-proADM in patients undergoing elective cardiac surgery. Methods We prospectively enrolled patients undergoing elective cardiac bypass and/or valve surgery at the department of cardiac surgery between May 2013 and August 2018. Blood samples were taken one day prior to surgery. MR-proADM was measured using an automated immunofluorescence assay. Patients were followed prospectively until endpoints were reached. The primary endpoint was the composite of hospitalization for heart failure (HHF) or CV mortality, the secondary endpoint was postoperative atrial fibrillation (POAF). The multivariate regression model was adjusted for age, sex, NT-proBNP, type of surgery, and CRP-level at baseline. Results A total of 500 patients (146 female [29.2%]; median age 69.8 years [IQR 60.6-75.5]) were followed over a median of 4.6 years (IQR 3.0–5.8). Valve surgery was performed in 214 (42.8%) patients, 160 (32%) underwent a bypass operation and 126 (25.2%) a combined valve and bypass surgery. The median MR-proADM value of the entire study population was 0.58 nmol/L (IQR: 0.44-0.79 nmol/L). Patients were stratified in risk categories based on their MR-proADM values (Low Risk ≤0.63nmol/L, Intermediate Risk 0.63-0.83nmol/L, High Risk >0.84nmol/L). Patients in the highest category presented with higher rates of diabetes mellitus (p <0.001), COPD (p <0.001), HF (p=0.009) and either bypass surgery (p=0.039) or the combination of bypass and valve surgery (p=0.008), compared to patients in the lowest tertile. We observed a significant increase in 5-year’s event rates for HHF/ CV Mortality in patients in higher risk groups (Low Risk 8.6% vs High Risk 37.7%, p <0.001, Figure 1). The adjusted Cox regression model found that MR-pro ADM was independently associated with a risk increase for HHF/ CV Mortality (adjusted HR of 4.45, 95% CI 2.55-8.09; p<0.001, Figure 2) comparing the High Risk to the Low Risk Group. A comparable risk increase could be observed in POAF, with an adjusted HR of 2.61 (High Risk Group vs Low Risk Group, 95% CI 1.46-4.67, p<0.001). Conclusion Within the prospective investigation, MR-pro ADM was found to be an independent predictor for HHF and CV mortality in patients undergoing cardiac bypass and/or valve surgery. Furthermore, there was a consistent predictive potential for POAF. In the era of personalized medicine, preoperative MR-pro ADM levels could help to identify patients at risk for serious adverse events, in order to apply intensified secondary prevention and reduce mortality and morbidity.

Postoperative heart valve infection, when and which bacteria: a nationwide cohort study

Abstract Background In patients undergoing heart valve surgery, subsequent bacteremia and infective endocarditis are feared events due to the associated high mortality. Knowledge on the incidence and specification of bacteremia following left-sided valve surgery are sparse and may have implications for prophylactic strategies and follow-up. Purpose To examine the six months incidence of bacteremia and infective endocarditis following left-sided heart valve surgery. Methods In the period from January 2010 to December 2021 all patients undergoing left-sided valve surgery were identified using Danish nationwide registries. Patients were followed until a maximum of six months, end of study, emigration, death, or outcome of interest (i.e., bacteremia or infective endocarditis). Cumulative incidence curves were computed with death as a competing risk stratified on bacterial species and for subgroups of interest: type of valve surgery, age, and sex. Results A total of 14,305 patients were included in the study. The majority of the study population were male (68.6%), and the median age was 70.2 years (25th-75th percentile 62.0-76.0 years). In total, 10,469 (73.2%) of the study population underwent aortic valve surgery, 3,497 (24.5%) underwent mitral valve surgery, while 339 (2.4%) underwent surgery on both valves. The cumulative incidence of bacteremia at six months of follow-up was 2.4% (95% CI 2.2-2.7%), Figure 1. For the overall study population, the most frequently occurring bacteremia was with Coagulase-negative Staphylococci (28%) and Staphylococcus aureus (14%). Within 30 days 0.35% of the patients had bacteremia with coagulase-negative staphylococci while this was 0.68% at six months of follow-up. For Staphylococcus aureus this was 0.19% and 0.34%, respectively. The cumulative incidence of infective endocarditis at six months of follow up was 1.0% (95% CI 0.8-1.2%). The majority of the infective endocarditis incidents were blood culture negative (27%) or caused by Enterococci (19%), Streptococci (17%) or Coagulase-negative Staphylococci (17%) while Staphylococcus aureus accounted for 14%. In crude analysis, simultaneous surgery on the mitral and aortic valve was associated with a statistically significant higher rate of bacteremia (P=0.004). Similarly, higher age was associated with a statistically significant higher rate of bacteremia (P<0.001). On the contrary, in crude analysis, no difference in the risk of bacteremia was found between sexes (P=0.9). Conclusions Bacteremia following left-sided heart valve surgery occurred in little over 2%. The majority was with Staphylococci, and half of these occurred within 30 days of the surgery. There is a continued need to optimize prophylactic strategies.

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<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<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<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 < 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.

The mechanical environment regulates the extent of aortic valve calcification and thickness: an ex vivo whole mouse heart study

Abstract Background Aortic stenosis (AS) is a narrowing of the aortic valve opening due to calcification and thickening of the leaflets. Calcifications are mostly located at regions with high mechanical stress and disturbed flow suggesting that mechanical environment is important in the regulation of calcification. However, direct evidence linking valve calcification and mechanical stress is still lacking. Recently, we established an ex vivo calcification model for whole mouse hearts (Miniature Tissue Culture System MTCS) which allows the study of the mechanical environment underlying aortic valve calcification. Purpose Aim of this study was to investigate the role of mechanical stress on aortic valve calcification and thickening using the MTCS. Methods Whole mouse hearts were cultured in the MTCS with 2 distinct configurations: 1) medium flowing from the aorta towards the aortic valve to create a continuous closed aortic valve (n=28) and 2) medium flowing from the left ventricle through the aortic valve towards the aorta to create a continuous open aortic valve (n=17) (Figure1). The hearts were subjected to low (300 ul/min) or high (3000 ul/min) flow speed in the presence of calcifying medium (3mM phosphate buffer). After culture for 1 week, the hearts were isolated and fixed overnight with 4% PFA/PBS. Alizarin red staining was performed to determine calcification presence. Quantifications were performed using Caseviewer software. Results Aortic valves in closed configuration exposed to a high flow speed, exhibited significant increase in calcification compared to aortic valves in the closed configuration exposed to low flow speed or aortic valve cultured in the open position (p<0.01, Figure2A). Of interest, the extent of calcification in the aortic valve in closed position exposed to high flow speed strongly correlated with the diameter of the aortic annulus (R²=0.86, p<0.0001, Figure2B). Conversely, leaflet thickness was significantly lower in the closed aortic valve configuration as compared with the open aortic valves configuration (p<0.05, p<0.001, Figure2C). Conclusion Our study demonstrates the influence of mechanical environment on aortic valve calcification and thickening. The presence of calcification in the closed but not the open aortic valve configuration exposed to high flow suggests that increased pressure promotes calcification. The correlation of the extent of aortic valve calcification with the diameter of the aortic annulus implies that configuration of the valve is an important determinator of calcification, with potential implications for the results of aortic valve repair. The presence of a minimal amount of mechanical stress as experienced by aortic valves in the open position, however, resulted in thicker aortic valves, indicating that the right balance of mechanical stresses is required to maintain normal valve morphology. These findings provide valuable insights into AS pathogenesis, guiding future therapeutic approaches.ex vivo cultured aortic valvesCalcification in ex vivo aortic valves

Clinical outcomes according to clinical and surgical risk scores for tricuspid regurgitation

Abstract Background TRIO score, the clinical risk score in significant tricuspid regurgitation (TR), and TRI-SCORE, the surgical mortality risk for tricuspid valve (TV) surgery, have been proposed. We aimed to investigate the correlation and distribution of two risk scores, and to define the clinical benefit of TV surgery in patients with low or intermediate TRIO score and TRI-SCORE. Methods In a total of 10,054 patients diagnosed with moderate to severe TR between January 2008 to December 2020, TRIO score and TRI-SCORE were stratified into low, intermediate, and high-risk groups. Patients of all etiologies of TR were included and patients who underwent prior tricuspid valve surgery were excluded. The clinical outcome was all-cause death. Results TRI-SCORE and TRIO scores were moderately correlated (r =0.39, p<0.001). 9,104 (90.6%) patients (age 67 ± 14 years, 42% male) had low or intermediate TRI and TRIO score. During 12.6 ± 10.1 years, 885 (9.7%) underwent TV surgery and 1,268 (13.9%) experienced clinical outcomes. Kaplan-Meier analysis revealed significant differences in clinical outcomes according to TV surgery in both low and intermediate TRIO score patients (log-rank, p<0.001) and sub-analyzed them according to the TRI-SCORE group (Figure). In multivariable Cox regression analysis, TV surgery (HR 0.37, 95% CI 0.28-0.49, p<0.001) were significantly associated with clinical outcomes after adjusting confounding factors. Conclusions TV surgery is clinically beneficial in moderate to severe TR patients with a low or intermediate TRIO score and TRI-SCORE.

Predictors of progression to significant atrial functional tricuspid regurgitation in patients with paroxysmal or persistent atrial fibrillation

Abstract Background Atrial functional tricuspid regurgitation (atrial TR) has received growing recognition as a TR entity with a distinct cause owing to its independence from valvular tethering as the predominant mechanism underlying TR. Atrial fibrillation (AF) is highly prevalent in patients with AFTR and is considered a major contributor to its development. However, evidence on predictors of progression to significant atrial function TR in patients with diagnosed AF is lacking. Methods At a single tertiary university hospital, we studied 11445 patients who underwent echocardiograms at least 1 year apart between 2010 and 2023. Patients with moderate or greater TR at the initial examination (n=432) were excluded to ensure that only subjects with confirmed progression to atrial functional TR were included. Only those with EF > 50%, no other moderate or severe valve stenosis or regurgitation, no valve surgery, and RVSP < 40mmHg were subsequently identified (n= 8159). Patients diagnosed with AF 3 months before or after the echocardiogram were included. The final analysis included 629 patients, 44 progressed to moderate or worse TR during follow-up. Results The mean age of the patients was 68 (62-74) years and 57% were male. The mean time to progression to severe TR was 5.7 years. There was no difference in left ventricle size, ejection fraction of LV, right atrium, and right ventricle size on the initial echocardiogram between the group that progressed to significant TR (group 1) and the group that did not progress (group 2). LA diameter (LAAP), LAV(LA volume), and LAVi were significantly larger in group 1. In particular, the Kaplan-Meier graph of TR progression divided into two groups based on LAV 75ml and LAVi 45ml/m2 showed a significant difference, and in particular, LAVi was a significant predictor compared to other factors. Conclusion In patients with AF, the most common cause of atrial functional TR, an initial LAVi >45ml/m2 was shown to be a predictor of progression to significant TR.cumulative survival rate

Surveillance of surgical site infections using artificial intelligence

Abstract Background Surgical site infection (SSI) is a major health problem associated with high morbidity and mortality, the consequences of which can be very serious for the patient and costly for the organisation. Surveillance systems provide insight into the incidence of SSI, the analysis of which enables improvement plans to be established to reduce it. Traditionally, surveillance systems have been based on manual medical record review for evidence of the presence of surgical infection. Objectives To create and validate a global SSI diagnostic algorithm and to optimise the SSI workload of Preventive Medicine services. Methods The study population included patients undergoing surgical procedures of rectal surgery, colon surgery, knee replacement surgery, hip replacement surgery, coronary bypass and valve surgery, at the Hospital Universitario Vinalopó in Elche (n = 1240). Data mining was used to collect clinical, microbiological and postoperative follow-up values from the electronic medical record. Machine Learning techniques were used to train (n = 1054) and validate the model (n = 186). Time spent on SSI surveillance of the preventive medicine service was measured. Results Model performance after validation was: sensitivity of 0.83 specificity of 0.87, accuracy of 0.87, an F1 score of 0.45, and an area under the curve of 0.87. The time spent by preventive medicine staff in identifying patients with surgical site infection decreased from 168 person-hours per procedure per quarter to 34 person-hours, a 77% reduction in the workload allocated to this task. Conclusions This project not only improves surveillance efficiency, but also optimises the workload in Preventive Medicine services very significantly. Key messages • This project improves the efficiency of surgical site infection surveillance and significantly optimises the workload in preventive medicine departments. • It makes it possible to extend surveillance to new surgical procedures and to work more intensively on preventive measures.

New insights into the pathophysiology of rheumatic valve disease based on different genetic and proteomics profiles

Abstract Introduction Rheumatic heart disease (RHD) pathogenesis is not fully understood. Purpose The protein profile in rheumatic heart disease may have a different fingerprint in the aortic and mitral valves, which results in different evolution in terms of valve damage. Methods To evaluate the genetic profile in symptomatic RHD, 4 simultaneous mitral and aortic valves were obtained during valve replacement, as well as 4 "normal" valves from cadavers (Control Group). The expression of 90 genes was evaluated using a customized RT-PCR array kit. A second experiment was carried out to evaluate proteomics. Then, 7 mitral and aortic valves, from the same patient, were also collected during valve surgery. The Control Group consisted of 6 mitral and aortic valves obtained from explanted hearts during heart transplantation due to non-valvular pathologies. Additionally, histopathological and sectoral proteomic analysis of amyloid deposits, found in some mitral and aortic valves, from the second experiment, were also reported. Results Mitral rheumatic valves exhibited higher expression of genes linked to calcification and immuno-inflammation compared to aortic rheumatic valves (Figure 1). Proteomic analysis, visualized through PCA graphs, highlighted differences in proteomic patterns. Despite having the same genetic pattern, control valves exhibited different proteomic profiles (Figure 1) Rheumatic mitral and aortic valves, even from the same individual, showed distinct proteomic fingerprint (Figure 1). A total of 49 significant proteins were identified in distinguishing healthy mitral and aortic valves from the same individual (Figure 1). The aortic valve displayed a richer extracellular matrix and higher levels of housekeeping proteins that maintain valve homeostasis compared to the mitral valve (Figure 1). The dominant proteomic pattern in valvular rheumatic disease was identified as alterations in critical mitochondrial metabolic activities related to proteostasis. (Figure 2). Particularly notable was the upregulation of pathways associated with lipid metabolism (Figure 2). Finally, amyloid deposits suggested APOA1 as a potential deposit protein in RHD (Figure 2). Conclusion The study confirms distinct constitutional differences between mitral and aortic valves affecting rheumatic disease progression. It emphasizes the role of altered proteostasis and altered proteins deposit, mitochondrial metabolic changes, and inflammatory responses in the disease's pathophysiology, highlighting the complexity of valvular rheumatic disease involvement.For the first time amyloid deposition has been reported as a likely consequence of significant disruption in valvular proteostasis and the proteins potentially comprising this deposit within a rheumatic valve.Genomic and proteomic overviewproteomic fingerprint of RHD and amyloid

Prognostic impact of left ventricular myocardial work in patients undergoing surgery for primary mitral regurgitation

Abstract Background Although left ventricular ejection fraction (LVEF) is widely used as a parameter for the assessment of LV systolic function, LVEF can overestimate LV systolic function in patients with severe mitral regurgitation (MR) due to its high load-dependency. Echocardiography-based, left ventricular myocardial work (LVMW) can assess LV function by incorporating LV afterload. Purpose This study aims to evaluate the prognostic value of LVMW indices in patients with primary MR undergoing mitral valve surgery. Methods Individuals who underwent mitral valve surgery for severe primary MR were included. All patients underwent transthoracic echocardiography before surgery. LVMW was derived from a vendor-specific package which integrates LV global longitudinal strain with sphygmomanometric blood pressure to construct pressure-strain loops during the cardiac cycle. (Figure 1) For the LVMW indices, previously-established normal values were used as thresholds. The primary endpoint was all-cause mortality after mitral valve surgery. Results A total of 309 patients (mean age 63 ± 12 years, 68% male) with severe, primary MR who underwent surgery, were included. The mean LV global work index (LVGWI) was 1977 ± 537 mmHg% and 132 (43%) patients had impaired LVGWI (≤ 1900 mmHg%). During a median follow-up of 5.0 years (interquartile range, 2.5-8.9), 27 (8.7%) patients died after mitral valve surgery. Patients with impaired LVGWI or LV GLS (≤ 20%) had lower survival rates compared to the group with preserved LVGWI (p <0.01) or LVGLS (p = 0.02), whereas there was no significant difference in the survival rate between patients with LVEF ≤ 60% and > 60%. (Figure 2) Furthermore, LVGWI ≤ 1900 mmHg% demonstrated incremental prognostic value over LVGLS (p = 0.049) for all-cause mortality. Conclusions In patients with severe, primary MR who underwent surgery, impaired pre-operative LVGWI was associated with a higher mortality risk. In addition, impaired LVGWI had incremental prognostic value over LVGLS. Based on these findings, LVMW is a promising parameter for predicting postoperative outcome and determining the optimal timing of valve surgery in patients with severe, primary MR.Fig1.Echo-derived Myocardial workFig2.Kaplan-Meier curves

Association between left atrial dysfunction and adverse outcomes after tricuspid valve surgery for atrial functional tricuspid regurgitation

Abstract Objectives To identify factors associated with clinical outcomes in patients undergoing tricuspid valve (TV) surgery for atrial functional tricuspid regurgitation (AF- TR). Methods Among 1,670 patients who underwent TV surgery between January 2000 and December 2020, we included 83 AF-TR patients (69.1±9.2 years, 50 women) who had severe TR without any cause other than atrial fibrillation. A comprehensive analysis of right ventricular (RV) and left atrial (LA) function on preoperative and postoperative echocardiography was performed. LA function was evaluated by LA emptying fraction (LAEF), LA reservoir strain, and LA stiffness index. The primary outcome was a composite of all-cause death and heart failure hospitalization during follow up after surgery. Results For a median of 39.9 (interquartile range 19.9 to 55.8) months, the primary outcome occurred in 20 (24.1%) patients. Patients with a primary outcome showed significantly lower LAEF (9.7±7.3 vs. 21.8±6.7 %, p<0.001) and LA reservoir strain, and higher LA stiffness index than those without. However, there was no difference in RV chamber size and functional parameters according to the occurrence of a primary outcome. The restricted cubic spline plot exhibited a significant relationship between LAEF and primary outcome. The low baseline LAEF (<17%) group showed a poorer outcome than the high LAEF group (log rank p<0.001). In the Cox regression analysis, the low LAEF (<17%) was independent predictor for primary outcome (adjusted hazard ratio 13.5, 95% confidence interval 3.1–58.6). Conclusion In patients undergoing TV surgery with AF-TR, preoperative LA dysfunction was independently associated with adverse outcomes.Figure1

Post-operative atrial fibrillation during cardiac rehabilitation: incidence and long-term prognostic value

Abstract Background Postoperative atrial fibrillation (POAF) represents a common complication after cardiac surgery and is associated with longer in-hospital stay and increased in-hospital death and stroke, but its long-term prognostic value, during cardiac rehabilitation (CR), remains not well understood. Purpose The study aimed to assess the incidence and long-term prognostic values of different types of POAF in a cohort of consecutive patients who undergo CR after cardiac surgery. Methods A consecutive registry of patients admitted to our CR after cardiac surgery represents the present study. POAF was defined as any episode of atrial fibrillation occurring in the post-operative period from post-intensive care unit to hospital discharge after CR; moreover, POAF types were classified as Paroxysmal POAF (early and late) and persistent (early and late). Long-term hard end-points were: cardiovascular (CV) mortality and major adverse cardiovascular and cerebrovascular events (MACCEs defined as a composite of cardiovascular death, heart failure hospitalization, non-fatal myocardial infarction, and stroke). Results A total of 2.020 patients were included, mean age was 67 years and male gender was prevalent (71%). CR post-coronary artery bypass graft (CABG) was the indication of CR in 53% of patients, cardiac valve surgery in 35%, while 11% underwent CR after CABG plus valve surgery. All patients were followed for a mean of 50 months. POAF was found in 392 patients (19.4%) divided into 36% paroxysmal POAF and 64% persistent POAF, while 7.7% had permanent atrial fibrillation (figure 1A). Overall POAF was associated with higher rates of CV death (SR 5.0% vs POAF 7.2% vs pAF 16.5%; p<0.001) and MACCEs (SR 12.4% vs POAF 19.6% vs pAF 25.2%; p<0.001 – figure 1B). By analyzing separately paroxysmal, persistent, early, and late POAF, interestingly only late POAF (both persistent or paroxysmal) was associated with a higher long-term CV risk, in particular, both late persistent and late paroxysmal were associated with a higher risk of MACCEs (late persistent: OR 1.65, p=0.004 / late paroxysmal: OR 1.98, p=0.002 – figure 1C), mainly driven by a higher rate of heart failure hospitalization. Interestingly late paroxysmal POAF showed the worst outcomes among all classified POAF (figure 1D). Conclusions POAF after cardiac surgery is associated with long-term adverse outcomes, but not all POAF have the same prognostic value. Late, rather than early, POAF (whether paroxysmal or persistent) is associated with a poor long-term prognosis after cardiac rehabilitation.Figure 1

Semaglutide improves contractile function in isolated human atrium

Abstract Background Recently, the results of the STEP-HFpEF trial were announced, in which high-dose treatment with the antidiabetic glucagon-like-peptide 1 agonist semaglutide resulted in a significant improvement of HFpEF-associated symptoms and reduction of NT-proBNP levels. Interestingly, treatment effects were independent of initial body weight and left-ventricular ejection fraction, sparking interest regarding the precise mechanism of action. Purpose We tested the effects of acute semaglutide treatment in isolated human right-atrial trabeculae. Methods Trabeculae were prepared from right atrial appendage biopsies from 32 patients undergoing elective coronary artery bypass grafting and/or valve surgery. Regular contractions were elicited by electrical field stimulation (1Hz, 5V/50ms, 37°C). Paired experiments were performed simultaneously per patient with a control group and one exposed to semaglutide (100 or 300nM). Developed tension was analysed at steady state after 30 min. Arrhythmias were defined as deviations from baseline not arising from electrical stimulation. L-type calcium channel blockade was achieved with nifedipine (2µM) in some experiments. Rapid cooling contraction was elicited to assess sarcoplasmic reticulum Ca2+ content (RCC1) by rapidly superfusing the trabeculae with chilled solution (2°C). After a short rewarming period of 10s to 37°C, RCC was repeated to assess the Na+/Ca2+ exchanger function (RCC2). Statistical analysis was conducted using paired t-test or Wilcoxon test as appropriate (for 2 groups) and one-way ANOVA with test for trend (for >2 groups). Results Exposure to semaglutide increased developed tension by over 3-fold in human atrial trabeculae in a dose-dependent manner: from 3.14±1.14 for control to 5.43±2.35mN/mm2 for 100nM semaglutide (p=0.03 vs. control) to 12.5±3.53 for 300nM semaglutide (p=0.004 vs. control, mean±SEM, fig. A-D, p=0.005 for linear trend). L-type calcium channel blockade with nifedipine blunted developed tension overall but did not abolish the effect of semaglutide (fig. E, p=0.02). In contrast, the developed tensions upon RCC1 and RCC2 were increased by semaglutide (300nM) compared to control, while the ratio of RCC2:RCC1 was elevated by semaglutide, indicating both increased SR Ca2+ reuptake and less external Ca2+ removal in the presence of semaglutide (fig. H-J). Relaxation time to 50% of baseline was unaltered (not shown), while relaxation time to 90% of baseline was mildly prolonged by semaglutide at 300 nM (fig. F). No increase in the rate of arrhythmias was observed by semaglutide treatment (fig. G). Conclusion Acute exposure of human atrial trabeculae to semaglutide results in a strong positive inotropic effect in a dose-dependent manner without increasing the propensity for arrhythmias. This effect is most likely due to increased SR Ca2+ reuptake. Treatment of heart failure patients with high-dose semaglutide can improve atrial function, which may ameliorate symptoms.

Temporal trends in mitral valve surgery in Denmark: changes in patient characteristics and outcomes from 1996 to 2021

Abstract Background Mitral valve regurgitation (MR) is associated with increased morbidity and mortality. Mitral valve surgery (MVS) is recommended in severe MR, which is the second most common cause of heart valve surgery in the Western world. Data on national practice patterns are lacking and are essential for the continuous epidemiologic surveillance of the disease. Purpose To investigate temporal trends in patient characteristics, incidence and mortality in patients undergoing MVS for MR in Denmark from 1996 to 2021. Methods Using Danish nationwide registries, we identified all patients ≥18 years undergoing MVS for MR. Patients operated due to infective endocarditis were excluded. The study population was grouped into one 6-year and four 5-year calendar bands and type of MVS (mitral valve repair, mechanical or biological valve replacement and transcatheter-edge-to-edge repair (TEER)). Temporal trends in patient characteristics were computed. Annual incidence rates were calculated while considering the total Danish population ≥18 years at risk. For one-year postoperative mortality analysis, the reverse Kaplan-Meier estimator and a multivariable Cox proportional hazard analysis were used. Results We identified 7,813 patients (median age 67.3 years, 65.6% males) undergoing MVS. Over calendar time, burden of comorbidities decreased while median age increased, Table 1. From 1996 to 2021, a stepwise increase was seen in the overall incidence rate for MVS from 3.87 [95% CI 3.32-4.51] to 7.06 [95% CI 6.34-7.58] per 100,000 person-years (p<0.001). The incidence of mechanical valve replacement statistically significantly decreased (p<0.001), while the incidence of mitral valve repair (p=0.004), biological replacement (p≤0.001) and TEER statistically increased (p=0.015), Figure 1. For the overall study period, one-year mortality was 5.0% for mitral valve repair, 12.7% for mechanical valve replacement, 15.7% for biological valve replacement and 19.0% for TEER. Demographics and one-year mortality stratified by calendar period are shown in Table 1. In the mitral valve repair group, adjusted analysis showed a stepwise statistically significant decrease in one-year mortality with HR 0.30 (95% CI 0.17-0.53, p≤0.001) in 2017-2021 as compared to 1996-2001. In the remaining surgical groups, trends were towards decreasing one-year mortality over calendar periods but did not reach statistical significance. Conclusion(s) In this Danish nationwide cohort study, we observed an increase in the incidence of overall mitral valve surgery from 1996 to 2021. The incidence of mechanical valve replacement decreased, while the incidence of mitral valve repair, biological replacement and TEER increased. Mortality rates significantly improved for mitral valve repair patients over calendar time. Continuous epidemiological surveillance of this patient group is required in an era of development in treatment guidelines, surgical methods and patient demographics.Table 1Figure 1

Clinical outcomes and impact of mitral valve surgery in atrial functional mitral regurgitation: the REVEAL-AFMR registry

Abstract Background The real-world impact and effective treatment strategies of atrial functional mitral regurgitation (AFMR) are poorly understood. The aim of this study was to investigate the prevalence, clinical characteristics, and the effectiveness of mitral valve surgery in AFMR. Methods The REal-world obserVational study for invEstigAting the prevaLence and therapeutic options for Atrial Functional Mitral Regurgitation (REVEAL-AFMR) was a retrospective cohort study conducted across 26 Japanese centers. All transthoracic echocardiography performed in 2019 were reviewed and patients with moderate or severe AFMR defined by preserved left ventricular function, dilated left atrium, and absence of degenerative valvular changes. The primary composite outcomes were heart failure hospitalization and all-cause mortality. Besides traditional multivariable regression analysis, propensity score-based time-zero matching was performed to account for immortal time bias. Results In 177,235 patients who underwent echocardiography, 8,867 had moderate or severe MR. Within this group, 1,007 were diagnosed with AFMR (mean age 78±10, 56% female, 80% atrial fibrillation). Of these, 113 underwent MV surgery, with 81% receiving concurrent tricuspid valve surgery. Patients who underwent surgery were younger but had more severe MR, larger left heart chambers, and a higher prevalence of heart failure than those who remained under medical therapy. During a median follow-up of 1050 days, 28% experienced the primary outcome, and 18% died. Despite a more severe disease status, only the surgical group showed a decrease in natriuretic peptide levels at follow-up and had significantly lower rate of the primary outcome (hazard ratio 0.43 [0.29-0.64], p<0.001 after adjustment for 25 covariates). Propensity score-based time-zero matching also indicated a lower risk of the primary outcome in the surgical group (hazard ratio 0.39 [0.20–0.78], p=0.007). Multiple sensitivity analyses yielded consistent results. Subgroup analysis suggested a significantly greater benefit of surgery for patients with severe MR than those with non-severe MR (p for interaction=0.044). Conclusions Our registry revealed that patients with AFMR are typically old with predominantly with atrial fibrillation, facing poor outcomes. MV surgery was associated with fewer adverse events, a finding that should be validated in future clinical trials.

Novel clinical method: left ventricular diastolic pressure curve by echocardiography

Abstract Background A non-invasive clinical method for construction of the systolic part of the left ventricular (LV) pressure curve was recently introduced. There is, however, no clinical method available to construct the LV diastolic pressure curve. Purpose The aim of this study was construction of patient-specific LV diastolic pressure curves from echocardiographic data and have initial validation against simultaneously acquired pressure curves by high-fidelity LV pressure catheters (micromanometers). Methods The study included 108 patients referred for diagnostic left heart catheterization due to suspected coronary artery disease. 81 patients were used as a training cohort. The construction of a diastolic pressure curve is based on a reference unitless pressure trace and seven key pressure-time diastolic events estimated in each patient. The reference diastolic pressure trace was generated from a group of 8 patients with LV pressures recorded by micromanometer. Each individual pressure trace from the reference cohort was first annotated with the occurrence of the key diastolic events: mitral valve (MV) opening, minimum LV pressure, peak of early-diastolic mitral flow velocity (E) and start and peak of atrial contraction-induced velocity (A), and MV closure. Then the temporal intervals between these events were normalized before calculating an averaged pressure curve (Figure 1, panels A-C). A patient-specific LV diastolic pressure curve was constructed by adjusting the standard curve according to estimated LV pressure at the key diastolic events (shown in Figure 1D). The estimation of the pressure-time instants is based on the LV volume temporal transient, used to estimate filling flow rate (Q=dV/dt) and flow acceleration and deceleration (dQ/dt=d2V/dt2), as well as a set of biomarkers including left atrial reservoir strain, peak systolic LV pressure, and body mass index. LV volume temporal traces were generated by combining global 2D volumes with global longitudinal strain. The ability to generate patient-specific diastolic LV pressure curves was validated in a second cohort of 7 patients studied with micromanometer-tipped catheters. Echocardiography and LV pressure were recorded from the same series of beats and recordings were done during breath-hold at end-expiration. The agreement was accessed qualitatively and considering the mean diastolic LV pressure. Results There was good agreement between measured and estimated LV diastolic pressure curves, qualitatively and quantitatively, via mean diastolic PLV: Bias 0.2 mmHg, limits of agreement <3.2 mmHg (Figure 1D-F). Conclusions The results suggest that the LV diastolic pressure curve can be estimated by echocardiography. The method needs validation in larger populations.Non-invasive diastolic LV pressure curve

Modeling Operations in System-Level Real-Time Control for Urban Flooding Reduction and Water Quality Improvement—An Open-Source Benchmarked Case

Advancements in smart sensing and control technologies enable urban drainage engineers to retrofit stormwater storage facilities with real-time control devices for mitigating stormwater in-site overflow, downstream flooding, and overloaded total suspended solids (TSS) in drainage pipes. While the smart technology can improve the performance of the static drainage systems, coordinatively controlling multiple valve and gate operations poses a significant challenge, especially at a large-scale watershed. Using a benchmark stormwater model located at Ann Arbor, Michigan, USA, we assessed the impact of different real-time control strategies (local individual downstream control and system-level multiple control) on balancing flooding mitigation at downstream outlets and TSS reduction at upstream storage units, such as detention ponds. We examined changes in peak water depth, outflow, and TSS as indicators to assess changes in water quantity and quality. The results indicate that system-level control can reduce peak water depth by up to 7.3%, reduce flood duration by up to 34%, and remove up to 67% of total suspended solids compared with a baseline uncontrolled system, with the outflow from upstream detention ponds being the most important hydraulic indicator for control strategy rule set-up. We find that system-level control does not always outperform the individual downstream controls, particularly in alleviating flooding duration at some downstream outlets. With urban growth and a changing climate, this research provides a foundation for quantifying the benefits of real-time control methods as an adaptive stormwater management solution that addresses both water quantity and quality challenges.

The impact of peptide receptor radionucleotide therapy with Lutetium-177 DOTATATE on cardiac metastases in neuroendocrine tumors

Abstract Background Cardiac metastasis from neuroendocrine tumors (NET) is rare and has been thought to potentially result in life threatening sequalae. Peptide receptor radionucleotide therapy (PRRT), such as Lutetium-177 (Lu-177) DOTATATE, has been validated as effective treatment for patients with NET who have progressed on somatostatin analogue (SSA) therapy and more recently suggested for use in SAA-naïve higher risk grade 2 and grade 3 NETs. However, Lu-177 DOTATATE therapy has been found to have potentially serious adverse effects both locally and systemically. Overall, the clinical significance of cardiac metastasis of NET, as well as the safety and efficacy of Lu-177 DOTATATE in this cohort, has not been thoroughly evaluated. Purpose This study assessed the outcomes and clinical consequences of cardiac metastatic involvement in patients with NET. Furthermore, this study investigated the safety of Lu-177 DOTATATE therapy in patients with cardiac metastases from NET. Methods All patients who underwent 68Ga-DOTATATE positron emission tomography for evaluation of NET across three tertiary centers between 2016 and 2022 were retrospectively evaluated. Patients with evidence of cardiac metastasis were further evaluated. Baseline characteristics, treatment modality, and clinical outcomes including mortality, arrhythmia or conduction disease, carcinoid heart disease, and heart failure admissions were recorded. Patients with cardiac metastases were grouped and compared based on therapeutic modality (conservative therapy with surveillance or SSA, Lu-177 DOTATATE therapy, or surgical resection of metastases). Results From 3253 patients with NET, 51 patients were identified to have cardiac metastases (mean age 66.7 ± 12.2 years, 54% male). Three patients underwent surgical resection of cardiac metastases, and in two of whom this was concomitant while undergoing valve surgery for carcinoid heart disease. Patients with cardiac metastasis had significantly higher mortality than patients without cardiac metastasis (HR 2.12, 95%CI 1.00 – 4.52, p = 0.049, Figure 1A). Median follow-up from diagnosis of cardiac metastasis was 3.64 years [IQR 1.59 – 5.64]. There was no significant difference in clinical outcomes between patients that received Lu-177 DOTATATE therapy (n = 27) and conservative therapy (n = 21). Specifically, there was no significant difference in mortality risk at five years post the diagnosis of cardiac metastasis between these groups (p = 0.47, Figure 1B). Conclusion Patients with cardiac metastasis from NETs have worse clinical outcomes than NET patients without cardiac metastatic involvement. Lu-177 DOTATATE therapy appears to be safe in patients with cardiac metastasis from NET.Figure 1AFigure 1B

Pre- and Post-Operative Cognitive Assessment in Patients Undergoing Surgical Aortic Valve Replacement: Insights from the PEARL Project

Background: Aortic valve stenosis (AVS) is a common valvular heart disease affecting millions of people worldwide. It leads to significant neurocognitive and neuropsychological impairments, impacting patients’ quality of life. Objective: The objective of this article is to identify and discuss the potential neurocognitive effects on patients with aortic stenosis before and after undergoing surgical aortic valve replacement (SAVR). Method: Our study involved the assessment of 64 patients undergoing aortic valve replacement (SAVR) using a neurocognitive evaluation comprising a battery of 11 different cognitive tests. These tests were designed to analyze the patients’ overall cognitive functioning, executive abilities, short- and long-term memory, and attentional performance. The tests were administered to patients before the aortic valve surgery (T0) and after the surgery (T1). From a statistical perspective, numerical variables are presented as means (±standard deviation) and medians (IQR), while categorical variables are presented as counts and percentages. Normality was assessed using the Shapiro–Wilk test. T0 and T1 scores were compared with the Wilcoxon signed rank test, with p < 0.05 considered significant. Analyses were performed using SAS version 9.4. Results: Conducted as part of a fully financed Italian Ministry of Health project (RF-2016-02361069), the study found that most patients showed normal cognitive functioning at baseline. Cognitive assessments showed that executive functions, attention, language, and semantic knowledge were within the normal range for the majority of participants. After SAVR, cognitive outcomes remained stable or improved, particularly in executive functions and language. Notably, verbal episodic memory demonstrated significant improvement, with the percentage of patients scoring within the normal range on the BSRT increasing from 73.4% at T0 to 92.2% at T1 (p < 0.0001). However, visuospatial and visuoconstructive abilities showed stability or slight decline, while attentional skills remained relatively stable. The Clock Drawing Test indicated the maintenance of cognitive functions. Conclusions: The findings of our study indicate a global stability in cognitive status among patients after undergoing SAVR, with significant improvement noted in verbal episodic memory. While other cognitive domains did not demonstrate statistically significant changes, these insights are valuable for understanding the cognitive effects of SAVR and can guide future research and clinical practice in selecting the most effective surgical and rehabilitative options for patients. Monitoring cognitive outcomes in patients undergoing aortic valve replacement surgery remains crucial.

Prognostic relevance of baseline right ventricular echocardiographic evaluation in patients undergoing valvular surgery with tricuspid intervention

Abstract Background Tricuspid valve (TV) intervention is frequently performed both as part of multivalvular surgery and as an isolated procedure. Tricuspid regurgitation (TR) significantly worsen right ventricular (RV) function, which is a prognostic determinant in many clinical scenarios. Purpose Our aim was to evaluate the relevance of baseline right ventricular (RV) baseline echocardiographic in the prognosis after tricuspid valve surgery (TVS). Methods Retrospective observational study of patients undergoing TVS between 2009 and 2022 in our tertiary centre. Baseline right chambers echocardiographic parameters were evaluated: RV diameters (basal, mid and longitudinal), TAPSE, fractional area change (FAC), Doppler tissue velocity of the tricuspid annulus (RVS´) and free wall- (FW-) and 4 chambers- (4C-) global longitudinal strain (GLS). Likewise, systolic pulmonary artery pressure (sPAP) and left ventricular ejection fraction (LVEF) were collected among other variables. Association of echocardiographic parameters with major clinical events at year was explored. Results Finally 273 consecutive patients (71 ± 10.5 years old, 66.7% female) that underwent valvular surgery with tricuspid intervention were included. Multivalvular procedure was performed in 81.3% (50.6% mitral and tricuspid, 25.6% mitral, aortic and tricuspid and 5.1% aortic and tricuspid) and EuroScore was 5 [3-9]. The most common TV lesion was TR (97.8%), functional in 84.2%. The main surgical technique was tricuspid annuloplasty with prosthetic ring (57.9%). Preoperative echocardiographic parameters are presented in Table. Baseline LVEF was 59 [53-65]%. The most frequent postoperative complication was low output (23.4%) and there was an overall mortality rate of 8.3% during the first year of follow-up. Postsurgical low output state was associated with vena contracta TR (0,78 vs 0,66 cm; p <0.001) and 4C-GLS ((-15.7 vs -17.3%; p= 0.03). None of the baseline echocardiographic variables was associated with early mortality. Conclusions Baseline RV echocardiographic parameters were associated with postoperative low output but not mortality. The relatively preserved RV dimensions and function in our series may explain these findings. Table. Baseline RV echocardiographic variablesTable