Heart Valve Research Articles

Physical properties of Korean normal aortic valves based on fluid–structure interactions

Recently, numerical methods such as computational fluid dynamics (CFD), have been widely used in heart valve research. The CFD approach has fewer restrictions compared to clinical and experimental methods as it involves interpretations through computer calculations, and it can be used to predict and analyze fluids. For valve numerical analysis using CFD, the mechanical properties of the valve must be defined based on the physical properties. However, most of the existing heart valve numerical analysis studies have been conducted for westerners, and only a few studies on the same topic have focused on Asians. Thus, in this paper, we aim to determine the physical property parameters suitable for defining the mechanical properties of the normal aortic valves of Koreans over time. In this study, we used a fluid−structure interaction technique for the valve simulation and applied three representative valve characteristics presented in previous aortic valve simulation studies. Herein, the valve patency rates in case of simulation and multidetector computed tomography images were compared and analyzed through statistical techniques. Our results revealed that the physical properties, such as density (1050 kg/m3), Young’s modulus (2 MPa), and Poisson’s ratio (0.3), are like those of the Korean aortic valve over time. If hemodynamic evaluation of the Korean aortic valve is performed through simulation using these conditions, it can be effective in identifying the factors of heart valve disease.

From the INVICTUS Trial to Current Considerations: It’s Not Time to Retire Vitamin K Inhibitors Yet!

Atrial fibrillation (AF) is a common arrhythmia in clinical practice, and oral anticoagulation is the cornerstone of stroke prevention in AF. Direct oral anticoagulants (DOAC) significantly reduce the incidence of intracerebral hemorrhage with preserved efficacy for preventing stroke compared to vitamin K antagonists (VKA). However, the pivotal randomized controlled trials (RCTs) of DOAC excluded patients with valvular heart disease, especially mitral stenosis, which remains an exclusion criterion for DOAC use. The INVICTUS study was a large multicenter global RCT aimed at evaluating the role of DOAC compared to VKA in stroke prevention among patients with rheumatic valvular AF. In this study, rivaroxaban failed to prove superiority over VKA in preventing the composite primary efficacy endpoints of stroke, systemic embolism, myocardial infarction, and death. Unfortunately, the bleeding rates were not lower with rivaroxaban either. The death and drug discontinuation rates were higher in the DOAC arm. Close to the heels of the dismal results of INVICTUS, an apixaban trial in prosthetic heart valves, PROACT-Xa, was also prematurely terminated due to futility. Hence, for AF complicating moderate-to-severe mitral stenosis or prosthetic valve VKA remains the standard of care. However, DOAC can be used in patients with surgical bioprosthetic valve implantation, TAVR, and other native valve diseases with AF, except for moderate-to-severe mitral stenosis. Factor XI inhibitors represent a breakthrough in anticoagulation as they aim to dissociate thrombosis from hemostasis, thereby indicating a potential to cut down bleeding further. Multiple agents (monoclonal antibodies—e.g., osocimab, anti-sense oligonucleotides—e.g., fesomersen, and small molecule inhibitors—e.g., milvexian) have garnered positive data from phase II studies, and many have entered the phase III studies in AF/Venous thromboembolism. Future studies on conventional DOAC and new-generation DOAC will shed further light on whether DOAC can dethrone VKA in valvular heart disease.

Successful Anaesthetic Management of Triple Valve Surgery (Double Valve Replacement and Tricuspid Valve Ring Repair)- Challenges and Troubleshooting

Heart valve diseases are extensive and include double (mitral-aortic, mitral-tricuspid), or triple (mitral, aortic, and tricuspid) valvular regurgitation, stenotic or mixed lesions. The surgical correction of valvular lesions usually consists of the repair or replacement of all valves affected by a pathologic process.We present a challenging complex valvular case of a 61 year old hypothyroid female diagnosed with severe mitral stenosis with moderate mitral regurgitation, severe aortic stenosis with mild aortic regurgitation and severe tricuspid regurgitation with high pulmonary artery pressures.She successfully underwent Double valve replacement (Mitral and aortic) and Tricuspid Annuloplasty Ring repair.

Blood culture-negative endocarditis caused by Bartonella quintana in Iran.

Blood culture-negative endocarditis (BCNE) is a challenging disease because of the significant impact of delayed diagnosis on patients. In this study, excised heart valves and blood serum samples were collected from 50 BCNE patients in two central hospitals in Tehran, Iran. Sera were tested by IFA for the presence of IgG and IgM antibodies against Bartonella quintana and B. henselae. Genomic DNA extracted from the heart valves was examined for Bartonella-specific ssrA gene in a probe-based method real-time PCR assay. Any positive sample was Sanger sequenced. IgG titer higher than 1024 was observed in only one patient and all 50 patients tested negative for Bartonella IgM. By real-time PCR, the ssrA gene was detected in the valve of one patient which was further confirmed to be B. quintana. Bartonella-like structures were observed in transmission electron microscopy images of that patient. We present for the first time the involvement of Bartonella in BCNE in Iran. Future research on at-risk populations, as well as domestic and wild mammals as potential reservoirs, is recommended.

Improved Cardiac Rehabilitation Referral Rates following Coronary Artery Bypass Graft and Heart Valve Replacement in an Inner-City Veteran Population.

Cardiac rehabilitation (CR) is underutilized due to various barriers, despite its known benefits in decreasing 5-year mortality after cardiac surgery. The authors initiated a quality improvement project to identify barriers and enhance CR referral rates and participation. The team conducted a retrospective review of cardiac surgery patients from 2015 to 2022 at the Detroit Veterans Affairs. Phase 1 covered 2015-2017 (preintervention), phase 2 was the intervention period, and phase 3 covered 2018-2022 (postintervention). Appropriate CR referral was defined as within 6 months postevent. Referral rates and 1-year post-op hospitalization were assessed. Group 1 (2015-2017) had 54 male patients, 44% Black, 89% hypertensive, with a 22% CR referral rate. Group 2 (2018-2022) had 98 male patients, 64% Caucasian, mean age 73 years, with a 36% CR referral rate postintervention (P = 0.0018). One-year hospitalization decreased from 26% to 13% (P = 0.20). CR is still an underutilized tool. Provider education and complete funding of CR can improve referral rates and participation.

Patient perspectives on health care models in cardiac surgery: a qualitative evaluation

BackgroundThe implementation of ERAS represents a promising solution to improve treatment efficiency and facilitate patient involvement. This innovative care model aims to optimize recovery processes following surgeries by adopting a holistic, interprofessional approach. At our hospital, ERAS was implemented in minimally invasive heart valve surgery, offering two distinct ERAS models. Additionally, there is also the standard of care without ERAS. The objective of the study is to gain insight into patient satisfaction and perceived differences across these various care models.MethodsPatients were interviewed using semi-structured interviews approximately two to three months after undergoing surgery. The data were analysed using qualitative content analysis in accordance with the methodology proposed by Kuckartz. Four main categories were established: Preoperative care, postoperative care and communication, patient participation and involvement, and rehabilitation and post-clinical course.ResultsComprehensive preoperative education and seamless communication throughout the perioperative care journey were identified as fundamental to patient satisfaction and optimal care processes. Patients in the ERAS + model reported higher overall satisfaction with their care compared to patients in the standard of care and ERAS groups.ConclusionPreoperative education establishes the foundation for patients’ subsequent behaviours and expectations regarding their treatment. Physical activity, nutrition, and mental health are significant aspects. The active involvement and participation of patients and their families in the treatment process facilitated superior postoperative care, intensive physiotherapy, mental support, and faster recovery. A functional flow of information throughout the entire care process is vital. Moreover, having a dedicated point of contact had a beneficial impact on patients´ well-being. The integration of innovative ERAS concepts, which encompass interprofessional preoperative patient education and psychosomatic support, represents a promising approach from a patient perspective, offering benefits to a broad spectrum of cardiac surgical patients.

A Review of Biomechanical Studies of Heart Valve Flutter

This paper reviews recent biomechanical studies on heart valve flutter. The function of the heart valves is essential for maintaining effective blood circulation. Heart valve flutter is a kind of small vibration phenomenon like a flag fluttering in the wind, which is related to many factors such as a thrombus, valve calcification, regurgitation, and hemolysis and material fatigue. This vibration phenomenon is particularly prevalent in valve replacement patients. The biomechanical implications of flutter are profound and can lead to micro-trauma of valve tissue, accelerating its degeneration process and increasing the risk of thrombosis. We conducted a systematic review along with a critical appraisal of published studies on heart valve flutter. In this review, we summarize and analyze the existing literature; discuss the detection methods of frequency and amplitude of heart valve flutter, and its potential effects on valve function, such as thrombosis and valve degeneration; and discuss some possible ways to avoid flutter. These findings are important for optimizing valve design, diagnosing diseases, and developing treatment strategies.

A Risk Prediction Model for Prolonged Length of Stay After Minimally Invasive Valve Surgery.

Minimally invasive surgery determines shorter postoperative hospital length of stay (LOS) even in cardiac surgery. Potential preoperative factors affecting LOS are still not known in minimally invasive heart valve surgery (MIVS). We aimed to identify preoperative variables influencing prolonged LOS in MIVS. We reviewed 189 patients who underwent MIVS via minithoracotomy at our institution. Prolonged LOS was defined as more than 7 postoperative days. Poisson and logistic regression were used to screen the predictors. The mean postoperative LOS was 9.13 days, and 64 patients (33.9%) experienced a prolonged LOS. These patients were older, more frequently in New York Heart Association (NYHA) class III or IV, showed worse left ventricular ejection function (LVEF), and had a higher incidence of reoperation and chronic kidney disease (CKD). At univariate analysis, the most significant preoperative factors affecting prolonged LOS were age (odds ratio [OR] = 1.04), NYHA class III or IV (OR = 3.03), reduced LVEF (OR = 3.22), CKD (OR = 2.7), and redo surgery (OR = 3.6). After adjustment, the most significant preoperative factors predicting prolonged LOS were age (OR = 1.03, 95% CI: 1.01 to 1.06, P = 0.02) and redo surgery (OR = 3.33, 95% CI: 1.29 to 8.9, P = 0.01). The most important factors affecting prolonged LOS after MIVS were represented by age and redo surgery, although other preoperative characteristics such as reduced LVEF, NYHA class III or IV, and CKD play a significant role in delaying recovery after MIVS. Further larger studies are needed to better identify potential preoperative predictors of prolonged LOS after MIVS.

Relationship between clinical congestion and worsening renal function after intravenous initiation of furosemide in patients with acute heart failure.

To investigate if worsening renal function (WRF) appearing in some patients with acute heart failure (AHF) after intravenous furosemide initiation is influenced by severity of congestion. We conducted a retrospective secondary analysis of consecutive patients diagnosed with AHF and prospectively included in 10 Spanish emergency departments (EDs) for whom serum creatinine at ED arrival and after 2-7days of intravenous furosemide initiation were available. Congestion was clinically evaluated by identification of 7 signs/symptoms and by chest X-ray. The outcome was WRF, defined as a delta-creatinine ≥ 0.3mg/dL. Risk of WRF according to congestion was estimated in models adjusted by patient baseline characteristics and vitals at ED arrival, and interaction was also investigated. We included 3027 patients (median age 82years, 56% women), and 657 (21.7%) presented WRF after intravenous furosemide initiation. When signs/symptoms were individually considered, only lower limbs edema was associated with decreased risk of WRF (20.1% vs. 24.8%; OR = 0.76, 95%CI = 0.64-0.91). After adjustment, lower limbs edema persisted inversely associated with WRF (aOR = 0.78, 95%CI = 0.65-0.94), with significant lower risk for patients ≤ 80years and without chronic kidney disease, functional limitation, and hypoxemia (p for interaction 0.01, 0.04, 0.02 and 0.03, respectively). Neither degree of clinical congestion (number of signs/symptoms of congestion) nor radiological congestion in chest X-ray were related to WRF. Worsening renal function was associated with a higher 1-year all-cause mortality (40.1% vs 34.6%; HR = 1.27, 1.10-1.46; aHR = 1.331, 1.151-1.540). In patients with WRF, liver cirrhosis, chronic treatment with loop diuretics and renin-angiotensin system inhibitors, age (> 80years), dementia, heart valve disease and NYHA class III-IV were associated with higher mortality. Intravenous furosemide initiation in patients with AHF without lower limbs edema must be cautious, as they are at increasing risk of developing WRF during the next following days, which in turn is associated with a higher 1-year mortality.

Clinical Management and Pathophysiology of Infective Endocarditis: An Updated Review of Diagnostic Challenges and Therapeutic Approaches

Infective endocarditis (IE) is a severe and life-threatening condition characterized by infection of the endocardial surface of the heart, primarily affecting the heart valves. Despite advances in diagnostic techniques and antimicrobial therapies, IE remains associated with significant morbidity and mortality due to its complex pathogenesis and clinical variability. This article reviews the most recent developments in the pathophysiology, diagnostic criteria, and management strategies of infective endocarditis. Key issues such as microbial etiology, including common pathogens like Staphylococcus aureus and Streptococcus species, are discussed alongside less frequent organisms and their association with specific patient populations. The article emphasizes the importance of early diagnosis using advanced imaging modalities, such as echocardiography and PET-CT, and laboratory findings, particularly blood cultures. We explore both medical and surgical management strategies, highlighting the role of antibiotic therapy and the indications for valve surgery. A focus is given to the management of complex cases, including prosthetic valve endocarditis and infections in immunocompromised patients. The article aims to provide clinicians with a comprehensive understanding of the evolving landscape of infective endocarditis and its implications for patient outcomes.

Role of negative transthoracic echocardiography in excluding infective endocarditis

Abstract Background Recent guidelines suggest an extensive role of transesophageal echocardiography (TOE) in the diagnostic work-up for suspected infective endocarditis (IE). However, the negative predictive value of transthoracic echocardiography (TTE) remains poorly investigated. Purpose The purpose of our study was to evaluate the accuracy of TTE in ruling out IE in order to avoid unnecessary TOE, a more invasive and expensive diagnostic exam. Methods We reviewed data of 637 consecutive patients referred to our laboratory of echocardiography with a suspected diagnosis of IE who underwent TOE within 14 days of TTE (median 4.4 days; interquartile range 2.4-7.4). For each patient we obtained age, sex, blood culture results, complete blood count, blood chemistry, evidence of systemic embolism or pulmonary embolism, and presence of moderate/severe heart valve disease, congenital heart disease, valve prostheses and intracardiac devices. Patients with initial doubtful findings at TOE were referred for a follow-up TOE after one week and/or 18F fluorodeoxyglucose positron emission tomography computed tomography to achieve a definitive clinical diagnosis. Patients in whom a clear diagnosis of IE could not be achieved (n=7) were considered to have the disease. Results Of the 637 patients enrolled, 375 had negative TTE for IE (59%). TOE was positive and doubtful for IE in 44 (12%) and 29 (8%) of these patients, respectively. After further assessment, a final diagnosis of IE was achieved in 56 patients (15%). Variables associated with IE at univariable analysis included presence of valve prostheses (p<0.001), systemic or pulmonary embolism (p<0.001), lower platelet count (p=0.003), positive blood culture (p=0.005), aortic valve regurgitation (p=0.02), aortic valve stenosis (p=0.03) and mitral regurgitation (p=0.03). At multivariable logistic regression, independent predictors of IE (OR=odds ratio; CI=confidence interval) included evidence of systemic or pulmonary embolism (OR 17.75, 95% CI 6.66-47.3, p<0.001), bioprosthetic heart valves (OR 2.93, 95% CI 1.31-6.53 p=0.023) and lower platelet count (OR 0.995, 95% CI 0.991-0.998, p=0.003). Among the subgroup of patients (n=183, 49%) with no evidence of embolism, no bioprosthetic valve and platelet count >190,000/mL (median value), IE was diagnosed in 11 patients only (6%). Conclusions In our study, a negative TTE in the subgroup of patients with suspected IE showing platelet count >190,000/mL and absence of embolism and valvular bio-prosthesis, had a negative predictive value for IE of 94%, suggesting that, in this subset of patients, TOE can initially be delayed and performed only if clinical suspicion continues to remain high.

Polyphenol-treatment without preceding glutaraldehyde fixation: a potential paradigm change for bioprosthetic heart valves

Abstract Background Glutaraldehyde (GA) is the common fixative agent for bioprosthetic heart valves (BHVs). However, its chemical instability can expose calcium binding sites and, at commercially used concentrations, GA does not ensure effective immunological tolerance, triggering an immune response correlated to degeneration. Recently, polyphenols (PPs) achieved an almost complete xenoantigens inactivation in GA-fixed BHVs ensuring chemical stability of the treated tissue while improving mechanical characteristics and adding anti-infective and anti-thrombotic properties [1-4]. Purpose A new PP-based treatment has been introduced as a potential GA substitute in BHV manufacturing. The unique chemical properties of PPs permit them to interact with the tissue through stable chemical bonds without depolymerization over time, achieving several improvements that promise to extend the long-term durability of BHVs (Fig.1). Methods The study compared the effects of two cross-linking methods on bovine pericardial tissue: (1) traditional fixation in GA, and (2) treatment with PPs without GA. The type of chemical interaction between PPs and tissue was evaluated through nuclear magnetic resonance. The xenoantigens inactivation was quantified in-vitro by ELISA test and in-vivo in a humanized mouse animal model. Biomechanical properties were assessed through uniaxial stress-strain tests and cross-link density through the shrinkage temperature test. The protective effect against bacterial adhesion was evaluated against a strain of S aureus, while the inhibition of thrombosis was evaluated in-vivo in a pig animal model and in-vitro in a blood-loop using bovine blood with radio-labeled platelets. Results PPs effectuated multiple chemical bonds with and within the pericardium including cross-links based on covalent and hydrogen bonds, stacking, and electrostatic interactions. The inactivation of over 90% of surface-xenoantigens of the treated tissue allowed for superior biocompatibility (compared to <50% by commercial GA concentrations). The increase in elongation exhibited by PP-treated tissue confirmed excellent biomechanical features (Fig.2) while a sufficient degree of cross-linking was demonstrated through an adequate shrinkage temperature. Furthermore, a significant degree of bacterial adhesion (86% inhibition evaluated with S. aureus) and thrombus formation (Fig.2, up to 90% inhibition) were observed. Conclusion There is a real clinical need for improved chemical stability, calcification resistance, and immunological tolerance of current BHVs (surgical and transcatheter). PP technology may substitute the use of GA extending their performance and durability, thereby opening trans-catheter heart valves to younger patients. Reducing the need for mechanical heart valves would also address the associated risks of lifelong anticoagulation therapy.Figure 1Figure 2

Prognostic value of left atrial strain in patients with moderate to severe mitral stenosis

Abstract Background Mitral stenosis causes an inflow restriction during diastole and is characterized by an increase in left atrial (LA) pressure with reduced cardiac output. Pressure overload of the LA can lead to atrial fibrosis and remodeling, resulting in a loss of LA reservoir and compliance capacity that can lead to backward load on the pulmonary circulation. To date, there are limited studies evaluating the impact of LA strain on prognosis of mitral stenosis patients. Purpose The aim of this study was to assess the prognostic value of LA strain in patients with moderate to severe mitral stenosis using two-dimensional (2D) strain imaging. Methods This was a single-center retrospective study, 237 patients with moderate or severe mitral stenosis were enrolled from January 2010 to December 2022. Baseline clinical and echocardiographic parameters were collected, LA strain measurements with reference time point at end diastole for reservoir strain (LASr), conduit strain (LAScd) and contraction strain (LASct) were analyzed using TOMTEC software. The endpoint was a composite outcome of all-cause mortality, heart failure hospitalization and valve intervention (percutaneous transvenous mitral commissurotomy and surgical intervention). All the LA parameters were analyzed separately to avoid collinearity. Results A total of 237 patients were included in the study. The patients had a mean age was 66.56 ± 13.61 years-old and were predominantly female (67.9%) with median follow up duration is 4.54 years (IQR 1.44 – 6.44). Mean left ventricular ejection fraction (LVEF) was 56.86 ± 10.51%, mean left atrium volume index (LAVI) was 73.94 ± 55.46 ml/m2, mean for LASr, LAScd and LASct were 11.81 ± 8.89%, -6.19 ± 4.50%, and -5.58 ± 6.05% respectively. LASr with a cut-off < 15.8% was independently associated with the composite outcome of all-cause mortality, heart failure hospitalization and valve intervention on multivariable Cox regression analysis (HR 2.51, 95% CI 1.54 - 4.10, p < 0.001). LAScd, LASct and LA volume index did not demonstrate any significant association with the endpoint. Conclusion LASr was independently associated with all-cause mortality, heart failure hospitalization and valve intervention in patients with moderate to severe mitral stenosis.

Prognostic value of right ventricular-pulmonary arterial coupling indices in patients with moderate to severe mitral stenosis

Abstract Background Right ventricular-pulmonary arterial (RV-PA) coupling represents the relationship of RV contractility and RV afterload. The ability of RV to adapt to changes in RV afterload (i.e. increased pulmonary arterial (PA) loading) has prognostic implications in various cardiovascular diseases such as heart failure and pulmonary arterial hypertension. RV-PA uncoupling occurs when RV contractility cannot match RV afterload, resulting in right heart dysfunction. However, RV-PA coupling has not been investigated in mitral stenosis patients. Purpose To evaluate the prognostic significance of various non-invasive RV-PA coupling parameters (TAPSE/PASP and RVFWLS/PASP) in patients with moderate to severe mitral stenosis. Methods This was a single-center retrospective study of 237 patients with moderate or severe mitral stenosis enrolled between January 2010 to December 2022. Baseline clinical and echocardiographic parameters were collected. RV free wall longitudinal strain (RVFWLS) was subsequently analyzed using TOMTEC software. Echocardiography-derived RV-PA coupling parameters were collected, including TAPSE/PASP and RVFWLS/PASP. The primary endpoint was a composite outcome of all-cause mortality, heart failure hospitalization and valve intervention (percutaneous transvenous mitral commissurotomy and surgical intervention). RV parameters were analyzed separately to avoid collinearity. Results A total of 237 patients were included in the study. The patients had a mean age was 66.56 ± 13.61 years-old and were predominantly female (67.9%). The median follow-up duration was 4.54 years (IQR 1.44 – 6.44). Mean left ventricular ejection fraction (LVEF) was 56.86 ± 10.51%, mean TAPSE 18.29 ± 5.36 mm and mean RVFWLS was -23.60 ± 7.96 %. In separate multivariable Cox regression models after adjustment for age , sex and mitral stenosis severity, TAPSE/PASP ratio < 0.36mm/mmHg (HR 2.025 , 95% CI 1.395-2.939, p < 0.001 ) and RVFWLS/PASP ratio ≥ - 0.5%/mm Hg (HR 2.031 95% CI 1.404 – 2.938 , p< 0.001) remained independently associated with mortality , heart failure hospitalization and valve intervention. Conclusion TAPSE/PASP and RVFWLS/PASP were independently associated with all-cause mortality, heart failure hospitalization and valve intervention in patients with moderate to severe mitral stenosis.

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.

First in-human study of 64Cu-DOTATATE positron emission tomography/computed tomography(PET/CT) in infective endocarditis: a prospective head-to-head comparison with 18-FDG PET/CT

Abstract Background Infective endocarditis (IE) is a severe and potentially fatal condition, which can be challenging to diagnose. Positron emission tomography/computed tomography (PET/CT) with [18F]fluorodeoxyglucose ([18F]FDG) is proposed as a diagnostic tool in the ESC endocarditis guidelines, but holds limitations. Purpose To compare the tracer uptake between [64Cu]Cu-DOTATATE and [18F]FDG in patients with IE, and to examine sensitivity and specificity in patients with prosthetic valve endocarditis (PVE) or native valve endocarditis (NVE). Methods The CuDOS-study was a prospective study including 20 cases with IE (10 with PVE and 10 with NVE) and 20 controls. [64Cu]Cu-DOTATATE and [18F]FDG PET/CT were performed in all participants. Scans were read blinded to clinical data. Tracer uptakes were measured as maximum standardized uptake values (SUVmax) in each heart valve. A visual interpretation of the presence or absence of IE was recorded for [64Cu]Cu-DOTATATE and [18F]FDG, respectively. Results The median age of the cases and controls was 68 years [IQR 53-71] and 61 years [IQR 56-67], respectively. In cases and controls, 85% and 70% were men, respectively. [64Cu]Cu-DOTATATE uptake (median SUVmax [IQR]) in patients with IE was higher than in controls (2.38 [1.87-2.90] vs. 1.43 [1.30-1.56], p<0.001), although this difference was mainly driven by PVE-cases (2.99 [2.22-3.75] vs. 1.43 [1.30-1.56 (controls), p<0.001) and to a lesser extent the NVE-cases (1.78 [1.22-2.33] vs. 1.43 [1.30-1.56 (controls), p=0.079), Figure 1. The sensitivity of [64Cu]Cu-DOTATATE and [18F]FDG PET/CT in 20 cases and the 20 controls were comparable, and the specificity was 90% and 75%, respectively. The analysis of PVE versus the 20 controls showed equal sensitivity (80%) for [64Cu]Cu-DOTATATE and [18F]FDG PET/CT and a specificity of 90% and 75%, respectively. The difference in the specificity between [64Cu]Cu-DOTATATE and [18F]FDG was 15% [IQR -5.9-36%], p=0.38. Conclusion [64Cu]Cu-DOTATATE PET/CT showed relevant uptake in the infected valve in patients with infective endocarditis. [64Cu]Cu-DOTATATE had a numerically higher specificity than [18F]FDG in prosthetic valve endocarditis, although the difference was not statistically significant. Both tracers were limited in the detection of native valve endocarditis.Figure 1 [64Cu]Cu-DOTATATE and [18F]FDG

An epidemiological update on infective endocarditis: a two-decade retrospective longitudinal analysis

Abstract Background Infective endocarditis (IE) is a rare yet serious condition affecting the heart valves and the endocardium. Despite advances in management, IE's incidence is on the rise, maintaining a mortality rate similar to that of the late 20th century. Notably, there has been a notable shift in the risk-factor profile, transitioning from traditional factors such as rheumatic heart disease and poor dental health to more iatrogenic causes such as prosthetic heart valves, cardiac devices, foreign body implants, haemodialysis, and immunosuppression. This shift impacts microbiological and imaging diagnosis. Purpose While IE has been extensively studied in the past, the evolving landscape prompts an epidemiological re-evaluation of vulnerable patient populations and the challenges in current diagnostic parameters. Our primary objective is to examine the trends in microbiological and imaging diagnostics over two decades and to compare them across native valve endocarditis (NVE), prosthetic valve endocarditis (PVE), and cardiac implantable electronic device-related IE (CIED-IE). Methods We conducted a retrospective analysis of longitudinal data encompassing 912 patients admitted with either a possible or definite IE diagnosis between 2001 and 2023. Results The incidence of IE increased over the study duration (p<0.01) with octogenarians most affected (21%). Iatrogenic risk factors were associated with nearly two-thirds (63%) of patients diagnosed with IE, while traditional risk factors were evident in almost one-eighth (13%). Blood culture-negative endocarditis increased over the study duration (81% versus73%, p<0.01) and Staphylococcus aureus (29%, p<0.01) became the dominant pathogen over Viridans Streptococcus (14%, p=0.001). Imaging with transthoracic (56% in 2004 versus 75% in 2023) and transoesophageal echocardiography (57% in 2004 versus 79% in 2023) had an increasing contribution in the diagnosis of IE over the two decades. The subgroup analysis found PVE and CIED-IE were more likely to have negative blood cultures (OR=3.7, CI [1.2-6.8] & OR=4.9, CI [1.3-8]) compared to NVE (OR=0.04, CI [0.02-0.8]). PVE and CIED-IE were more likely to have inconclusive imaging (OR=3.7, CI [1.2-6.6] & OR=2.2, CI [0.07-7.8]) compared to NVE (OR=0.63, CI [0.3-3.2]). Complications of stroke were higher in PVE (OR=3.5, CI [0.89-10]) compared to NVE which also had a lower stroke rate (OR=.16, CI [.04-.73]). PVE had more valvular insufficiency (OR=2.1, CI [0.6-4]) compared to NVE (OR=1.2, CI [0.9-6]). The 12-month mortality was no different across the entities (OR=0.3, CI [0.5-7.7] & OR=.49, CI [0.14-1.8] & OR=0.85, CI [0.3-2.4]). Conclusion Our study underscores the evolving nature of IE, now predominantly a healthcare-related disease. Diagnostic challenges persist due to the heterogeneity of the disease, with the emergence of distinct entities such as PVE and CIED-IE.Graphs: Blood culture & echocardiographyForest plot: NVE vs PVE vs CIED-IE

Improving early mortality risk detection in light-chain cardiac amyloidosis patients with routine echocardiographic indicators and mayo staging

Abstract Background Light-chain cardiac amyloidosis (AL-CA) is a fatal cardiomyopathy caused by the deposition of monoclonal immunoglobulin light-chain in the cardiac fibers, conduction system, valves, and other parts of the heart. The Mayo 2004 staging system is widely used to assess the prognosis of AL-CA. Those in the highest-risk categories, Mayo 2004 stage IIIb, exhibit extremely poor responses to conventional treatment regimens, resulting in high early mortality rates. However, within the same stage, prognostic outcomes among patients can still vary significantly. Hence, a more detailed stratification of high-risk patients is crucial for pinpointing those at extreme risk. Objective To investigate whether conventional echocardiographic measurements can enhance the identification of high-risk patients with early mortality in AL-CA on the basis of existing risk stratification. Methods Continuous enrollment of patients diagnosed with AL-CA at our center from May 2020 to December 2022. Clinical data, echocardiography, and follow-up results of the patients were collected. Logistic regression analyses were used to identify risk factors for early mortality, with risk factor thresholds calculated using Receiver Operating Characteristic (ROC) curves. Kaplan-Meier survival analysis was employed to assess endpoint events. The diagnostic efficacy of the model was evaluated using the area under the ROC curve and the Integrated Discrimination Improvement (IDI). Results A total of 76 patients were included with an average age of 59±10 years. Among them, 51 were male (67.1%). The median follow-up duration was 10 months (ranging from 5 to 20 months). Early mortality, defined as death within 6 months, occurred in 20 patients (26.3%). Twenty-three patients were categorized under the Mayo 2004 stage IIIb (30.3%). The 6-month mortality rate for patients in the Mayo 2004 stage IIIb was 56.5%. The sensitivity of early diastolic transmitral flow velocity to early diastolic mitral annular tissue velocity ratio divided left ventricular ejection fraction [(E/e’) /LVEF] in predicting early mortality in patients with AL-CA is 63%, and the specificity is 92%.When compared to the Mayo 2004 stage IIIb alone, (E/e')/LVEF≥0.5 combined with the Mayo 2004 stage IIIb had an area under the curve of 0.731 and 0.824, respectively, in the ROC curve. The IDI was 0.113 (95% CI: 0.013-0.213, P=0.026), representing an 11.3% enhancement in the predictive value of early mortality in AL-CA patients. Conclusion Routine echocardiography derived E/e' to LVEF ratio offered added prognostic value for early mortality beyond Mayo staging.Kaplan-Meier survival curve

Systematic review and meta-analysis on the effects of physical activity-based interventions on frailty status and clinical outcomes in adults with long-term cardiac conditions

Abstract Introduction Frailty is common in patients with long-term cardiac conditions and is associated with poor clinical outcomes, but limited treatment options are available. Previous studies investigating interventions for frailty have shown positive results with physical activity interventions, however, these studies were largely based on general elderly populations. Aim To assess the impact of physical activity-based interventions on frailty and clinical outcomes in frail patients with long-term cardiac conditions. Methods A systematic review and meta-analysis was conducted based on the PRISMA guideline, using Medline, Embase, CENTRAL, PEDro, CINAHL electronic databases for articles published between 2000 and 2023. Studies which recruited adults >18 years with long-term cardiac conditions (including angina, acute coronary syndrome (ACS), valve disease, heart failure (HF), atrial fibrillation, cardiac surgery and congenital heart disease) who underwent physical activity-based interventions were included. The primary outcome was change in frailty (measured using a validated tool) post intervention. We also assessed the effect of interventions on mortality and hospitalisation. Results We screened 2697 records and reviewed 91 full-text articles; 12 studies (14 articles) were included, involving 1394 patients. Median age of participants ranged from 64 to 82 years. Five studies recruited participants with HF, 3 evaluated participants post transaortic valve implantation, 3 recruited cardiac surgical patients and 1 study evaluated participants post ACS. Physical activity-based interventions were multi-domain, including a mixture of aerobic, strength, balance, endurance and respiratory muscle training; the majority (N=10) had individualised exercise prescription. Meta-analysis of 8 randomised controlled trials (RCTs) showed statistically significant improvement in frailty associated with physical activity-based interventions compared to controls [pooled standardised mean difference (95% CI) = -0.34 (-0.59 to -0.08), p = 0.01, I2 = 48%]. Seven RCTs evaluated change in frailty by short physical performance battery (SPPB). Meta-analysis of these studies showed a statistically significant improvement in SPPB associated with physical activity-based interventions compared to controls [pooled mean difference (95% CI) = 0.83 (0.31-1.34), p = 0.002, I2 = 49%]. (Figure) The magnitude of improvement in SPPB exceeded the minimally clinically significant improvement of 0.5. Three studies evaluated the effect of physical activity-based intervention on clinical outcomes, all of which showed neutral effect on mortality and hospitalisation. Conclusion Physical activity-based interventions in patients with frailty and long-term cardiac conditions were associated with significant improvement in frailty status, with neutral effect on mortality and hospitalisation. Figure: Meta-analysis of 7 RCTs assessing effect of physical activity-based interventions on SPPB