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Primary mitral regurgitation (MR) is a prevalent valvular heart disease. Therapy stratification for MR depends on accurate assessment of MR severity and left ventricular (LV) dimensions. While trans-thoracic echocardiography (TTE) has been the standard/preferred assessment method, cardiovascular magnetic resonance imaging (CMR) has gained recognition for its superior assessment of LV dimensions and MR severity. Both imaging modalities have their own advantages and limitation for therapy guidance. However, the differences between the two modalities for assessing/grade severity and clinical impact of MR remains unclear. This systematic review aims to evaluate the differences between TTE and CMR in quantifying MR severity and LV dimensions, providing insights for optimal clinical management. A literature search was performed from inception up to March 21st 2023. This resulted in 2,728 articles. After screening, 22 articles were deemed eligible for inclusion in the meta-analysis. The included study variables were, mitral valve regurgitation volume (MR VOL ), regurgitation fraction (MR FRAC ), LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), LV stroke volume (LVSV), and LV ejection fraction (LVEF). TTE showed a significant higher MR VOL (10.4 ml, I 2  = 88%, p = 0.002) and MR FRAC (6.3%, I 2  = 51%, p = 0.05) compared to CMR, while CMR demonstrated a higher LVEDV (21.9 ml, I 2  = 66%, p =  < 0.001) and LVESV (16.8 ml, I 2  = 0%, p =  < 0.001) compared to TTE. Our findings demonstrate substantial disparities in TTE and CMR derived measurements for parameters that play a pivotal role in the clinical stratification guidelines. This discrepancy prompts a critical question regarding the prognostic value of both imaging modalities, which warrants future research., (© 2024. The Author(s).)

Background: Left atrial volume index (LAVI) serves as a crucial marker for assessing left atrial (LA) remodeling, particularly in patients with mitral valve regurgitation (MR). Recent guidelines recommend a LAVI exceeding 60 mL/m 2 as Class IIa recommendation for mitral valve repair surgery in asymptomatic MR patients with preserved left ventricular function. Traditionally, echocardiography is the standard for assessing LAVI in MR patients. However, cardiac magnetic resonance imaging (CMR) is increasingly recognized for its more precise measurements of cardiac dimensions and volumes. But still, literature remains scarce on comparing the efficacy of both modalities in assessing LAVI measurements., Methods: This retrospective study included 168 MR patients undergoing both echocardiography and CMR assessments within a six-month period. LAVI measurements were compared using Pearson correlation and Bland-Altman plots. Patients were stratified based on MR grades, and clinical implications were assessed., Results: Mean LAVI differed significantly between echocardiography and CMR (47.1 ± 20.8 mL/m 2 versus 70 ± 20.3 mL/m 2 , p < 0.001, respectively). CMR consistently yielded higher LAVI measurements compared to echocardiography, with a mean difference of approximately 20 mL/m 2 . CMR measurements resulted in an increased incidence of patients meeting the class IIa LAVI criterion (LAVI >60 mL/m 2 ) by 37%. Variations in LAVI did not differ across MR grades., Conclusion: Echocardiography systematically underestimates LAVI compared to CMR in MR patients. While current guidelines rely on echocardiography, CMR's precision suggests the need for CMR-specific LAVI cutoff values to guide clinical management effectively. Establishing such values could refine patient stratification and timing of surgery, potentially improving clinical outcomes for MR patients., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Left ventricular assist devices (LVADs) are increasingly implanted in patients with advanced heart failure. Currently, LVAD care is predominantly concentrated at specialized tertiary care hospitals. However, the increasing workload and logistical burden for implanting centres pose significant challenges to accessing care for individual patients in remote areas. An emerging approach to LVAD patient management is the use of a shared care model (SCM), which facilitates collaboration between implanting centres and local non-implanting hospitals. This scoping review explores and synthesizes the current scientific evidence on the use of SCMs in LVAD care management. Eligible studies were identified in EMBASE, PubMed MEDLINE, Web of Science, Cochrane and Google Scholar. Findings were synthesized in accordance with PRISMA-ScR guidelines. Of the 950 records screened, five articles met the inclusion criteria. Four review articles focused on the proposed benefits and challenges of using SCMs. Main benefits included improved patient satisfaction and continuity of care. Important challenges were initial education of non-implanting centre staff and maintaining competency. One prospective study showed that absence of LVAD-specific care was associated with impaired survival and higher rates of pump thrombosis and LVAD-related infections. The use of SCMs is a promising approach in the long-term management of LVAD patients. However, sufficient evidence about the impact of SCMs on patients and the healthcare system is not currently available. Standardized protocols based on prospective studies are needed to develop safe and effective shared care for LVAD patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Background: Ablation strategies targeting fractionated or low-voltage potentials have been widely used in patients with persistent types of atrial fibrillation (AF). However, recent studies have questioned their role in effectively representing sites of conduction slowing, and thus arrhythmogenic substrates., Objectives: The authors studied the relationship between local conduction velocity (CV) and the occurrence of fractionated and/or low-voltage potentials in order to identify areas with critically slowing of conduction., Methods: Intraoperative epicardial mapping was performed during sinus rhythm. Unipolar potentials with an amplitude <1.0 mV were initially classified as low-voltage and potentials with ≥3 deflections as fractionation. A range of thresholds were also explored. Local CV was computed using discrete velocity vectors., Results: A total of 319 patients were included. Fractionated, low-voltage potentials were rare, accounting for only 0.36% (Q1-Q3: 0.15%-0.78%) of all atrial sites. Local CV at sites with fractionated, low-voltage potentials (46.0 cm/s [Q1-Q3: 22.6-72.7 cm/s]) was lowest compared with sites with either low-voltage, nonfractionated potentials (64.5 cm/s [Q1-Q3: 34.8-99.4 cm/s]) or fractionated, high-voltage potentials (65.9 cm/s [Q1-Q3: 41.7-92.8 cm/s]; P < 0.001). Slow conduction areas (CV <50 cm/s) could be most accurately identified by using a low voltage threshold (<1 mV) and a minimum of 3 deflections (positive predictive value: 54.2%-70.7%), although the overall sensitivity remained low (0.1%-1.9%)., Conclusions: Sites with fractionated, low-voltage potentials have substantially slower local CV compared with sites with either low-voltage, nonfractionated potentials or fractionated, high-voltage potentials. However, the strong inverse relationship between the positive predictive value and sensitivity of a combined voltage and fractionation threshold for slowed conduction is likely to complicate the use of these signal-based ablation approaches in AF patients., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: This systematic review investigates of Augmented Reality (AR) systems used in minimally invasive surgery of deformable organs, focusing on initial registration, dynamic tracking, and visualization. The objective is to acquire a comprehensive understanding of the current knowledge, applications, and challenges associated with current AR-techniques, aiming to leverage these insights for developing a dedicated AR pulmonary Video or Robotic Assisted Thoracic Surgery (VATS/RATS) workflow., Methods: A systematic search was conducted within Embase, Medline (Ovid) and Web of Science on April 16, 2024, following the Preferred Reporting items for Systematic Reviews and Meta-Analyses (PRISMA). The search focused on intraoperative AR applications and intraoperative navigational purposes for deformable organs. Quality assessment was performed and studies were categorized according to initial registration and dynamic tracking methods., Results: 33 articles were included, of which one involved pulmonary surgery. Studies used both manual and (semi-) automatic registration methods, established through anatomical landmark-based, fiducial-based, or surface-based techniques. Diverse outcome measures were considered, including surgical outcomes and registration accuracy. The majority of studies that reached an registration accuracy below 5 mm applied surface-based registration., Conclusions: AR can potentially aid surgeons with real-time navigation and decision making during anatomically complex minimally invasive procedures. Future research for pulmonary applications should focus on exploring surface-based registration methods, considering their non-invasive, marker-less nature, and promising accuracy. Additionally, vascular-labeling-based methods are worth exploring, given the importance and relative stability of broncho-vascular anatomy in pulmonary VATS/RATS. Assessing clinical feasibility of these approaches is crucial, particularly concerning registration accuracy and potential impact on surgical outcomes., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

An essential aspect of cardiovascular in situ tissue engineering (TE) is to ensure balance between scaffold degradation and neo-tissue formation. We evaluated the rate of degradation and neo-tissue formation of three electrospun supramolecular bisurea-based biodegradable scaffolds that differ in their soft-block backbone compositions only. Scaffolds were implanted as interposition grafts in the abdominal aorta in rats, and evaluated at different time points ( t  = 1, 6, 12, 24, and 40 weeks) on function, tissue formation, strength, and scaffold degradation. The fully carbonate-based biomaterial showed minor degradation after 40 weeks in vivo , whereas the other two ester-containing biomaterials showed (near) complete degradation within 6-12 weeks. Local dilatation was only observed in these faster degrading scaffolds. All materials showed to some extent mineralization, at early as well as late time points. Histological evaluation showed equal and non-native-like neo-tissue formation after total degradation. The fully carbonate-based scaffolds lagged in neo-tissue formation, presumably as its degradation was (far from) complete at 40 weeks. A significant difference in vessel wall contrast enhancement was observed by magnetic resonance imaging between grafts with total compared with minimal-degraded scaffolds.

Background and Aim: Congenital heart disease (CHD) is the most common birth defect with prevalence of 0.8%. Thanks to tremendous progress in medical and surgical practice, nowadays, >90% of children survive into adulthood. Recently European Society of Cardiology (ESC), American College of Cardiology (ACC)/ American Heart Association (AHA) issued guidelines which offer diagnostic and therapeutic recommendations for the different defect categories. However, the type of technical exams and their frequency of follow-up may vary largely between clinicians and centres. We aimed to present an overview of available diagnostic modalities and describe current surveillance practices by cardiologists taking care of adults with CHD (ACHD)., Methods and Results: A questionnaire was used to assess the frequency cardiologists treating ACHD for at least one year administrated the most common diagnostic tests for ACHD. The most frequently employed diagnostic modalities were ECG and echocardiography for both mild and moderate/severe CHD. Sixty-seven percent of respondents reported that they routinely address psychosocial well-being., Conclusion: Differences exist between reported current clinical practice and published guidelines. This is particularly true for the care of patients with mild lesions. In addition, some differences exist between ESC and American guidelines, with more frequent surveillance suggested by the Americans., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Hemocompatibility-related adverse events (HRAEs), particularly gastrointestinal bleeding, remain a frequent complication after left ventricular assist device (LVAD) implantation. The current study sought to describe and analyze whether early (<60 days) postoperative von Willebrand factor (VWF) activity assays predict the risk of gastrointestinal bleeding and stroke. A prospective single-center study including 74 HeartMate 3 device recipients between 2016 and 2023 was undertaken. The postoperative trajectory of the VWF profile was analyzed using linear mixed-effect models and Cox models were used to quantify associations between an early postoperative dip (≤0.7) in VWF activity assay measurements and late outcomes. Preoperatively, the mean VWF:Activity (Act)/Antigen (Ag) and VWF:Collagen Binding (CB)/Ag ratios were 0.94 (95% confidence interval [CI] = 0.81-1.02) and 0.95 (95% CI = 0.80-1.03), respectively, decreasing to 0.66 (95% CI = 0.57-0.73) and 0.67 (95% CI = 0.58-0.74) within 40 days (p < 0.05). In patients with VWF:CB/Ag and VWF:Act/Ag ratios ≤0.7 significantly more gastrointestinal bleeding (hazard ratio [HR]: 2.53; 95% CI = 1.1-5.8, and HR: 3.7; 95% CI = 1.5-9.2, respectively) and hemorrhagic stroke events (HR: 3.5; 95% CI = 1.6-7.6 and HR: 4.9; 95% CI = 2.1-11.7, respectively) were observed throughout the entire late (>60 days) postoperative period. In patients with VWF:Act/Ag ratio ≤0.7 less ischemic stroke events were observed (HR: 0.11; 95% CI = 0.01-0.85). In conclusion, VWF:Act/Ag and VWF:CB/Ag ratios ≤0.7 in the early postoperative phase can be used as biomarkers to predict HRAEs during long-term LVAD support., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the ASAIO.)

Competing Interests: Dr Sadeghi is a co-inventor of PulmoVR. Q. Mank (part-time) and A. Tuzcu are MedicalVR (Nieuw-Vennep, The Netherlands) employees. P. De Backer, A. Mottrie, and J. Hofman are Orsi Academy (Melle, Belgium) employees. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest.

Valvular heart disease (VHD) is becoming more prevalent in an ageing population, leading to challenges in diagnosis and management. This two-part Series offers a comprehensive review of changing concepts in VHD, covering diagnosis, intervention timing, novel management strategies, and the current state of research. The first paper highlights the remarkable progress made in imaging and transcatheter techniques, effectively addressing the treatment paradox wherein populations at the highest risk of VHD often receive the least treatment. These advances have attracted the attention of clinicians, researchers, engineers, device manufacturers, and investors, leading to the exploration and proposal of treatment approaches grounded in pathophysiology and multidisciplinary strategies for VHD management. This Series paper focuses on innovations involving computational, pharmacological, and bioengineering approaches that are transforming the diagnosis and management of patients with VHD. Artificial intelligence and digital methods are enhancing screening, diagnosis, and planning procedures, and the integration of imaging and clinical data is improving the classification of VHD severity. The emergence of artificial intelligence techniques, including so-called digital twins-eg, computer-generated replicas of the heart-is aiding the development of new strategies for enhanced risk stratification, prognostication, and individualised therapeutic targeting. Various new molecular targets and novel pharmacological strategies are being developed, including multiomics-ie, analytical methods used to integrate complex biological big data to find novel pathways to halt the progression of VHD. In addition, efforts have been undertaken to engineer heart valve tissue and provide a living valve conduit capable of growth and biological integration. Overall, these advances emphasise the importance of early detection, personalised management, and cutting-edge interventions to optimise outcomes amid the evolving landscape of VHD. Although several challenges must be overcome, these breakthroughs represent opportunities to advance patient-centred investigations., Competing Interests: Declaration of interests PPS is supported by a grant from the National Science Foundation (grant 1920920), is a consultant to RCE Technologies, and has equity options with RCE Technologies and Ultromics. S-PL is supported by grants from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, South Korea (grant number HI22C0154), and from the National Research Foundation of Korea, Ministry of Science and ICT, South Korea (grant number RS-2023-00208947). JKO is supported by a research grant on aortic stenosis from REDNVIA, holds royalties with Anumana, and has received consulting fees from Medtronic. JK is on the advisory board (unpaid) for Novostia and is a board member of the Heart Valve Society. AIPMS has research support from the Gravitation programme Materials-driven Regeneration (grant number 024.003.013) from the Dutch Research Council., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Postoperative atrial fibrillation (POAF) is a common phenomenon following cardiac surgery. In this study, we assessed current preventive strategies used by Dutch cardiothoracic centres, identified common views on this matter and related these to international guidelines., Methods: We developed an online questionnaire and sent it to all cardiothoracic surgery centres in the Netherlands. The questionnaire concerned the management of POAF and the use of pharmaceutical therapies (beta-blockers and calcium antagonists) and non-pharmaceutical methods (posterior left pericardiotomy, pericardial flushing and epicardial botulinum toxin type A injections). Usage of electrical cardioversions, anticoagulants and left atrial appendage closure were also enquired., Results: Of the 15 centres, 14 (93%) responded to the survey and 13 reported a POAF incidence, ranging from 20 to 30%. Of these 14 centres, 6 prescribed preoperative AF prophylaxis to their patients, of which non-sotalol beta-blockers were prescribed most commonly (57%). Postoperative medication was administered by all centres and included non-sotalol beta-blockers (38%), sotalol (24%), digoxin (14%), calcium antagonists (13%) and amiodarone (10%). Only 2 centres used posterior left pericardiotomy or pericardial flushing as surgical manoeuvres to prevent POAF. Moreover, respondents expressed the need for guidance on anticoagulant use., Conclusion: Despite the use of various preventive strategies, the reported incidence of POAF was similar in Dutch cardiothoracic centres. This study highlights limited use of prophylactic amiodarone and colchicine, despite recommendations by numerous guidelines, and restricted implementation of surgical strategies to prevent POAF., (© 2024. The Author(s).)

Imaging is one of the cornerstones in diagnosis and management of infective endocarditis, underlined by recent guidelines. Echocardiography is the first-line imaging technique, however, computed tomography (CT) has a class I recommendation in native and prosthetic valve endocarditis to detect valvular lesions in case of possible endocarditis and to detect paravalvular and periprosthetic complications in case of inconclusive echocardiography. Echocardiography has a higher diagnostic accuracy than CT in detecting valvular lesions, but not for diagnosing paravalvular lesions where CT is superior. Additionally, CT is useful and recommended by guidelines to detect extracardiac manifestations of endocarditis and in planning surgical treatment including assessment of the coronary arteries. The advent of photon-counting CT and its improved spatial resolution and spectral imaging is expected to expand the role of CT in the diagnosis of infective endocarditis. In this review, we provide an overview of the current role of CT in infective endocarditis focusing on image acquisition, image reconstruction, interpretation, and diagnostic accuracy., (© 2023 The Author(s).)

Objectives: Our goal was to evaluate gender representation among session leaders and abstract presenters at European cardio-thoracic surgical annual meetings., Methods: We did a descriptive study of the gender distribution among session leaders and abstract presenters at 2 European cardio-thoracic international meetings from 2017 to 2022. Data from publicly available programmes were used to generate a list of session leaders and abstract presenters. The primary outcome was to evaluate the proportion of female sessions leaders at the annual meetings. Descriptive analyses were performed including the Cochran-Armitage trend test for linear trend of proportions., Results: A total of 1025 sessions of 11 annual meetings of the European Association for Cardio-Thoracic Surgery (EACTS) and the European Society of Thoracic Surgeons were examined. A total of 397 (13.2%) out of 3007 total session leaders and 955 (15.2%) out of 6251 abstract presenters were female. From 2017 to 2022, the proportions of both female session leaders and abstract presenters trended significantly [10.4% to 21.9% (P < 0.001) and 13.7% to 18.3% (P < 0.001), respectively]. The EACTS female members and female meeting attendees significantly increased from 2017 to 2022 [11.1% to 15.9% (P < 0.001) and 23.7% to 26.9% (P < 0.001)], respectively. Most of the women attendees at the EACTS and the European Society of Thoracic Surgeons meetings who were session leaders and speakers came from Germany, Italy, the United Kingdom and the United States., Conclusions: Women are under-represented compared to men in leadership and speaking roles at European cardio-thoracic surgical annual meetings. In the past few years, an encouraging positive trend over time for female leadership roles has been noted; as a result, the proportion of female society members is represented at the annual meetings. However, a substantial gender gap still exists in leading roles of meeting attendees., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Treatment decisions in healthcare often carry lifelong consequences that can be challenging to foresee. As such, tools that visualize and estimate outcome after different lifetime treatment strategies are lacking and urgently needed to support clinical decision-making in the setting of rapidly evolving healthcare systems, with increasingly numerous potential treatments. In this regard, microsimulation models may prove to be valuable additions to current risk-prediction models. Notable advantages of microsimulation encompass input from multiple data sources, the ability to move beyond time-to-first-event analysis, accounting for multiple types of events and generating projections of lifelong outcomes. This review aims to clarify the concept of microsimulation, also known as individualized state-transition models, and help clinicians better understand its potential in clinical decision-making. A practical example of a patient with heart valve disease is used to illustrate key components of microsimulation models, such as health states, transition probabilities, input parameters (e.g. evidence-based risks of events) and various aspects of mortality. Finally, this review focuses on future efforts needed in microsimulation to allow for increasing patient-tailoring of the models by extending the general structure with patient-specific prediction models and translating them to meaningful, user-friendly tools that may be used by both clinician and patient to support clinical decision-making., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Pain and anxiety are common in patients undergoing cardiac surgery and percutaneous cardiac interventions. Virtual reality (VR) is an emerging non-pharmacological tool for pain and anxiety management. However, its application around cardiac procedures remains relatively unexplored. In this review, we perform a targeted non-systematic literature review to assess the current state-of-the-art of VR for pain and anxiety management in patients undergoing cardiac procedures. Contexts of interest were preprocedural, periprocedural, and postprocedural applications. Existing trials show inconsistent results. The majority of studies in the preprocedural (7 studies, n = 302), periprocedural (1 study, n = 99), and postprocedural stage (4 studies, n = 214) demonstrate significant reduction of pain and anxiety through VR distraction therapy or VR patient education. However, larger-scale trials (2 preprocedural studies [n = 233], 1 periprocedural study [n = 32], 2 postprocedural studies [n = 300]) report no effect. Current literature on effectiveness of VR for pain and anxiety management in cardiac surgery and interventional cardiology remains inconclusive., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Objectives: We investigated the predictive value of aortic valve cusp retraction, calcification, and fenestration for aortic valvuloplasty feasibility., Methods: Multicenter data were collected for 2082 patients who underwent surgical aortic valvuloplasty or aortic valve replacement. The study population had retraction, calcification, or fenestration in at least one aortic valve cusp. Controls had normal or prolapsed cusps., Results: All cusp characteristics demonstrated significantly increased odds ratios [ORs] for switch to valve replacement. This effect was strongest for cusp retraction, followed by calcification and fenestration (OR, 25.14; P ≤ .001; OR, 13.50, P ≤ .001; OR, 12.32, P ≤ .001). Calcification and retraction displayed increased odds for developing grade 4 aortic regurgitation compared with grade 0 or 1 combined on average over time (OR, 6.67; P ≤ .001; OR, 4.13; P = .038). Patients with cusp retraction showed increased risk for reintervention at 1- and 2-year follow-up after aortic valvuloplasty (hazard ratio, 5.66; P ≤ .001; hazard ratio, 3.22, P = .007). Cusp fenestration was the only group showing neither an increased risk of postoperative severe aortic regurgitation (P = .57) or early reintervention (P = .88) compared with the control group., Conclusions: Aortic valve cusp retraction, calcification, and fenestration were all related to increased rates of switch to valve replacement. Calcification and retraction were associated with recurrence of severe aortic regurgitation. Retraction was related to early reintervention. Fenestration was neither associated with recurrence of severe aortic regurgitation or reintervention. This indicates that surgeons are well able to distinguish aortic valve repair candidates in patients with cusp fenestration., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Maintaining balanced left and right cardiac outputs in a total artificial heart (TAH) is challenging due to the need for continuous adaptation to changing hemodynamic conditions. Proper balance in ventricular outputs of the left and right ventricles requires a preload-sensitive response and mechanisms to address the higher volumetric efficiency of the right ventricle., Methods: This review provides a comprehensive overview of various methods used to balance left and right ventricular outputs in pulsatile total artificial hearts, categorized based on their actuation mechanism., Results: Reported strategies include incorporating compliant materials and/or air cushions inside the ventricles, employing active control mechanisms to regulate ventricular filling state, and utilizing various shunts (such as hydraulic or intra-atrial shunts). Furthermore, reducing right ventricular stroke volume compared to the left often serves to balance the ventricular outputs. Individually controlled actuation of both ventricles in a pulsatile TAH seems to be the simplest and most effective way to achieve proper preload sensitivity and left-right output balance. Pneumatically actuated TAHs have the advantage to respond passively to preload changes., Conclusion: Therefore, a pneumatic TAH that comprises two individually actuated ventricles appears to be a more desirable option-both in terms of simplicity and efficacy-to respond to changing hemodynamic conditions., (© 2023 The Authors. Artificial Organs published by International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Pliable microfibrous, bioresorbable elastomeric heart valve prostheses are investigated in search of sustainable heart valve replacement. These cell-free implants recruit cells and trigger tissue formation on the valves in situ. Our aim is to investigate the behaviour of these heart valve prostheses when exposed to the high-pressure circulation. We conducted a 12-month follow-up study in sheep to evaluate the in vivo functionality and neo-tissue formation of these valves in the aortic position. All valves remained free from endocarditis, thrombotic complications and macroscopic calcifications. Cell colonisation in the leaflets was mainly restricted to the hinge area, while resorption of synthetic fibers was limited. Most valves were pliable and structurally intact (10/15), however, other valves (5/15) showed cusp thickening, retraction or holes in the leaflets. Further research is needed to assess whether in-situ heart valve tissue engineering in the aortic position is possible or whether non-resorbable synthetic pliable prostheses are preferred., (© 2023. The Author(s).)

Heart valve disease is a major cause of mortality and morbidity worldwide with no effective medical therapy and no ideal valve substitute emulating the extremely sophisticated functions of a living heart valve. These functions influence survival and quality of life. This has stimulated extensive attempts at tissue engineering "living" heart valves. These attempts utilised combinations of allogeneic/ autologous cells and biological scaffolds with practical, regulatory, and ethical issues. In situ regeneration depends on scaffolds that attract, house and instruct cells and promote connective tissue formation. We describe a surgical, tissue-engineered, anatomically precise, novel off-the-shelf, acellular, synthetic scaffold inducing a rapid process of morphogenesis involving relevant cell types, extracellular matrix, regulatory elements including nerves and humoral components. This process relies on specific material characteristics, design and "morphodynamism"., (© 2023. Springer Nature Limited.)

Objective: Quantitative extracellular volume fraction (ECV) mapping with MRI is commonly used to investigate in vivo diffuse myocardial fibrosis. This study aimed to validate ECV measurements against ex vivo histology of myocardial tissue samples from patients with aortic valve stenosis or hypertrophic cardiomyopathy., Materials and Methods: Sixteen patients underwent MRI examination at 3 T to acquire native T 1 maps and post-contrast T 1 maps after gadobutrol administration, from which hematocrit-corrected ECV maps were estimated. Intra-operatively obtained myocardial tissue samples from the same patients were stained with picrosirius red for quantitative histology of myocardial interstitial fibrosis. Correlations between in vivo ECV and ex vivo myocardial collagen content were evaluated with regression analyses., Results: Septal ECV was 30.3% ± 4.6% and correlated strongly (n = 16, r = 0.70; p = 0.003) with myocardial collagen content. Myocardial native T 1 values (1206 ± 36 ms) did not correlate with septal ECV (r = 0.41; p = 0.111) or with myocardial collagen content (r = 0.32; p = 0.227)., Discussion: We compared myocardial ECV mapping at 3 T against ex vivo histology of myocardial collagen content, adding evidence to the notion that ECV mapping is a surrogate marker for in vivo diffuse myocardial fibrosis., (© 2023. The Author(s).)

Medical students in the Netherlands have a relatively low exposure to cardiothoracic surgery and cardiology. This results in discrepancies between starting levels of medical residents and expected standards in clinical practice. Another side effect is the international decline in interest in a career in these cardiovascular fields. To compensate for this, extracurricular education programs focused on cardiothoracic surgery and cardiology have been set up. This study aims to evaluate the impact and benefits of an extracurricular education program on students' knowledge of cardiothoracic surgery and cardiology and to explore possible factors involved in (academic) career decision making. 66 participants were enrolled in the extracurricular education program VECTOR and were included in a cross-sectional cohort study. All participants scored their familiarity with different aspects of cardiothoracic surgery and cardiology prior to and after the course. Data was analyzed using Linear regression and Wilcoxon Signed Rank testing. Participants demonstrated a significant trend towards improved familiarity with cardiothoracic surgery and cardiology after the program (p = < .001). Significant increased knowledge scores were reported for all specified subdomains after the course with an increase in academic interest in cardiology (p = < .001) and cardiothoracic surgery (p = < .001). Students revealed that clinical responsibilities and a healthy work-life balance were considered most important when deciding upon their future career. This study highlights the benefit of an extracurricular education program in cardiothoracic surgery and cardiology for undergraduates and could possibly aid students in preparing for clinical practice., (© 2023. The Author(s).)

Objectives: Differences in indication and technique make a randomised comparison between valve-sparing root replacement (VSRR) and personalised external aortic root support (PEARS) challenging. We performed a propensity score (PS)-matched comparison of PEARS and VSRR for syndromic root aneurysm., Methods: Patients in the PEARS 200 Database and Aortic Valve Insufficiency and ascending aorta Aneurysm InternATiOnal Registry (undergoing VSRR) with connective tissue disease operated electively for root aneurysm <60 mm with aortic regurgitation (AR) <1/4 were included. Using a PS analysis, 80 patients in each cohort were matched. Survival, freedom from reintervention and from AR ≥2/4 were estimated using a Kaplan-Meier analysis., Results: Median follow-up was 25 and 55 months for 159 PEARS and 142 VSRR patients. Seven (4.4%) patients undergoing PEARS required an intervention for coronary injury or impingement, resulting in one death (0.6%). After VSRR, there were no early deaths, 10 (7%) reinterventions for bleeding and 1 coronary intervention. Survival for matched cohorts at 5 years was similar (PEARS 98% vs VSRR 99%, p=0.99). There was no difference in freedom from valve or ascending aortic/arch reintervention between matched groups. Freedom from AR ≥2/4 at 5 years in the matched cohorts was 97% for PEARS vs 92% for VSRR (p=0.55). There were no type A dissections., Conclusions: VSRR and PEARS offer favourable mid-term survival, freedom from reintervention and preservation of valve function. Both treatments deserve their place in the surgical repertoire, depending on a patient's disease stage. This study is limited by its retrospective nature and different follow-ups in both cohorts., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Background: Patients with mitral regurgitation (MR) commonly suffer from left atrial (LA) remodeling. LA fibrosis is considered to be a key player in the LA remodeling process, as observed in atrial fibrillation (AF) patients. Literature on the presence and extent of LA fibrosis in MR patients however, is scarce and its clinical implications remain unknown. Therefore, the ALIVE trial was designed to investigate the presence of LA remodeling including LA fibrosis in MR patients prior to and after mitral valve repair (MVR) surgery., Methods: The ALIVE trial is a single center, prospective pilot study investigating LA fibrosis in patients suffering from MR in the absence of AF (identifier NCT05345730). In total, 20 participants will undergo a CMR scan including 3D late gadolinium enhancement (LGE) imaging 2 week prior to MVR surgery and at 3 months follow-up. The primary objective of the ALIVE trial is to assess the extent and geometric distribution of LA fibrosis in MR patients and to determine effects of MVR surgery on reversed atrial remodelling., Implications: This study will provide novel insights into the pathophysiological mechanism of fibrotic and volumetric atrial (reversed) remodeling in MR patients undergoing MVR surgery. Our results may contribute to improved clinical decision making and patient-specific treatment strategies in patients suffering from MR., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 el Mathari, Kluin, Hopman, Bhagirath, Oudeman, Vonk, Nederveen, Eberl, Klautz, Chamuleau, van Ooij and Götte.)

Objectives: Our goal was to evaluate the outcome of valve-sparing root replacement (VSRR) and to compare the outcomes to those of patients having composite valve-graft conduit aortic root replacement (CVG-ARR) in a cohort of patients with aortic root aneurysm ± valve insufficiency, without valvular stenosis. Although valve-sparing procedures are preferable in young patients, there is a lack of comparative data in comparable patients., Methods: The VSRR procedures were performed in 2005 patients, and 218 patients underwent a CVG-ARR procedure. Exclusion criteria included aortic dissection, endocarditis and valvular stenosis. Propensity score matching (3:1 ratio) was applied to compare VSRR (reimplantation 33% and remodelling 67%) and CVG-ARR., Results: We matched 218 patients with CVG-ARR to 654 patients with VSRR (median age, 56.0; median follow-up was 4 years in both groups; interquartile range 1-5 years). Early mortality was 1.1% of those who had VSRR versus 2.3% in those who had CVG-ARR. Survival was 95.4% [95% confidence interval (CI) 94-97%] at 5 years in patients who had VSRR versus 85.4% (95% CI 82-92%) in those who had CVG-ARR; P = 0.002. Freedom from reintervention at 5 years was 96.8% (95% CI 95-98%) with VSRR and 95.4% (95% CI 91-99%) with CVG-ARR (P = 0.98). Additionally, there were more thromboembolic, endocarditis and bleeding events in the patients who had CVG-ARR (P = 0.02)., Conclusions: This multicentre study shows excellent results after valve-sparing root replacement in patients with an ascending aortic aneurysm with or without valve insufficiency. Compared to composite valve-graft aortic root replacement, survival is better and valve-related events are fewer. Consequently, valve-sparing procedures should be considered whenever a durable repair is feasible. We advocate a valve-sparing strategy even in more complex cases when performed in experienced centres., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Tissue-engineered heart valves (TEHVs) are emerging alternatives to current valve prostheses and prospectively a lifelong replacement. Calcification, a pathological complication for biological protheses, has been reported in preclinical TEHV studies. Systematic analysis of its occurrence is missing. This review aims to: 1) systematically review reported calcification of pulmonary TEHVs in large-animal studies; and 2) analyze the influence of engineering methodology (choice of scaffold material, cell preseeding) and animal model (animal species and age) on calcification. Baseline analysis included 80 studies, of which 41 studies containing 108 experimental groups were included in meta-analysis. Inclusion was low because only 55% of studies reported on calcification. Meta-analysis showed an overall average calcification event rate of 35% (95% CI: 28%-43%). Calcification was more prominent ( P = 0.023) in the arterial conduit region (34%; 95% CI: 26%-43%) than in the valve leaflets (21%; 95% CI: 17%-27%), and was mostly (42% in leaflets, 60% in conduits) present in a mild form. Time-analysis showed an initial surge within 1 month after implantation, decreased calcification between 1 and 3 months, and then progression over time. There were no significant differences in degree of calcification between TEHV strategy nor animal models. Much variability between individual studies was observed in degree of calcification as well as quality of analysis and reporting thereof, hampering adequate comparisons between studies. These findings underline the need for improved analysis and better reporting standards of calcification in TEHVs. It also necessitates control-based research to further enlighten the risk of calcification for tissue-engineered transplants compared to current options. This can bring the field of heart valve tissue engineering forward toward safe clinical use., Competing Interests: This research was financially supported by the Gravitation Program “Materials Driven Regeneration,” funded by the Netherlands Organization for Scientific Research (024.003.013), and the More Knowledge with Fewer Animals program by ZonMw (Practice in Synthesis of Evidence grant 114024119). Dr Akiva has received support from the Netherlands Organization for Scientific Research through a VENI grant (VI.Veni.192.094). Dr Bouten is a shareholder of Xeltis BV. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

Competing Interests: Conflict of interest: All authors are part of the HybridHeart consortium and declare no competing interests.

Many patients with end-stage heart disease die because of the scarcity of donor hearts. A total artificial heart (TAH), an implantable machine that replaces the heart, has so far been successfully used in over 1,700 patients as a temporary life-saving technology for bridging to heart transplantation. However, after more than six decades of research on TAHs, a TAH that is suitable for destination therapy is not yet available. High complication rates, bulky devices, poor durability, poor biocompatibility and low patient quality of life are some of the major drawbacks of current TAH devices that must be addressed before TAHs can be used as a destination therapy. Quickly emerging innovations in battery technology, wireless energy transmission, biocompatible materials and soft robotics are providing a promising opportunity for TAH development and might help to solve the drawbacks of current TAHs. In this Review, we describe the milestones in the history of TAH research and reflect on lessons learned during TAH development. We summarize the differences in the working mechanisms of these devices, discuss the next generation of TAHs and highlight emerging technologies that will promote TAH development in the coming decade. Finally, we present current challenges and future perspectives for the field., (© 2022. Springer Nature Limited.)

Objectives: Root reimplantation has been the favoured approach for patients with heritable aortic disorder requiring valve-sparring root replacement. In the past few years, root remodelling with annuloplasty has emerged as an alternative to root reimplantation in the general population. The aim of this study was to examine the late outcomes of patients with heritable aortic disorder undergoing valve-sparring root replacement and compare different techniques., Methods: Using the AVIATOR registry (Aortic Valve Insufficiency and ascending aorta Aneurysm InternATiOnal Registry), data were collected from 5 North American and European centres. Patients were divided into 4 groups according to the technique of valve-sparing used (root reimplantation, root remodelling with ring annuloplasty, root remodelling with suture annuloplasty and root remodelling alone). The primary endpoints were freedom from aortic regurgitation (AR) ≥2 and freedom from reintervention on the aortic valve. Secondary endpoints were survival and changes in annular dimensions over time., Results: A total of 237 patients were included in the study (reimplantation = 100, remodelling + ring annuloplasty = 76, remodelling + suture annuloplasty = 34, remodelling alone = 27). The majority of patients had Marfan syndrome (83%). Preoperative AR ≥2 was present in 41% of the patients. Operative mortality was 0.4% (n = 1). No differences were found between techniques in terms of postoperative AR ≥2 (P = 0.58), reintervention (P = 0.52) and survival (P = 0.59). Changes in aortic annulus dimension were significantly different at 10 years (P < 0.05), a difference that started to emerge 4 years after surgery., Conclusions: Overall, valve-sparring root replacement is a safe and durable procedure in patients with heritable aortic disorder. Nevertheless, root remodelling alone is associated with late annular dilatation. The addition of an annuloplasty, however, results in similar freedom from AR, reintervention, survival and changes in annulus size compared to reimplantation., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: The European Society of Thoracic Surgeons and the European Association for Cardio-Thoracic Surgery designed a questionnaire to assess the impact of gender bias on a cardiothoracic surgery career., Methods: A 46-item survey investigating gender bias was designed using online survey software from December 2020 to January 2021. All European Society of Thoracic Surgeons and European Association for Cardio-Thoracic Surgery members and non-members included in the mailing lists were invited to complete an electronic survey. Descriptive statistics and a comparison between gender groups were performed., Results: Our overall response rate was 11.5% (1118/9764), of which 36.14% were women and 63.69% were men. Women were more likely to be younger than men (P < 0.0001). A total of 66% of the women reported having no children compared to only 19% of the men (P < 0.0001). Only 6% of women vs 22% of men were professors. More women (72%) also reported never having been a formal mentor themselves compared to men (38%, P < 0.0001). A total of 35% of female respondents considered leaving surgery because of episodes of discrimination compared to 13% of men; 67% of women said that they experienced being unfairly treated due to gender discrimination. Of the male surgeons, 31% reported that they were very satisfied with their career compared to only 17% of women (P < 0.0001)., Conclusions: Women in cardiothoracic surgery reported significantly high rates of experiences with bias that may prevent qualified women from advancing to positions of leadership. Efforts to mitigate bias and support the professional development of women are at the centre of newly formed European committees., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

In the last 25 years, numerous tissue engineered heart valve (TEHV) strategies have been studied in large animal models. To evaluate, qualify and summarize all available publications, we conducted a systematic review and meta-analysis. We identified 80 reports that studied TEHVs of synthetic or natural scaffolds in pulmonary position (n = 693 animals). We identified substantial heterogeneity in study designs, methods and outcomes. Most importantly, the quality assessment showed poor reporting in randomization and blinding strategies. Meta-analysis showed no differences in mortality and rate of valve regurgitation between different scaffolds or strategies. However, it revealed a higher transvalvular pressure gradient in synthetic scaffolds (11.6 mmHg; 95% CI, [7.31-15.89]) compared to natural scaffolds (4,67 mmHg; 95% CI, [3,94-5.39]; p = 0.003). These results should be interpreted with caution due to lack of a standardized control group, substantial study heterogeneity, and relatively low number of comparable studies in subgroup analyses. Based on this review, the most adequate scaffold model is still undefined. This review endorses that, to move the TEHV field forward and enable reliable comparisons, it is essential to define standardized methods and ways of reporting. This would greatly enhance the value of individual large animal studies., Competing Interests: The authors have declared that no competing interests exist.

Background: Proton magnetic resonance spectroscopy ( 1 H-MRS) of the human heart is deemed to be a quantitative method to investigate myocardial metabolite content, but thorough validations of in vivo measurements against invasive techniques are lacking., Purpose: To determine measurement precision and accuracy for quantifications of myocardial total creatine and triglyceride content with localized 1 H-MRS., Study Type: Test-retest repeatability and measurement validation study., Subjects: Sixteen volunteers and 22 patients scheduled for open-heart aortic valve replacement or septal myectomy., Field Strength/sequence: Prospectively ECG-triggered respiratory-gated free-breathing single-voxel point-resolved spectroscopy (PRESS) sequence at 3 T., Assessment: Myocardial total creatine and triglyceride content were quantified relative to the total water content by fitting the 1 H-MR spectra. Precision was assessed with measurement repeatability. Accuracy was assessed by validating in vivo 1 H-MRS measurements against biochemical assays in myocardial tissue from the same subjects., Statistical Tests: Intrasession and intersession repeatability was assessed using Bland-Altman analyses. Agreement between 1 H-MRS measurements and biochemical assay was tested with regression analyses., Results: The intersession repeatability coefficient for myocardial total creatine content was 41.8% with a mean value of 0.083% ± 0.020% of the total water signal, and 36.7% for myocardial triglyceride content with a mean value of 0.35% ± 0.13% of the total water signal. Ex vivo myocardial total creatine concentrations in tissue samples correlated with the in vivo myocardial total creatine content measured with 1 H-MRS: n = 22, r = 0.44; P < 0.05. Likewise, ex vivo myocardial triglyceride concentrations correlated with the in vivo myocardial triglyceride content: n = 20, r = 0.50; P < 0.05., Data Conclusion: We validated the use of localized 1 H-MRS of the human heart at 3 T for quantitative assessments of in vivo myocardial tissue metabolite content by estimating the measurement precision and accuracy., Level of Evidence: 2 TECHNICAL EFFICACY STAGE: 2., (© 2021 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC. on behalf of International Society for Magnetic Resonance in Medicine.)

Sheep are a commonly used and validated model for cardiovascular research and, more specifically, for heart valve research. Implanting a heart valve on the arrested heart in sheep is complex and is often complicated by difficulties in restarting the heart, causing significant on-table mortality. Therefore, optimal cardioprotective management during heart valve implantation in sheep is essential. However, little is known about successful cardioprotective management techniques in sheep. This article reports our experience in the cardioprotective management of 20 female sheep that underwent surgical aortic valve replacement with a stented tissue-engineered heart valve prosthesis. During this series of experiments, we modified our cardioprotection protocol to improve survival. We emphasize the importance of total body hypothermia and external cooling of the heart. Furthermore, we recommend repeated cardioplegia administration at 20 min intervals during surgery, with the final dosage of cardioplegia given immediately before the de-clamping of the aorta. To reduce the number of defibrillator shocks during a state of ventricular fibrillation (VF), we have learned to restart the heart by reclamping the aorta, administering cardioplegia until cardiac arrest, and de-clamping the aorta thereafter. Despite these encouraging results, more research is needed to finalize a protocol for this procedure.

Background: In response to an increased need for patient information in congenital heart disease, we previously developed an online, evidence-based information portal for patients with congenital aortic and pulmonary valve disease. To assess its effectiveness, a stepped-wedge cluster randomised trial was conducted., Methods: Adult patients and caregivers of paediatric patients with congenital aortic and/or pulmonary valve disease and/or tetralogy of Fallot who visited the outpatient clinic at any of the four participating centres in the Netherlands between 1 March 2016-1 July 2017 were prospectively included. The intervention (information portal) was introduced in the outpatient clinic according to a stepped-wedge randomised design. One month after outpatient clinic visit, each participant completed a questionnaire on disease-specific knowledge, anxiety, depression, mental quality of life, involvement and opinion/attitude concerning patient information and involvement., Results: 343 participants were included (221 control, 122 intervention). Cardiac diagnosis (p=0.873), educational level (p=0.153) and sex (p=0.603) were comparable between the two groups. All outcomes were comparable between groups in the intention-to-treat analyses. However, only 51.6% of subjects in the intervention group (n=63) reported actually visiting the portal. Among these subjects (as-treated), disease-specific knowledge (p=0.041) and mental health (p=0.039) were significantly better than in control subjects, while other baseline and outcome variables were comparable., Conclusion: Even after being invited by their cardiologists, only half of the participants actually visited the information portal. Only in those participants that actually visited the portal, knowledge of disease and mental health were significantly better. This underlines the importance of effective implementation of online evidence-based patient information portals in clinical practice., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

In situ tissue engineering that uses resorbable synthetic heart valve scaffolds is an affordable and practical approach for heart valve replacement; therefore, it is attractive for clinical use. This study showed no consistent collagen organization in the predefined direction of electrospun scaffolds made from a resorbable supramolecular elastomer with random or circumferentially aligned fibers, after 12 months of implantation in sheep. These unexpected findings and the observed intervalvular variability highlight the need for a mechanistic understanding of the long-term in situ remodeling processes in large animal models to improve predictability of outcome toward robust and safe clinical application., Competing Interests: This research forms part of the iValve-II project, powered by Health∼Holland, top sector Life Sciences and Health (Grant number TTTI1403B), supported by the Dutch Ministry of Economic Affairs. This work was supported by the Netherlands Cardiovascular Research Initiative (CVON 2012-01): The Dutch Heart Foundation, Dutch Federation of University Medical Centers, the Netherlands Organization for Health Research and Development, the Royal Netherlands Academy of Sciences, and by the Gravitation Program “Materials Driven Regeneration,” funded by the Netherlands Organization for Scientific Research (024.003.013). Dr. Aikawa is supported by grants from the National Institutes of Health (R01 HL114805, R01 HL136431, R01 HL147095). Dr. Bouten is a shareholder of Xeltis BV. Drs. Tristan and Mes are employees of Suprapolix BV. Dr. Brugmans is an employee of Xeltis BV. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2020 The Authors.)

This surgical heritage article provides a historical overview of the most important early advances of vascular- and valvular surgery, that lead to the development of currently used vascular- and valvular prostheses and materials. The first writings describing techniques in vascular surgery mainly focussed on hemorrhage control and date from around 1600 B.C. The strategy of vessel ligation was first mentioned in Western literature around 200 B.C. In the 18 th century, techniques of ligation were expanded towards attempts of vessel restoration. The first artificial vascular prosthesis was made in 1894. From this time on, vascular prostheses were used in animal experiments and around 1900 for the first time in humans. More than 60 years later, in 1952, the first mechanical heart valve prosthesis was implanted. Four years later, the first successful biological heart valve implantation followed. In 2000, a transcatheter heart valve was successfully implanted in a human for the first time. Over time, procedures and techniques became more efficient and effective. This led to new developments, such as the manufacturing of a tissue engineered blood vessel in 1986. Nowadays, dozens of different valve prostheses have been devised, both mechanical and biological. Still, no ideal model of vascular and heart valve prosthesis exists.

Objectives: Before new heart valves can be implanted safely in humans, animal experiments have to be performed. These animal experiments have to be clearly designed, analysed and reported to assess the accuracy and importance of the findings. We aimed to provide an overview of the reporting and methodological quality of preclinical heart valve research., Methods: We conducted a systematic literature search on biological and mechanical pulmonary valve implantations in large animals. We used the Animals in Research: Reporting In Vivo Experiments (ARRIVE) guidelines to score the quality of reporting in each article. We compared the scores before and after the introduction of the ARRIVE guidelines (2010)., Results: We screened 348 articles, of which 31 articles were included. The included articles reported a mean of 54.7% adequately scored ARRIVE items (95% confidence interval 52.2-57.3%). We did not identify a difference in reporting quality (54.7% vs 54.8%) between articles published before and after 2010. We found an unclear (lack of description) risk of selection bias, performance bias and detection bias., Conclusions: The reporting quality of studies that implanted bioprosthetic or mechanical valves in the pulmonary position in the large animal model is not on the desired level. The introduction of the ARRIVE guidelines in 2010 did not improve the reporting quality in this field of research. Hereby, we want to emphasize the importance of clearly describing the methods and transparently reporting the results in animal experiments. This is of great importance for the safe translation of new heart valves to the clinic., Clinical Trial Registration Number: PROSPERO (CRD42019147895)., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objective: Decellularized extracellular matrix made from porcine small intestinal submucosa, commercially available as CorMatrix (CorMatrix Cardiovascular, Inc, Roswell, Ga) is used off-label to reconstruct heart valves. Recently, surgeons experienced failures and words of caution were raised. The aim of this study was to evaluate decellularized porcine small intestinal submucosa as right-sided heart valved conduit in a xenogeneic animal model., Methods: A pulmonary valve replacement was performed with custom-made valved conduits in 10 lambs and 10 sheep (1 month [3 lambs and 3 sheep], 3 months [3 lambs and 3 sheep], 6 months [4 lambs and 4 sheep]). Valve function was assessed after implantation and before the animal was put to death. Explanted conduits were inspected macroscopically and analyzed using immunohistochemistry and scanning electron microscopy. They also underwent mechanical testing and testing for biochemical composition., Results: All valved conduits were successfully implanted. Five sheep and 2 lambs died due to congestive heart failure within 2 months after surgery. In the animals that died, the valve leaflets were thickened with signs of inflammation (endocarditis in 4). Five sheep and 8 lambs (1 month: 6 out of 6 animals, 3 months: 4 out of 6 animals, 6 months: 3 out of 8 animals) survived planned follow-up. At the time they were put to death, 5 lambs had significant pulmonary stenosis and 1 sheep showed severe regurgitation. A well-functioning valve was seen in 4 sheep and 3 lambs for up to 3 months. These leaflets showed limited signs of remodeling., Conclusions: Fifty percent of sheep and 20% of lambs died due to valve failure before the planned follow-up period was complete. A well-functioning valve was seen in 35% of animals, albeit with limited signs of tissue remodeling at ≤3 months after implantation. Further analysis is needed to understand the disturbing dichotomous outcome before clinical application can be advised., (Copyright © 2020. Published by Elsevier Inc.)

For in situ tissue engineering (TE) applications it is important that implant degradation proceeds in concord with neo-tissue formation to avoid graft failure. It will therefore be valuable to have an imaging contrast agent (CA) available that can report on the degrading implant. For this purpose, a biodegradable radiopaque biomaterial is presented, modularly composed of a bisurea chain-extended polycaprolactone (PCL2000-U4U) elastomer and a novel iodinated bisurea-modified CA additive (I-U4U). Supramolecular hydrogen bonding interactions between the components ensure their intimate mixing. Porous implant TE-grafts are prepared by simply electrospinning a solution containing PCL2000-U4U and I-U4U. Rats receive an aortic interposition graft, either composed of only PCL2000-U4U (control) or of PCL2000-U4U and I-U4U (test). The grafts are explanted for analysis at three time points over a 1-month period. Computed tomography imaging of the test group implants prior to explantation shows a decrease in iodide volume and density over time. Explant analysis also indicates scaffold degradation. (Immuno)histochemistry shows comparable cellular contents and a similar neo-tissue formation process for test and control group, demonstrating that the CA does not have apparent adverse effects. A supramolecular approach to create solid radiopaque biomaterials can therefore be used to noninvasively monitor the biodegradation of synthetic implants., (© 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objectives: Aortic valve disease is the most frequent indication for heart valve replacement with the highest prevalence in elderly. Tissue-engineered heart valves (TEHV) are foreseen to have important advantages over currently used bioprosthetic heart valve substitutes, most importantly reducing valve degeneration with subsequent reduction of re-intervention. We performed early Health Technology Assessment of hypothetical TEHV in elderly patients (≥ 70 years) requiring surgical (SAVR) or transcatheter aortic valve implantation (TAVI) to assess the potential of TEHV and to inform future development decisions., Methods: Using a patient-level simulation model, the potential cost-effectiveness of TEHV compared with bioprostheses was predicted from a societal perspective. Anticipated, but currently hypothetical improvements in performance of TEHV, divided in durability, thrombogenicity, and infection resistance, were explored in scenario analyses to estimate quality-adjusted life-year (QALY) gain, cost reduction, headroom, and budget impact., Results: Durability of TEHV had the highest impact on QALY gain and costs, followed by infection resistance. Improved TEHV performance (- 50% prosthetic valve-related events) resulted in lifetime QALY gains of 0.131 and 0.043, lifetime cost reductions of €639 and €368, translating to headrooms of €3255 and €2498 per hypothetical TEHV compared to SAVR and TAVI, respectively. National savings in the first decade after implementation varied between €2.8 and €11.2 million (SAVR) and €3.2-€12.8 million (TAVI) for TEHV substitution rates of 25-100%., Conclusions: Despite the relatively short life expectancy of elderly patients undergoing SAVR/TAVI, hypothetical TEHV are predicted to be cost-effective compared to bioprostheses, commercially viable and result in national cost savings when biomedical engineers succeed in realising improved durability and/or infection resistance of TEHV.

In cardiovascular surgery, reconstruction and replacement of cardiac and vascular structures are routinely performed. Prosthetic or biological materials traditionally used for this purpose cannot be considered ideal substitutes as they have limited durability and no growth or regeneration potential. Tissue engineering aims to create materials having normal tissue function including capacity for growth and self-repair. These advanced materials can potentially overcome the shortcomings of conventionally used materials, and, if successfully passing all phases of product development, they might provide a better option for both the pediatric and adult patient population requiring cardiovascular interventions. This short review article overviews the most important cardiovascular pathologies where tissue engineered materials could be used, briefly summarizes the main directions of development of these materials, and discusses the hurdles in their clinical translation. At its beginnings in the 1980s, tissue engineering (TE) was defined as " an interdisciplinary field that applies the principles of engineering and the life sciences toward the development of biological substitutes that restore, maintain, or improve tissue function" (1). Currently, the utility of TE products and materials are being investigated in several fields of human medicine, ranging from orthopedics to cardiovascular surgery (2-5). In cardiovascular surgery, reconstruction and replacement of cardiac and vascular structures are routinely performed. Considering the shortcomings of traditionally used materials, the need for advanced materials that can "restore, maintain or improve tissue function" are evident. Tissue engineered substitutes, having growth and regenerative capacity, could fundamentally change the specialty (6). This article overviews the most important cardiovascular pathologies where TE materials could be used, briefly summarizes the main directions of development of TE materials along with their advantages and shortcomings, and discusses the hurdles in their clinical translation., (Copyright © 2020 Durko, Yacoub and Kluin.)

Background: Radiation-associated aortic valve (AV) stenosis is frequently seen as a late sequela after thoracic radiotherapy (RT). Although the clinical relationship between thoracic radiotherapy and valvular dysfunction has been established, the process leading to accelerated aortic valve stenosis remains unclear. The aim of this study was to determine whether increased inflammatory cell infiltration, fibrosis, and calcification is present in aortic valves after radiotherapy at the time of aortic valve replacement., Methods: Stenotic aortic valve specimens from 43 patients were obtained after surgical aortic valve replacement. A total 28 patients had previously undergone radiotherapy for breast cancer or malignant lymphoma. A total 15 patients were included as control. The valve leaflets were assessed by (immuno)histochemistry for inflammatory cell composition (CD3, CD20, CD68, and CD163) and extracellular matrix changes (collagen and calcification)., Results: Aortic valve cell density after radiotherapy for lymphoma was markedly decreased when compared with other groups. Irradiated aortic valve show similar (low) degrees of late T and B lymphocyte infiltration as control valves, whereas macrophage marker CD68 was decreased after radiotherapy for breast cancer. Collagen content was increased following radiotherapy. Aortic valves of patients with lymphoma contained significantly less calcified tissue when compared with the other groups., Conclusion: High-dose radiation at a young age (patients with lymphoma) results in cell loss and premature fibrotic aortic valve stenosis as opposed to the degenerative calcific stenosis observed in patients with breast cancer. Our findings suggest a possible dose-dependent effect of radiotherapy on aortic valve fibrosis. The active presence of inflammatory cells may be limited to the acute phase after radiotherapy., (Copyright © 2019 Elsevier Inc. All rights reserved.)