Investigating native human cardiac tissue with preserved 3D macro- and microarchitecture is fundamental for clinical and basic research. Unfortunately, the low accessibility of the human myocardium continues to limit scientific progress. To overcome this issue, utilizing atrial appendages of the human heart may become highly beneficial. Atrial appendages are often removed during open-heart surgery and can be preserved ex vivo as living tissue with varying durability depending on the culture method. In this study, we prepared living thin myocardial slices from left atrial appendages that were cultured using an air-liquid interface system for overall 10 days. Metabolic activity of the cultured slices was assessed using a conventional methyl thiazolyl tetrazolium (MTT) assay. To monitor the structural integrity of cardiomyocytes within the tissue, we implemented our recently described super-resolution microscopy approach that allows both qualitative and quantitative in-depth evaluation of sarcomere network based on parameters such as overall sarcomere content, filament size and orientation. Additionally, expression of mRNAs coding for key structural and functional proteins was analyzed by real-time reverse transcription polymerase chain reaction (qRT-PCR). Our findings demonstrate highly significant disassembly of contractile apparatus represented by degradation of [Formula: see text]-actinin filaments detected after three days in culture, while metabolic activity was constantly rising and remained high for up to seven days. However, gene expression of crucial cardiac markers strongly decreased after the first day in culture indicating an early destructive response to ex vivo conditions. Therefore, we suggest static cultivation of living myocardial slices derived from left atrial appendage and prepared according to our protocol only for short-termed experiments (e.g. medicinal drug testing), while introduction of electro-mechanical stimulation protocols may offer the possibility for long-term integrity of such constructs.

We aimed to evaluate electrocardiogram (ECG)-gated MR angiography (MRA) in the follow-up after surgery involving the ascending aorta regarding technical feasibility, image quality, spectrum of findings, and their implications for clinical management. We retrospectively analyzed a cohort of 19 patients (median age 59 years, range 38–79 years), who underwent MRA for follow-up imaging after surgery involving the ascending aorta. Our magnetic resonance imaging protocol consisted of a time-resolved, non-ECG-gated MRA and an ECG-gated MRA performed at 3T. Median examination duration was 25 minutes (range 11–41 minutes). All examinations were assessed by 2 readers in consensus for image quality on a 5-point scale ranging from 1 (non-diagnostic) to 5 (excellent). MRA examinations and patient charts were analyzed for diagnostic findings and their consequences for further management. Subjective image quality was rated as “sufficient” (score 3.1 ± 1.1) for the aortic root and as “good” to “excellent” for the ascending aorta (score 4.5 ± 0.7), aortic arch (4.5 ± 0.7), supra-aortic branches (4.5 ± 0.6) and descending aorta (4.6 ± 0.7). Abnormal findings were seen in 6 patients (32%) including progressive diameter of remaining aneurysm or dissection (3 patients, 16%) and suture aneurysms (3 patients, 16%). In all 6 of these patients, abnormal findings at MRA had consequences for clinical management. ECG-gated MR angiography at 3T yields good image quality for post-operative surveillance after aortic surgery involving the ascending aorta. This technique may serve as an alternative to computed tomography particularly in younger patients with repeated follow-up.

The effect of monomeric glutaraldehyde fixation and amino acid detoxification on biocompatibility and tissue-guided regenerative potential of decellularized bovine pericardium was evaluated. The degree of cross-linking, porosity, enzymatic degradation, alpha-galactosyl content, the efficacy of detoxification, and cytotoxicity towards human epithelial cells were assessed. Tissue was subcutaneously implanted for eight weeks in male juvenile Sprague-Dawley rats, and mechanical properties, host cell infiltration, and calcification were evaluated. Three groups were compared i) decellularized tissue, ii) decellularized, monomeric glutaraldehyde fixed and amino acid detoxified tissue, and iii) commercial glutaraldehyde fixed non-decellularized tissue (Glycar®) (n = 6 rats per group). The fixation process gave a high degree of cross-linking (>85%), and was resistant to enzymatic degradation, with no significant effect on porosity. The detoxification process was effective, and the tissue was not toxic to mammalian cells in vitro. Tissue from both decellularized groups had significantly higher (p < 0.05) porosity and host cell infiltration in vivo. The process mitigated calcification. A non-significant decrease in the alpha-galactosyl content was observed, which increased when including the alpha-galactosidase enzyme. Mechanical properties were maintained. The fixation and detoxification process adequately removes free aldehyde groups and reduces toxicity, preventing enzymatic degradation and allowing for host cell infiltration while mitigating calcification and retaining the mechanical properties of the tissue. This process can be considered for processing decellularized bovine pericardium with tissue-guided regeneration potential for use in cardiovascular bioprostheses; however, methods of further reducing antigenicity, such as the use of enzymes, should be investigated.

Objectives: In this article, we present our initial clinical experience with staged minimally invasive direct coronary bypass (MIDCAB), percutaneous coronary intervention (PCI), and transcatheter aortic valve implantation (TAVI) in high-risk octogenarians (Hybrid). Background: The use of percutaneous techniques for managing structural heart diseases, especially in elderly high-risk patients, has revolutionized the treatment of structural heart diseases. These procedures are present predominantly being offered as isolated interventions. The feasibility, clinical benefit, and outcomes of combining these techniques with MIDCAB have not been sufficiently explored and have subsequently been underreported in the contemporary literature. Methods: Four consecutive octogenarians with severe aortic stenosis (AS) and complex coronary artery disease (CAD) that were at high risk for conventional surgery with extracorporeal circulation (ECC) were discussed in our Multidisciplinary Heart Team (MDH). Our MDH consisted of an interventional cardiologist, cardiac surgeon, and cardiac anesthesiologist. A hybrid approach with the alternative strategy comprising of MIDCAB, PCI, and TAVI in a staged fashion was agreed on. All 4 patients had both PCI/stenting and MIDCAB prior to deployment of the TAVI-prosthesis. Results: From January 2019 to December 2020, 4 consecutive patients aged between 83 and 85 (3 male/1 female) years were scheduled for MIDCAB/PCI followed by percutaneous treatment of severe symptomatic AS.Intraoperatively, one patient was converted to full sternotomy, and surgery was performed by off-pump coronary artery bypass grafting. The overall procedural success rate was 100% in all 4 patients with resolution of their initial presenting cardiopulmonary symptoms. There were no severe complications associated with all hybrid procedures. There was no 30-day mortality in all patients. All patients were discharged home with a median hospital stay ranging between 9 and 25 days. All patients have since then been followed-up regularly.There was one noncardiac-related mortality at 6-months postsurgery. All other patients were well at 1-year follow-up with improved NewYork Heart Association Class II. Conclusions: In a selected group of elderly, high prohibitive risk patients with CAD and severe symptomatic AS, a staged approach with MIDCAB and PCI followed by TAVI can be safely performed with excellent outcomes. We advocate a MDH-based preliminary evaluation of this patient cohort in selecting suitable patients and appropriate timing of each stage of the hybrid procedure.

Glutaraldehyde (GA)-fixed bovine pericardial patches remain the cardiovascular industry standard despite reports of degradation, thickening, inflammation, calcification and lack of tissue remodelling. Decellularization provides the opportunity to attenuate some of these immune-mediated processes. This study compared the mechanical and morphological integrity of bovine pericardium that is GA-fixated (Glycar® patches) or decellularized (BPS), using a proprietary protocol, following implantation in an ovine model. The impact of the processing methods on tissue strength and morphology was assessed prior to implantation. Pericardial patches were then implanted in the descending aorta and main pulmonary artery of juvenile sheep (n = 6 per group) for 180 days, and clinically evaluated using echocardiography. At explanation, patches were evaluated for strength, calcification and biological interaction. Histology demonstrated a wave-like appearance of well-separated collagen fibers for BPS scaffolds that provided pore sizes adequate to promote fibroblast infiltration. The collagen of the Glycar® patches showed loss of collagen fiber integrity, making the collagen densely compacted, contributing to insignificant recipient cell infiltration. The clinical performance of both groups was excellent, and echocardiography confirmed the absence of aneurysm formation, calcification and degeneration. Explanted Glycar® patches demonstrated cells in abundance within the fibrous encapsulation that separated the implant from the host tissue. More importantly, the fibrous encapsulation also contributed to patch thickening of both the explanted aorta and pulmonary patches. The decellularized pericardial scaffolds demonstrated recellularization, resistance to calcification, re-endothelialization and adequate strength after 180-day implantation. The proprietary decellularization protocol produced pericardial scaffolds that could be considered as an alternative to GA-fixed pericardial patches.

IntroductionThe rapid-deployment valve system (RDVS) was introduced to facility minimally invasive aortic valve replacement. In this study we evaluate the potential benefits of RDVS in elderly high-risk patients with endocarditis of the aortic valve.Materials and MethodsSince the introduction of RDVS in our institution in December 2017 through October 2021, EDWARDS INTUITY rapid-deployment prosthesis (Model 8300A, Edwards Lifesciences, Irvine, CA, USA) has been implanted in a total of 115 patients for different indications by a single surgeon. Out of one-hundred and fifteen cases of RDVS implantation, seven patients with a median age of 77 yrs. (range 62–84yrs.), suffered from active infective endocarditis of the aortic valve. The median EuroSCORE II of these highly selected patient cohort was 77% (range 19–80%). Patient data were evaluated perioperatively including intra-operative data as well as in-hospital morbidity/mortality and follow-up after discharge from hospital.ResultsThree patients underwent previous cardiac surgery. Concomitant procedures were performed in six patients including, ascending aorta replacement (n = 3), mitral valve repair (n = 1), pulmonary valve replacement (n = 1), bypass surgery (n = 1), left atrial appendix resection (n = 1) and anterior mitral valve repair (n = 1). Median aortic cross-clamp and cardiopulmonary bypass time was 56 min (range 29–122 min) and 81 min (range 45–162 min.), respectively. Post-operative complications in these elderly high-risk patients were atrial fibrillation (n = 3) and re-exploration for pericardial effusion (n = 1). One pacemaker implantation was required on postoperative day 6 due to sick sinus syndrome. There was one in-hospital death (14%) and one during follow-up (14%).ConclusionRapid-deployment aortic valve system seems to be a viable option with acceptable morbidity and mortality in elderly high-risk patients with active infective endocarditis of the aortic valve.

Homografts are routinely stored by cryopreservation; however, donor cells and remnants contribute to immunogenicity. Although decellularization strategies can address immunogenicity, additional fixation might be required to maintain strength. This study investigated the effect of cryopreservation, decellularization, and decellularization with additional glutaraldhyde fixation on the strength and structure of ovine pulmonary homografts harvested 48 h post-mortem. Cells and cellular remnants were present for the cryopreserved group, while the decellularized groups were acellular. The decellularized group had large interfibrillar spaces in the extracellular matrix with uniform collagen distribution, while the additional fixation led to the collagen network becoming dense and compacted. The collagen of the cryopreserved group was collapsed and appeared disrupted and fractured. There were no significant differences in strength and elasticity between the groups. Compared to cryopreservation, decellularization without fixation can be considered an alternative processing technique to maintain a well-organized collagen matrix and tissue strength of homografts.

Primary pulmonary artery sarcoma is an uncommon neoplasm. Given its clinical and radiographic resemblance to pulmonary embolism, initial diagnostic steps may be complicated, leading to delay in diagnosis. This report presents the case of a 52-year-old-woman who was admitted with pulmonary embolism. She underwent pulmonary embolectomy, and histopathologic examination revealed synovial sarcoma.

Papillary fibroelastomas (PFE) are benign neoplasms, mostly located on valvular surfaces with high embolic potential. This study presents a 27-year single institutional experience on surgical treatment of PFE in an adult patient- cohort with long-term follow-up. This study was approved by the institutional review board. Date and number of IRB approval: 11/23/2017, Institutional Review Board approval number A2014-0149. The need for individual patient consent was waived. We retrospectively evaluated all patients who underwent cardiac surgery for suspected space-occupying lesions in the observation period between June 1991 and June 2018 at our hospital. Clinicopathological features, imaging characteristics, surgical procedures and disease outcome were analyzed. 120 patients were diagnosed with various primary/secondary cardiac tumors and histology confirmed 21 PFEs were found in 16 patients. There was no significant age difference between patients with valvular vs nonvalvular PFEs (P = 0.26). Valvular lesions were found in aortic valve (n = 6), mitral valve (n = 2) and tricuspid valve (n = 1). Nonvalvular PFEs were found in right atrium (n = 2), left ventricle (n = 2), left atrial appendage (n = 2) and aortic wall (n = 1). Valvular lesions were significantly smaller in size compared to non-valvular lesions (P = 0.0013). Left-side PFEs were associated with a high embolization episodes (10/13 patients, 77%) not related to the size. One patient died in-hospital. All other patients were discharged out of the hospital postoperative. Follow-up was performed regularly for a median of 2.8 years (range 0.1-11 years) postoperative. Nonvalvular PFE tended to be larger in size and at least when located on the left sided heart had equally high propensity to embolize compared to valvular PFE. We strongly advocate surgical excision in all left-sided PFE.

Sir Donald N. Ross established a new era to treat aortic valve disease by introducing the Ross procedure in 1967. The original technique was complex by implanting the pulmonary valve subcoronary into the aortic root with excellent long-term results. The limited part of this specific approach however, was meanly the right ventricular outflow tract (RVOT) reconstruction. Today, the golden standard is the use of a cryopreserved pulmonary allograft, however disadvantageous such as availability and immunogenic response can eventually lead to structural valve deterioration. Tissue engineering could help to create a valve with an excellent durability including remodelling, regeneration and growth potential for RVOT reconstruction. This article reflex a recent literature overview on clinical available solutions of correcting the RVOT by the use of decellularized pulmonary allografts.

Congenital factor VII (FVII) deficiency is a rare bleeding disorder (RBD) with phenotypes ranging from asymptomatic state to life threatening bleeding episodes. There is no established recommendation for the perioperative management of patients scheduled for cardiac surgery. We have described the perioperative management of a patient with FVII deficiency treated for aortic valve stenosis, coronary artery disease, and atrial fibrillation. Balancing perioperative bleeding risk and risks of thrombotic events thereafter in such patients is difficult and requires a multidisciplinary approach.

Papillary fibroelastomas are benign tumors that usually originate from cardiac valves but may have other endocardial origins. We report the cases of 2 patients in whom left atrial appendage masses were initially diagnosed as thrombus. They were treated for embolic stroke and their symptoms resolved; however, their left atrial appendage masses did not regress. After surgery, histologic analysis of the resected masses revealed papillary fibroelastoma in both cases. We discuss the diagnostic and therapeutic dilemmas encountered in patients with papillary fibroelastomas and cardiac masses other than thrombus.

Background We present a 76-year-old poly-morbid male patient suffering from severe ischemic mitral valve regurgitation. A hybrid approach was suggested by the heart team to treat his multifaceted cardiac pathologies. Methods At first percutaneous mitral valve repair with the mitraclip device was performed to reduce surgical risk. This was then followed by minimally invasive direct coronary artery bypass (MIDCAB). Results At day 20 Post mitraclip intervention the patient suffered gastrointestinal bleeding which needed argon plasma coagulation (APC)-therapy and multiple blood transfusions. Stage II of the hybrid procedure was executed on post-intervention day 34 by minimally invasive direct coronary artery bypass (MIDCAB) to left anterior descending artery (LAD). Seven days later the patient was discharged. Up to two years of follow-up, the patient is in stable condition, without recurrent cardiac symptoms. Conclusion Hybrid approach of percutaneous mitral valve repair followed by MIDCAB is an effective minimally invasive treatment for severe ischemic mitral valve regurgitation and coronary artery disease.

Homograft availability and durability remain big challenges. Increasing the post-mortem ischaemic harvesting time beyond 24 h increases the potential donor pool. Cryopreservation, routinely used to preserve homografts, damages the extracellular matrix (ECM), contributing to valve degeneration. Decellularization might preserve the ECM, promoting host-cell infiltration and contributing towards better clinical outcomes. This study compared the performance of cryopreserved versus decellularized pulmonary homografts in the right ventricle outflow tract (RVOT) of a juvenile ovine model. Homografts (n = 10) were harvested from juvenile sheep, subjected to 48 h post-mortem cold ischaemia, cryopreserved or decellularized and implanted in the RVOT of juvenile sheep for 180 days. Valve performance was monitored echocardiographically. Explanted leaflet and wall tissue evaluated histologically, on electron microscopical appearance, mechanical properties and calcium content. In both groups the annulus diameter increased. Cryopreserved homografts developed significant (¾) pulmonary regurgitation, with trivial regurgitation (¼) in the decellularized group. Macroscopically, explanted cryopreserved valve leaflets retracted and thickened while decellularized leaflets remained thin and pliable with good coaptation. Cryopreserved leaflets and walls demonstrated loss of interstitial cells with collapsed collagen, and decellularized scaffolds extensive, uniform ingrowth of host-cells with an intact collagen network. Calcific deposits were shown only in leaflets and walls of cryopreserved explants. Young fibroblasts, with vacuoles and rough endoplasmic reticulum in the cytoplasm, repopulated the leaflets and walls of decellularized scaffolds. Young's modulus of wall tissue in both groups increased significantly. Cryopreserved valves deteriorate over time due to loss of cellularity and calcification, while decellularized scaffolds demonstrated host-cell repopulation, structural maintenance, tissue remodelling and growth potential.

This is the twelfth chapter of the guideline “Calculated initial parenteral treatment of bacterial infections in adults – update 2018” in the 2 updated version. The German guideline by the Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) has been translated to address an international audience.The bacterial endocarditis is characterised by a constant incidence but a shift in the patient population due to the use of prosthetic heart valves and foreign materials like pacemakers and the increasing application of invasive medical procedures. This is linked to a change in the predominant infecting organisms towards staphylococci. This chapter gives recommendations for the interdisciplinary management of infective endocarditis from the diagnostic workup over prevention to therapy with a focus on antibiotic therapy.

BACKGROUND:Patients scheduled for surgery after unsuccessful MitraClip® intervention present increasingly with multiple comorbidities, and they are often referred to the heart team to suggest the most appropriate intervention. The publication of successful results of initial patient cohorts treated with the MitraClip device has resulted in recruitment of more seriously ill patients, who otherwise would have been denied catheter-based/surgical treatment. There has been increasingly reports on conventional surgery after failed mitral valve repair with the MitraClip device. However, data on such procedures remain scarce and mostly focused on individual case studies. The inevitable increase in use of MitraClip, however, will raise the number of patients in need of surgery post MitraClip, making it imperative for surgeons to understand challenges and outcome data related with surgery in this patient cohort. We present our long-term institutional experience with surgery after MitraClip intervention in highest risk patients.METHODS:Eighteen patients underwent surgery of the mitral valve at our Institution between January 2015 and June 2020. These patients developed recurrent mitral regurgitation grade more than 2° at various intervals after MitraClip. Mitral valve repair was performed where possible and gross examination Valve/MitraClip were intra-operatively documented. Implanted MitraClip devices were analyzed histopathologically to evaluate the healing process and rule out inflammation. Regular patient follow-up was performed.RESULTS:Mean patient age was 74 (±9 years) and MitraClip implantation was performed at various tertiary institutions. Sixteen out of eighteen (16/18) patients received mitral valve replacement, whereas the remaining two patients received mitral valve repair and extracorporal membrane oxygenation, respectively. Four patients died of sepsis and intractable multi organ failure in-hospital. The remaining patients were discharged alive out of hospital to different rehabilitation centers. Follow-up was complete in all patients.CONCLUSIONS:Surgery is demanding when patients require surgery for persistent or recurrent mitral regurgitation after MitraClip therapy and can be successfully implemented as a possible therapy option for selective cases as an interdisciplinary approach despite calculated high perioperative mortality risk. These patients should not be denied surgery outright.

Decellularization is a promising method for obtaining extracellular matrix scaffolds (ECM) to be used as replacement material in reconstructive procedures. The effectiveness of decellularization and the alterations to the ECM vary, depending on several factors, including the tissue source, composition and density. With an optimized decellularization process, decellularized scaffolds can preserve the spatial and temporal ECM microenvironment, which play an integral role in modulating cell migration, proliferation and differentiation. The exploration of a variety of decellularization protocols has led to mixed outcomes and comparisons between decellularization protocols could not attribute these differences to any single step in a multiple-step process. This study aimed to characterize the effects of each step of a multifactorial decellularization method on the scaffold structure and mechanical integrity of bovine pericardium. Each step of the decellularization process and the effect on the tissue was assessed using hematoxylin and eosin staining, electron microscopy, total protein, ECM protein and triglyceride quantification. The biomechanical properties were assessed using uniaxial tensile strength testing. Cell lysis occurred mainly during the detergent and alcohol steps. Collagen structural damage occurred during the detergent and alcohol steps, with no significant decreased in collagen concentration. No significant damage to elastin could be shown throughout the process, however glycosaminoglycans were significantly removed by detergent treatment. Triglycerides were removed mostly by the alcohol treatment. The strength of the pericardium decreased somewhat after each step of the protocol. It is important to characterize each decellularization protocol with regards to the decellularization efficiency and the effect on the ECM proteins structure and function to accurately evaluatein vivooutcomes.

This is the first chapter of the guideline “Calculated initial parenteral treatment of bacterial infections in adults – update 2018” in the 2 updated version. The German guideline by the Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) has been translated to address an international audience.This guideline is a revision of the recommendations published in 2010, taking into account recent substances and studies. As with previous revisions, the current situation of pathogen resistance and the results of new clinical trials are considered. The results are the present recommendations for parenteral calculated initial therapy of bacterial infections in adults. If several treatment options are mentioned, they are not always equivalent in their spectrum of microbiological activity. Therapeutic alternatives offer the opportunity to consider pathogen epidemiology, to avoid antibiotic intolerances or to escalate or de-escalate treatment in a manner suited to the situation. This article describes the different therapy options.

Patient Demographics: We report the case of a 69-year-old male patient presenting with fever, weight loss and night sweats. The neo-aortic valve was highly suspected for active infective endocarditis. Relevant History: Past medical history included cardiac surgery with pulmonary autograft replacement of the aortic valve and homograft replacement of pulmonary valve (Ross-Operation) for aortic valve stenosis 15 years earlier. Active infective endocarditis of the pulmonary autograft with severe regurgitation of the pulmonary homograft were now diagnosed. Pre-Operative Plan: Due to high suspicion of active infective endocarditis on neo-aortic and pulmonary valve, urgent surgical treatment was planned. The neo-aortic valve is implanted as full-root replacement and since calcification at the annulus was identified, and additional cardiomegaly, a 27mm Intuity bioprosthesis was scheduled, including pulmonary homograft replacement with a 27mm Freestyle bioprosthesis to reduce operative risk and avoid re-root replacement. Discussion / Course of the Case: Surgery, ICU and in-hospital-stay were uneventful and the patient was discharged 13 days post-operative with appropriate antibiotic therapy for rehabilitation. Active infective endocarditis of the pulmonary autograft in patients after Ross procedure is uncommon and requires meticulous planning prior to surgery, especially if neo-aortic valve was performed in a full-root replacement. Re-root replacement is very demanding with increased morbidity and mortality. Rapid deployment aortic valve replacement has emerged as a promising technique with good hemodynamic properties and is a viable option for patients like our case with a high surgical risk, as minimal mobilization is needed, especially as aortic valve calcification is found. Conclusion: Our case demonstrates the positive impact of optimal utilization of rapid deployment aortic valve technology combined with stentless bioprosthesis in an otherwise very high risk surgical constellation.