Minimally invasive direct coronary artery bypass and percutaneous coronary intervention followed by transcatheter aortic valve implantation: A promising concept in high-risk octogenarians.

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 New York 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.

Sarcomeric network analysis of ex vivo cultivated human atrial appendage tissue using super-resolution microscopy.

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.

Impact of Three Different Processing Techniques on the Strength and Structure of Juvenile Ovine Pulmonary Homografts.

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.

Introduction of the Rapid Deployment Aortic Valve System Use in Elderly Patients With Endocarditis.

Introduction: The 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 Methods: Since 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. Results: Three 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%). Conclusion: Rapid-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.

Surgery for Valvular and Nonvalvular Papillary Fibroelastomas.

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.

Hybrid approach for percutaneous mitral valve repair (MitraClip®) followed by minimally invasive direct coronary artery bypass (MIDCAB) in a patient with a high risk constellation.

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.

Papillary Fibroelastoma in Differential Diagnosis of Left Atrial Appendage Masses.

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.

Aortic valve and coronary artery bypass surgery in a patient with factor VII deficiency.

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.

Surgical revision after percutaneous mitral valve repair by edge-to-edge device in high-risk patients.

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.

Calculated initial parenteral treatment of bacterial infections: Bacterial endocarditis.

This is the twelfth chapter of the guideline "Calculated initial parenteral treatment of bacterial infections in adults - update 2018" in the 2nd 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.

Calculated parenteral initial treatment of bacterial infections: Introduction and antibiotics.

This is the first chapter of the guideline "Calculated initial parenteral treatment of bacterial infections in adults - update 2018" in the 2nd 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.

Synergy in a detergent combination results in superior decellularized bovine pericardial extracellular matrix scaffolds.

Decellularization involves removal of cellular material from tissue which results in a scaffold material consisting of only the extra cellular matrix (ECM). The effect of each individual decellularizing detergent on the final ECM scaffold and how that may differ from the combined use of these detergents is currently a gap in decellularization methodologies. This study evaluates the hypothesis that a synergistic effect exists when commonly used decellularization detergents are combined. This was evaluated with regard to decellularization efficiency, tissue strength, and collagen structure. Bovine pericardium was decellularized using a combination of 0.5% sodium dodecyl sulfate (SDS), 1% sodium deoxycholate (SDC) and 1% TritonX-100, and compared to the use of each detergent individually. The combined detergent decellularization protocol showed effective decellularization (p = .004), with minimal effects on tissue strength (p = .21) and structure (p = .21). Use of detergents individually, resulted in detrimental effects on tissue structure and integrity or ineffective decellularization. This study shows a synergistic relationship between SDS, SDC and TritonX-100 when combined at specific concentrations. The use of detergents in combination instead of individually appears to be superior, as it results in less ECM damage and improved decellularization effectivity.

Tissue Engineered Small Vessel Conduits - The Anti-Thrombotic Effect of Re-Endothelialization of Decellularized Baboon Arteries: A Preliminary Experimental Study.

BACKGROUND The use of decellularized biological scaffolds for the reconstruction of small-diameter vascular grafts remains a challenge in tissue engineering. Thrombogenicity is an important cause of obstruction in these vessels due to decellularization. Seeding of the decellularized vascular constructs with endothelial cells is therefore a prerequisite for the prevention of thrombosis. The aim of this study was to seed decellularized baboon arteries with endothelial cells and to compare the thrombogenicity to that of decellularized arteries after circulation of blood. MATERIAL AND METHODS Carotid, radial, and femoral arteries (12 arteries in total) were harvested from 2 Papio ursinus baboons. Ten arteries were decellularized. Normal morphology was confirmed in the control vessels. The effect of re-endothelialization was studied in the vessel scaffolds using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Decellularization resulted in vessel scaffolds with well-preserved extracellular matrix and intact basal membranes. Six of the decellularized vessel scaffolds were seeded with viable human umbilical vein endothelial cells (HUVEC). Luminal endothelialization was established after 7 days in a bioreactor and SEM confirmed confluency. Two control, 4 decellularized, and 6 decellularized re-endothelialized vessel scaffolds were studied in an in vitro flow chamber using baboon blood. RESULTS The decellularized arteries showed an absence of endothelial lining, and an intact basement membrane. The seeding process produced a complete endothelial layer on the surfaces of the arteries. After perfusion with whole blood, no thrombi were formed in the control arteries and re-endothelialized vessels. Widespread platelet activation and adhesion occurred in the decellularized vessels despite a relatively intact basal membrane. CONCLUSIONS This study supports the development of re-endothelialized tissue engineered small-vessel conduits.

Surgery for Infective Endocarditis: Outcomes and Predictors of Mortality in 360 Consecutive Patients.

BACKGROUND A retrospective analysis was conducted of the early and long-term outcomes after surgery for infective endocarditis (IE). MATERIAL AND METHODS We included 360 patients with IE operated upon between 1993 and 2012. The primary endpoint was overall cumulative postoperative survival at 30 days. Secondary endpoints were early postoperative outcomes and complication rates. Factors associated with 30-day mortality were analyzed. RESULTS Mean age was 58.7±14.7 years and 26.9% (n=97) were female. The mean follow-up was 4.41±4.53 years. Postoperative survival was 81.7% at 30 days, 69.4% at 1 year, 63.3% at 5 years, and 63.3% at 10 years. Non-survivors were significantly older (p=0.014), with higher NYHA Class (p=0.002), had higher rates of preoperative diabetes mellitus (p=0.005), renal failure (p=0.001), and hepatic disease (p=0.002). Furthermore, non-survivors had higher baseline alanine aminotransferase (ALT, p=0.048), aspartate transaminase (AST, p=0.027), bilirubin (p=0.013), white cell count (WCC, p=0.034), and CRP (p=0.049). Factors associated with 30-day mortality were longer duration of surgery, CPB, and aortic cross-clamping times (p<0.001, p<0.001, and p=0.003, respectively), as well as higher RBC, FFP, and platelet transfusion requirements (p<0.001, p=0.005, and p<0.001, respectively). Multivariate logistic regression analysis revealed liver cirrhosis (OR 4.583, 95-CI: 1.096-19.170, p=0.037) and longer CPB time (OR 1.025, 95-CI 1.008-1.042, p=0.004) as independent predictors of 30-day mortality. CONCLUSIONS Surgical treatment of IE shows satisfactory early, midterm, and long-term results. Multivariate logistic regression analysis revealed cirrhosis and longer CPB time as independent predictors of 30-day mortality.

Are Sutureless Aortic Valves Suitable for Severe High-Risk Patients Suffering from Active Infective Aortic Valve Endocarditis?

BACKGROUND Sutureless aortic valves were introduced to facilitate minimally invasive aortic valve surgery. Since sutureless aortic valves are a feasible procedure, we evaluated if any benefits could be identified in severe high-risk patients with active infective endocarditis of the aortic valve. MATERIAL AND METHODS Between April 2014 and April 2015, a total of 42 patients received a sutureless Perceval® aortic valve (Sorin Biomedica Cardio Srl, Saluggia, Italy) for different indications. Nine of these patients (median age 71 years, range 47-83 years) suffered from active infective endocarditis, including four patients with prosthetic aortic valve endocarditis. Five patients underwent prior cardiac surgery, including transcatheter aortic valve implantation (TAVI). The median EuroSCORE II was 29.5% (range 16.8-87.7%). Post-operatively, data regarding mortality, operative results, and early operative morbidity were collected. RESULTS There were no cases of 30-day mortality. Four patients needed abscess closure with pericardium. Three patients underwent left atrial appendix closure: one left ventricular thrombectomy, one bypass grafting, and one arch replacement. Median aortic cross-clamp and cardiopulmonary bypass time was 35 minutes (range 26-88 minutes) and 52 minutes (range 40-133 minutes), respectively. The median intubation time was 14 hours (range 1-9 hours). In these high-risk patients, no postoperative morbidity was found except for one re-intubation due to extensive delirium and one re-exploration. No pacemaker implantation was needed. Echocardiographic evaluation showed no central or para-valvular regurgitation, and a median discharge mean gradient of 5.5 mm Hg (range 2.5-10.0 mm Hg). CONCLUSIONS Sutureless aortic valve replacement in very high-risk patients suffering from active infection endocarditis seems to be an option with limited morbidity and appropriate echocardiographic results, however, further studies are needed.

Impedimetric Analysis of the Effect of Decellularized Porcine Heart Scaffold on Human Fibrosarcoma, Endothelial, and Cardiomyocyte Cell Lines.

BACKGROUND Experiments on porcine heart scaffold represent significant assays in development of immunoneutral materials for cardiac surgery. Characterization of cell-cell and cell-scaffold interactions is essential to understand the homing process of cardiac cells into the scaffolds. MATERIAL AND METHODS In the present study, the highly sensitive and real-time impedimetric technique of xCELLigence SP was used to monitor cell adhesion, which is the key process of recellularization in heart scaffolds. Our objectives were: (i) to characterize the effect of decellularized porcine heart scaffold on cell adhesion of human cardiovascular cells potentially used in the recellularization process; and (ii) to investigate cell-extracellular matrix element interactions for building artificial multi-layer systems, applied as cellular models of recellularization experiments. Human fibrosarcoma, endothelial, and cardiomyocyte cells were investigated and the effect of decellularized porcine heart scaffold (HS) and fibronectin on cell adhesion was examined. Adhesion was quantified as slope of curves. RESULTS Heart scaffold had neutral effect on cardiomyocytes as well as on endothelial cells. Adhesion of cardiomyocytes was increased by fibronectin (1.480±0.021) compared to control (0.745±0.029). The combination of fibronectin and HS induced stronger adhesion of cardiomyocytes (2.407±0.634) than fibronectin alone. Endothelial and fibrosarcoma cells showed similarly strong adhesion profiles with marked enhancer effect by fibronectin. CONCLUSIONS Decellularized porcine HS does not inhibit adhesion of human cardiovascular cells at the cell biological level, while fibronectin has strong cell adhesion-inducer effect, as well as an enhancer effect on activity of HS. Consequently, decellularized porcine hearts could be used as scaffolds for recellularization with cardiomyocytes and endothelial cells with fibronectin acting as a regulator, leading to construction of working bioartificial hearts.

Prediction of New-Onset and Recurrent Atrial Fibrillation by Complete Blood Count Tests: A Comprehensive Systematic Review with Meta-Analysis.

BACKGROUND Atrial fibrillation (AF) is one of the most critical and frequent arrhythmias precipitating morbidities and mortalities. The complete blood count (CBC) test is an important blood test in clinical practice and is routinely used in the workup of cardiovascular diseases. This systematic review with meta-analysis aimed to determine the strength of evidence for evaluating the association of hematological parameters in the CBC test with new-onset and recurrent AF. MATERIAL AND METHODS We conducted a meta-analysis of observational studies evaluating hematologic parameters in patients with new-onset AF and recurrent AF. A comprehensive subgroup analysis was performed to explore potential sources of heterogeneity. RESULTS The literature search of all major databases retrieved 2150 studies. After screening, 70 studies were analyzed in the meta-analysis on new-onset AF and 23 studies on recurrent AF. Pooled analysis on new-onset AF showed platelet count (PC) (weighted mean difference (WMD)=WMD of -26.39×10^9/L and p<0.001), mean platelet volume (MPV) (WMD=0.42 FL and p<0.001), white blood cell (WBC) (WMD=-0.005×10^9/L and p=0.83), neutrophil to lymphocyte ratio (NLR) (WMD=0.89 and p<0.001), and red blood cell distribution width (RDW) (WMD=0.61% and p<0.001) as associated factors. Pooled analysis on recurrent AF revealed PC (WMD=-2.71×109/L and p=0.59), WBC (WMD=0.20×10^9/L (95% CI: 0.08 to 0.32; p=0.002), NLR (WMD=0.37 and p<0.001), and RDW (WMD=0.28% and p<0.001). CONCLUSIONS Hematological parameters have significant ability to predict occurrence and recurrence of AF. Therefore, emphasizing the potential predictive role of hematological parameters for new-onset and recurrent AF, we recommend adding the CBC test to the diagnostic modalities of AF in clinical practice.