Case report: arrhythmic mitral valve prolapse syndrome-are risk factors underdiagnosed?

Background: Arrhythmic mitral valve prolapse syndrome (ARMV) is a recognized but underdiagnosed disease pattern. Risk factors for ARMV are established but not very well known, and the association of the structural abnormality with ventricular arrhythmias is incompletely understood. Case summary: Here, we present the case of a young man who presented at our hospital for radiofrequency catheter ablation and mitral valve surgery after two episodes of survived sudden cardiac arrest. We discuss the diagnostic and therapeutic strategies that were used. We shine light on the risk factors for ARMV and why early identification is crucial. We address the topic of primary prevention and its limitations. Finally, we discuss different treatment modalities for patients with ARMV. Discussion: More awareness for ARMV is crucial. A consensus statement on clinical management exists, but scientific gaps in prospective data for primary prevention need to be filled and there is a need for a better understanding of the pathogenesis of ARMV.

Outcomes following heart valve surgery in patients with infective endocarditis and preoperative septic cerebral embolism: insights from the CAMPAIGN study group.

OBJECTIVES: This study aimed to analyse the impact of preoperative septic cerebral embolism on early and late postoperative outcomes in patients with infective endocarditis undergoing valve surgery. METHODS: Retrospective multicentric study based on the Clinical Multicentric Project for Analysis of Infective Endocarditis in Germany (CAMPAIGN) registry comprising patients with infective endocarditis who underwent valve surgery between 1994 and 2018 at 6 German centres. Patients were divided into 2 groups for statistical comparison according to the presence or absence of preoperative septic cerebral embolism. Propensity score matching was performed for adjusted comparisons of postoperative outcomes. Primary outcomes were 30-day mortality and estimated 5-year survival. RESULTS: A total of 4917 patients were included in the analysis, 3909 (79.5%) patients without and 1008 (20.5%) patients with preoperative septic cerebral embolism. Patients with preoperative septic cerebral embolism had more baseline comorbidities. Mitral valve endocarditis (44.1% vs 33.0% P < 0.001), large vegetations >10 mm (43.1% vs 30.0%, P < 0.001), and Staphylococcus species infection (42.3% vs 21.3%, P < 0.001) were more frequent in the cerebral embolism group. Among patients with preoperative cerebral embolism, 286 (28.4%) patients had no stroke signs (silent stroke). After matching (1008 matched pairs), there was no statistically significant difference in 30-day mortality (20.1% vs 22.8%; P = 0.14) and 5-year survival (47.8% vs 49.1%; stratified log-rank P = 0.77) in patients with and without preoperative cerebral embolism, respectively. CONCLUSIONS: Preoperative septic cerebral embolism in patients with infective endocarditis requiring valve surgery does not negatively affect early or late mortality; therefore, it should not play a major role in deciding if surgery is to be performed.

Failure of Surgical Aortic Valve Prostheses: An Analysis of Heart Team Decisions and Postoperative Outcomes.

Objectives: To analyze Heart Team decisions and outcomes following failure of surgical aortic valve replacement (SAVR) prostheses. Methods: Patients undergoing re-operations following index SAVR (Redo-SAVR) and those undergoing valve-in-valve transcatheter aortic valve replacement (ViV-TAVR) following SAVR were included in this study. Patients who underwent index SAVR and/or Redo-SAVR for endocarditis were excluded. Data are presented as medians and 25th-75th percentiles, or absolute numbers and percentages. Outcomes were analyzed in accordance to the VARC-3 criteria. Results: Between 01/2015 and 03/2021, 53 patients underwent Redo-SAVR, 103 patients ViV-TAVR. Mean EuroSCORE II was 5.7% (3.5-8.5) in the Redo-SAVR group and 9.2% (5.4-13.6) in the ViV group. In the Redo-SAVR group, 12 patients received aortic root enlargement (22.6%). Length of hospital and ICU stay was longer in the Redo-SAVR group (p < 0.001; p < 0.001), PGmax and PGmean were lower in the Redo-SAVR group as compared to the ViV-TAVR group (18 mmHg (10-30) vs. 26 mmHg (19-38), p < 0.001) (9 mmHg (6-15) vs. 15 mmHg (9-21), p < 0.001). A higher rate of paravalvular leakage was seen in the ViV-TAVR group (p = 0.013). VARC-3 Early Safety were comparable between the two populations (p = 0.343). Survival at 1 year and 5 years was 82% and 36% in the ViV-TAVR cohort and 84% and 77% in the Redo-SAVR cohort. The variables were patient age (OR 1.061; [95% CI 1.020-1.104], p = 0.004), coronary heart disease (OR 2.648; [95% CI 1.160-6.048], p = 0.021), and chronic renal insufficiency (OR 2.711; [95% CI 1.160-6.048], p = 0.021) showed a significant correlation to ViV-TAVR. Conclusions: Heart Team decisions are crucial in the treatment of patients with degenerated aortic bioprostheses and lead to a low mortality in both treatment paths thanks to patient-specific therapy planning. ViV-TAVR offers a treatment for elderly or intermediate-risk profile patients with comparable short-term mortality. However, this therapy is associated with increased pressure gradients and a high prevalence of paravalvular leakage. Redo-SAVR enables the surgical treatment of concomitant cardiac pathologies and allows anticipation for later VIV-TAVR by implanting the largest possible valve prostheses.

Combination of Anti-CD40 and Anti-CD40L Antibodies as Co-Stimulation Blockade in Preclinical Cardiac Xenotransplantation.

The blockade of the CD40/CD40L immune checkpoint is considered essential for cardiac xenotransplantation. However, it is still unclear which single antibody directed against CD40 or CD40L (CD154), or which combination of antibodies, is better at preventing organ rejection. For example, the high doses of antibody administered in previous experiments might not be feasible for the treatment of humans, while thrombotic side effects were described for first-generation anti-CD40L antibodies. To address these issues, we conducted six orthotopic pig-to-baboon cardiac xenotransplantation experiments, combining a chimeric anti-CD40 antibody with an investigational long-acting PASylated anti-CD40L Fab fragment. The combination therapy effectively resulted in animal survival with a rate comparable to a previous study that utilized anti-CD40 monotherapy. Importantly, no incidence of thromboembolic events associated with the administration of the anti-CD40L PAS-Fab was observed. Two experiments failed early because of technical reasons, two were terminated deliberately after 90 days with the baboons in excellent condition and two were extended to 120 and 170 days, respectively. Unexpectedly, and despite the absence of any clinical signs, histopathology revealed fungal infections in all four recipients. This study provides, for the first time, insights into a combination therapy with anti-CD40/anti-CD40L antibodies to block this immune checkpoint.

Surgical Outcomes in Octogenarians with Heart Failure and Reduced Ejection Fraction following Isolated Coronary Artery Bypass Grafting-A Propensity Score Matched Analysis.

Background/Objectives: The demographic shift towards an aging population necessitates a reevaluation of surgical interventions like coronary artery bypass grafting (CABG) in octogenarians. This study aims to elucidate the outcomes of CABG in octogenarians with heart failure and reduced ejection fraction (HFrEF), a group traditionally considered at high risk for such procedures. Methods: Conducted across four academic hospitals in Germany from 2017 to 2023, this retrospective multicenter study assessed 100 patients (50 octogenarians ≥80 years and 50 non-octogenarians <80 years) with HFrEF undergoing isolated CABG. Through propensity score matching, the study aimed to compare the incidence of major adverse cardiac and cerebrovascular events (MACCEs), as well as other clinical endpoints, between the two groups. Statistical analyses included chi-square, ANOVA, Mann-Whitney U test, Cox regression, and logistic regression, aiming to identify significant differences in outcomes. Results: The study revealed no significant difference in the combined incidence of MACCEs between octogenarians and non-octogenarians (OR: 0.790, 95% CI: 0.174-3.576, p = 0.759). Mortality rates were similar across groups (7% each, p = 1.000), as were occurrences of postoperative myocardial infarction (2% each, p = 1.000) and stroke (3% total). Secondary outcomes like delirium (17% total, no significant age group difference, p = 0.755), acute kidney injury (18% total, p = 0.664), and the need for dialysis (14% total, p = 1.000) also showed no differences between age groups. Interestingly, non-octogenarians required more packed red blood cells during their stay (p = 0.008), while other postoperative care metrics, such as hospital and ICU length of stay and ventilation hours, were comparable across groups. Conclusion: This multicenter study highlights that CABG is a viable and safe surgical option for octogenarians with HFrEF, challenging prior assumptions about the elevated risks associated with performing this procedure in older patients. The absence of significant differences in the incidence of MACCEs and other postoperative complications across age groups emphasizes the importance of careful patient selection and perioperative management. These findings advocate for a more inclusive approach to surgical treatment for octogenarians with HFrEF, suggesting that age alone should not be a determinant for CABG eligibility. This study contributes critical insights into optimizing care for a high-risk demographic, indicating a need for tailored guidelines that accommodate the aging population with complex cardiac conditions.

Transcatheter Repair versus Mitral-Valve Surgery for Secondary Mitral Regurgitation.

BACKGROUND: Current treatment recommendations for patients with heart failure and secondary mitral regurgitation include transcatheter edge-to-edge repair and mitral-valve surgery. Data from randomized trials comparing these therapies are lacking in this patient population. METHODS: In this noninferiority trial conducted in Germany, patients with heart failure and secondary mitral regurgitation who continued to have symptoms despite guideline-directed medical therapy were randomly assigned, in a 1:1 ratio, to undergo either transcatheter edge-to-edge repair (intervention group) or surgical mitral-valve repair or replacement (surgery group). The primary efficacy end point was a composite of death, hospitalization for heart failure, mitral-valve reintervention, implantation of an assist device, or stroke within 1 year after the procedure. The primary safety end point was a composite of major adverse events within 30 days after the procedure. RESULTS: A total of 210 patients underwent randomization. The mean (±SD) age of the patients was 70.5±7.9 years, 39.9% were women, and the mean left ventricular ejection fraction was 43.0±11.7%. Within 1 year, at least one of the components of the primary efficacy end point occurred in 16 of the 96 patients with available data (16.7%) in the intervention group and in 20 of the 89 with available data (22.5%) in the surgery group (estimated mean difference, -6 percentage points; 95% confidence interval [CI], -17 to 6; P<0.001 for noninferiority). A primary safety end-point event occurred in 15 of the 101 patients with available data (14.9%) in the intervention group and in 51 of the 93 patients with available data (54.8%) in the surgery group (estimated mean difference, -40 percentage points; 95% CI, -51 to -27; P<0.001). CONCLUSIONS: Among patients with heart failure and secondary mitral regurgitation, transcatheter edge-to-edge repair was noninferior to mitral-valve surgery with respect to a composite of death, rehospitalization for heart failure, stroke, reintervention, or implantation of an assist device in the left ventricle at 1 year. (Funded by Abbott Vascular; MATTERHORN ClinicalTrials.gov number, NCT02371512.).

Association between caseload volume and outcomes in left ventricular assist device implantations - a EUROMACS analysis.

AIMS: This EUROMACS study was conducted with the primary aim of investigating the association between a centre's annual caseload and postoperative outcomes among patients undergoing left ventricular assist device (LVAD) implantation. METHODS AND RESULTS: A total of 4802 patients identified between 2011 and 2020 from 35 participating centres were dichotomized based on the annual caseload of the treating centre at the time of device implant (≤30 vs. >30 LVAD implantations/year). The primary endpoint was 1-year survival. Secondary outcomes included overall survival analysis, device-related adverse events and readmissions. Cumulative follow-up was 10 003 patient-years, with a median follow-up of 1.54 years (interquartile range 0.52-3.15). Patients from higher volume centres more frequently presented in INTERMACS levels 1 and 2, suffered from right heart dysfunction and needed inotropic support. No difference was observed in adjusted 1-year survival. Adjusted overall survival probability was lower in higher volume centres (p = 0.002). In the subgroup analysis of HeartMate 3 devices only, higher volume centres were associated with decreased odds of 1-year survival (adjusted odds ratio 0.43, 95% confidence interval 0.20-0.97, p = 0.041). Similar findings were observed in the cumulative (i.e. learning curve) caseload analyses. CONCLUSION: In patients undergoing LVAD implantation, centre volume was not associated with 1-year survival, but was related to device-related adverse events. Patient profiles differed with respect to centre size. These findings underscore the necessity for ongoing quality improvement initiatives in all centres, regardless of their annual caseload. Efforts are needed to standardize patient selection and preconditioning to further improve patient outcome.

Serum concentrations of levosimendan and its metabolites OR-1855 and OR-1896 in cardiac surgery patients with cardiopulmonary bypass.

Background: The inotropic drug levosimendan is often used as an individualized therapeutic approach perioperatively in cardiac surgery patients with cardiopulmonary bypass (CPB). Data regarding serum concentrations of levosimendan and its metabolites within this context is lacking. Methods: In this retrospective descriptive proof-of-concept study, total serum concentrations (TSC) and unbound fractions (UF) of levosimendan and its metabolites OR-1896 and OR-1855 in cardiac surgery patients with CPB were measured using LC-ESI-MS/MS. Simulation of expected levosimendan TSC was performed using Pharkin 4.0. Serum NT-proBNP was assessed with ELISA. Results: After levosimendan infusion (1.25 mg or 2.5 mg, respectively) after anaesthesia induction, a median TSC of 1.9 ng/ml and 10.4 ng/ml was determined in samples taken directly after surgery (T1). Median TSC of 7.6 ng/ml and 22.0 ng/ml, respectively, were simulated at T1. Whereas 1.1 ng/ml and 1.6 ng/ml TSC of OR-1896, respectively, was quantified the day after surgery (T2), TSC of the intermediate metabolite OR-1855 was mostly below the lower limit of quantification (LLOQ). The UF was 0.5% and 1.1% for levosimendan and 64.1% and 52.1% for OR-1896, respectively, with over half the samples being below LLOQ. NT-proBNP concentrations before surgery and T2 did not differ. Discussion: The low TSC, UF and unchanged NT-proBNP levels in combination with high variation of serum levels between patients suggest a need for optimized dosing regimen of levosimendan combined with therapeutic drug monitoring for such an individualized approach. In addition, the differences between the measured and estimated concentrations may suggest a possible influence of CPB on levosimendan serum concentrations.

Aortic valved homograft degeneration: surgical or transcatheter approach for repeat aortic valve replacement?

OBJECTIVES: Aortic valved allografts (homografts) have been used alternatively to mechanical or biological valve prostheses in expectation of better durability; however, homograft valves do degenerate, and redo procedures have proven challenging due to heavy wall calcification. The aim of the study was to compare the outcome of open surgical (SAVR) and transcatheter aortic valve replacement (TAVR) in degenerated homografts. METHODS: Between 1993 and 2022, 81 patients underwent repeat aortic valve procedures having previously received an aortic homograft. The redo had become necessary due to regurgitation in 85% and stenosis in 15%. Sixty-five percent underwent open surgery, 35% TAVR. RESULTS: Isolated SAVR was possible in 79%, and root procedures were necessary in 21%. TAVR was performed in 79% via transfemoral and 21% via transapical access. Median prosthetic valve size was 23 (22.3-23.2) mm in the SAVR and 26 (25.2-26.9) in the TAVR group. Thirty-day mortality was 0% in the TAVR and 7% in the SAVR group (P = n.s.). TAVR showed a significantly better outcome concerning prolonged ventilation (0 vs 21%, P = 0.013) as well as ICU (1 vs 2 days; P < 0.001) and in-hospital stay (10.5 vs 13 days; P = 0.028). Five-year survival was statistically comparable between groups, and no severe leakage was observed. CONCLUSIONS: SAVR following structural homograft degeneration shows acceptable results, but the perioperative risk remains substantial and poorly predictable. TAVR presents a reasonable and more easily accessible alternative and is associated with good short- and mid-term results. In the absence of relevant contraindications, TAVR is presently the preferred treatment option for these patients at our center.

Sex-related differences in patients with infective endocarditis requiring cardiac surgery: insights from the CAMPAIGN Study Group.

OBJECTIVES: Sex-related differences play a role in cardiovascular disease-related outcomes. There is, however, a knowledge gap regarding sex-specific differences in patients with infective endocarditis (IE)-requiring surgical treatment. This study aims to analyse sex-related differences in the clinical presentation, treatment and clinical outcomes of patients with IE-requiring surgical treatment from the multicentric Germany-wide CAMPAIGN registry. METHODS: Patients with IE who underwent cardiac surgery between 1994 and 2018 at six German centres were retrospectively analysed. Outcomes were compared based on patients' sex. Primary outcomes were 30-day mortality and mid-term survival. RESULTS: A total of 4917 patients were included in the analysis (1364 female [27.7%] and 3553 male [72.3%]). Female patients presented with more comorbidities and higher surgical risk (EuroScore II 12.0% vs 10.0%, P < 0.001). The early postoperative course of female patients was characterized by longer ventilation times (20.0 h vs 16.0 h; P = 0.004), longer intensive care unit stay (4.0 days vs 3.0 days; P < 0.001), and more frequent new-onset dialysis (265 [20.3%] vs 549 [16.3%]; P = 0.001). The 30-day mortality was 13.8% and 15.5% in female and male patients, respectively (P = 0.06). The estimated mid-term survival was significantly higher amongst male patients (56.1% vs 45.4%; Log-rank P < 0.001). Female sex was an independent predictor of mid-term mortality (HR 1.2 [95% CI 1.0-1.4], P = 0.01). CONCLUSIONS: Male patients more frequently undergo cardiac surgery for IE. However, female patients have a higher surgical risk profile and subsequently an increased early postoperative morbidity, but with similar 30-day mortality compared with male patients. The estimated mid-term survival is lower amongst female patients.

Infective endocarditis and spondylodiscitis-impact of sequence of surgical therapy on survival and recurrence rate.

OBJECTIVES: To date, there are no standardized treatment algorithms or recommendations for patients with infective endocarditis (IE) and concomitant spondylodiscitis (SD). Therefore, our aim was to analyse whether the sequence of surgical treatment of IE and SD has an impact on postoperative outcome and to identify risk factors for survival and postoperative recurrence. METHODS: Patients with IE underwent surgery in 4 German university hospitals between 1994 and 2022. Univariable and multivariable analyses were performed to identify possible predictors of 30-day/1-year mortality and recurrence of IE and/or SD. RESULTS: From the total IE cohort (n = 3991), 150 patients (4.4%) had concomitant SD. Primary surgery for IE was performed in 76.6%, and primary surgery for SD in 23.3%. The median age was 70.0 (64.0-75.6) years and patients were mostly male (79.5%). The most common pathogens detected were enterococci and Staphylococcus aureus followed by streptococci, and coagulase-negative Staphylococci. If SD was operated on first, 30-day mortality was significantly higher than if IE was operated on 1st (25.7% vs 11.4%; P = 0.037) and we observed a tendency for a higher 1-year mortality. If IE was treated 1st, we observed a higher recurrence rate within 1 year (12.2% vs 0%; P = 0.023). Multivariable analysis showed that primary surgery for SD was an independent predictor of 30-day mortality. CONCLUSIONS: Primary surgical treatment for SD was an independent risk factor for 30-day mortality. When IE was treated surgically 1st, the recurrence rate of IE and/or SD was higher.

An Approach to Controlling Inflammation and Coagulation in Pig-to-Baboon Cardiac Xenotransplantation.

INTRODUCTION: Inflammatory responses and coagulation disorders are a relevant challenge for successful cardiac xenotransplantation on its way to the clinic. To cope with this, an effective and clinically practicable anti-inflammatory and anti-coagulatory regimen is needed. The inflammatory and coagulatory response can be reduced by genetic engineering of the organ-source pigs. Furthermore, there are several therapeutic strategies to prevent or reduce inflammatory responses and coagulation disorders following xenotransplantation. However, it is still unclear, which combination of drugs should be used in the clinical setting. To elucidate this, we present data from pig-to-baboon orthotopic cardiac xenotransplantation experiments using a combination of several anti-inflammatory drugs. METHODS: Genetically modified piglets (GGTA1-KO, hCD46/hTBM transgenic) were used for orthotopic cardiac xenotransplantation into captive-bred baboons (n = 14). All animals received an anti-inflammatory drug therapy including a C1 esterase inhibitor, an IL-6 receptor antagonist, a TNF-α inhibitor, and an IL-1 receptor antagonist. As an additive medication, acetylsalicylic acid and unfractionated heparin were administered. The immunosuppressive regimen was based on CD40/CD40L co-stimulation blockade. During the experiments, leukocyte counts, levels of C-reactive protein (CRP) as well as systemic cytokine and chemokine levels and coagulation parameters were assessed at multiple timepoints. Four animals were excluded from further data analyses due to porcine cytomegalovirus/porcine roseolovirus (PCMV/PRV) infections (n = 2) or technical failures (n = 2). RESULTS: Leukocyte counts showed a relevant perioperative decrease, CRP levels an increase. In the postoperative period, leukocyte counts remained consistently within normal ranges, CRP levels showed three further peaks after about 35, 50, and 80 postoperative days. Analyses of cytokines and chemokines revealed different patterns. Some cytokines, like IL-8, increased about 2-fold in the perioperative period, but then decreased to levels comparable to the preoperative values or even lower. Other cytokines, such as IL-12/IL-23, decreased in the perioperative period and stayed at these levels. Besides perioperative decreases, there were no relevant alterations observed in coagulation parameters. In summary, all parameters showed an unremarkable course with regard to inflammatory responses and coagulation disorders following cardiac xenotransplantation and thus showed the effectiveness of our approach. CONCLUSION: Our preclinical experience with the anti-inflammatory drug therapy proved that controlling of inflammation and coagulation disorders in xenotransplantation is possible and well-practicable under the condition that transmission of pathogens, especially of PCMV/PRV to the recipient is prevented because PCMV/PRV also induces inflammation and coagulation disorders. Our anti-inflammatory regimen should also be applicable and effective in the clinical setting of cardiac xenotransplantation.

Heparin-Induced Thrombocytopenia in Patients Suffering Cardiogenic Shock.

OBJECTIVES: Cardiogenic shock (CS) is associated with high mortality. Patients treated for CS mostly require heparin therapy, which may be associated with complications such as heparin-induced thrombocytopenia (HIT). HIT represents a serious condition associated with platelet decline and increased hypercoagulability and remains a poorly researched field in intensive care medicine. Primary purpose of this study was to: 1) determine HIT prevalence in CS, 2) assess the performance of common diagnostic tests for the workup of HIT, and 3) compare outcomes in CS patients with excluded and confirmed HIT. DESIGN: Retrospective dual-center study including adult patients 18 years old or older with diagnosed CS and suspected HIT from January 2010 to November 2022. SETTING: Cardiac ICU at the Ludwig-Maximilians University hospital in Munich and the university hospital of Bonn. PATIENTS AND INTERVENTIONS: In this retrospective analysis, adult patients with diagnosed CS and suspected HIT were included. Differences in baseline characteristics, mortality, neurologic and safety outcomes between patients with excluded and confirmed HIT were evaluated. MEASUREMENTS AND MAIN RESULTS: In cases of suspected HIT, positive screening antibodies were detected in 159 of 2808 patients (5.7%). HIT was confirmed via positive functional assay in 57 of 2808 patients, corresponding to a prevalence rate of 2.0%. The positive predictive value for anti-platelet factor 4/heparin screening antibodies was 35.8%. Total in-hospital mortality (58.8% vs. 57.9%; p > 0.999), 1-month mortality (47.1% vs. 43.9%; p = 0.781), and 12-month mortality (58.8% vs. 59.6%; p > 0.999) were similar between patients with excluded and confirmed HIT, respectively. Furthermore, no significant difference in neurologic outcome among survivors was found between groups (Cerebral Performance Category [CPC] score 1: 8.8% vs. 8.8%; p > 0.999 and CPC 2: 7.8% vs. 12.3%; p = 0.485). CONCLUSIONS: HIT was a rare complication in CS patients treated with unfractionated heparin and was not associated with increased mortality. Also, HIT confirmation was not associated with worse neurologic outcome in survivors. Future studies should aim at developing more precise, standardized, and cost-effective strategies to diagnose HIT and prevent complications.

Hemodynamics in pig-to-baboon heterotopic thoracic cardiac xenotransplantation: Recovery from perioperative cardiac xenograft dysfunction and impairment by cardiac overgrowth.

INTRODUCTION: Orthotopic cardiac xenotransplantation has seen notable improvement, leading to the first compassionate use in 2022. However, it remains challenging to define the clinical application of cardiac xenotransplantation, including the back-up strategy in case of xenograft failure. In this regard, the heterotopic thoracic technique could be an alternative to the orthotopic procedure. We present hemodynamic data of heterotopic thoracic pig-to-baboon transplantation experiments, focusing on perioperative xenograft dysfunction and xenograft overgrowth. METHODS: We used 17 genetically modified piglets as donors for heterotopic thoracic xenogeneic cardiac transplantation into captive-bred baboons. In all animals, pressure probes were implanted in the graft's left ventricle and the recipient's ascending aorta and hemodynamic data (graft pressure, aortic pressure and recipient's heart rate) were recorded continuously. RESULTS: Aortic pressures and heart rates of the recipients' hearts were postoperatively stable in all experiments. After reperfusion, three grafts presented with low left ventricular pressure indicating perioperative cardiac dysfunction (PCXD). These animals recovered from PCXD within 48 h under support of the recipient's heart and there was no difference in survival compared to the other 14 ones. After 48 h, graft pressure increased up to 200 mmHg in all 17 animals with two different time-patterns. This led to a progressive gradient between graft and aortic pressure. With increasing gradient, the grafts stopped contributing to cardiac output. Grafts showed a marked weight increase from implantation to explantation. CONCLUSION: The heterotopic thoracic cardiac xenotransplantation technique is a possible method to overcome PCXD in early clinical trials and an experimental tool to get a better understanding of PCXD. The peculiar hemodynamic situation of increasing graft pressure but missing graft's output indicates outflow tract obstruction due to cardiac overgrowth. The heterotopic thoracic technique should be successful when using current strategies of immunosuppression, organ preservation and donor pigs with smaller body and organ size.

The Endothelial Glycocalyx in Pig-to-Baboon Cardiac Xenotransplantation-First Insights.

Cardiac xenotransplantation has seen remarkable success in recent years and is emerging as the most promising alternative to human cardiac allotransplantation. Despite these achievements, acute vascular rejection still presents a challenge for long-term xenograft acceptance and new insights into innate and adaptive immune responses as well as detailed characterizations of signaling pathways are necessary. In allotransplantation, endothelial cells and their sugar-rich surface-the endothelial glycocalyx-are known to influence organ rejection. In xenotransplantation, however, only in vitro data exist on the role of the endothelial glycocalyx so far. Thus, in the current study, we analyzed the changes of the endothelial glycocalyx components hyaluronan, heparan sulfate and syndecan-1 after pig-to-baboon cardiac xenotransplantations in the perioperative (n = 4) and postoperative (n = 5) periods. These analyses provide first insights into changes of the endothelial glycocalyx after pig-to-baboon cardiac xenotransplantation and show that damage to the endothelial glycocalyx seems to be comparable or even less pronounced than in similar human settings when current strategies of cardiac xenotransplantation are applied. At the same time, data from the experiments where current strategies, like non-ischemic preservation, growth inhibition or porcine cytomegalovirus (a porcine roseolovirus (PCMV/PRV)) elimination could not be applied indicate that damage of the endothelial glycocalyx also plays an important role in cardiac xenotransplantation.

Influence of donor age and donor-recipient age difference on intimal hyperplasia in pediatric patients with young and adult donors vs. adult patients after heart transplantation.

AIM: Optimal selection and allocation of donor hearts is a relevant aspect in transplantation medicine. Donor age and cardiac allograft vasculopathy (CAV) affect post-transplant mortality. To what extent donor age impacts intimal hyperplasia (CAVIH) in pediatric and adult patients after heart transplantation (HTx) is understudied. METHODS: In a cohort of 98 HTx patients, 58 pediatric (24.1% with adult donors) and 40 adult patients, we assessed the effect of donor age and donor-recipient age difference (D-R) on the continuous parameter of maximal intima thickness (mIT) in optical coherence tomography. We evaluated their predictive value regarding higher mIT and the prevalence of CAVIH, defined as mIT > 0.3 mm, and compared it to established CAV risk factors. RESULTS: In the overall population, donor age correlated with mIT (p < 0.001), while in the pediatric subpopulation, both donor age and D-R correlated with mIT (p < 0.001 and p = 0.002, respectively). In the overall population, donor age was a main predictor of higher mIT and CAVIH (p = 0.001 and p = 0.01, respectively) in addition to post-transplant interval, arterial hypertension, and dyslipidemia. In the pediatric patients, dyslipidemia remained a main predictor of both higher mIT and CAVIH (p = 0.004 and p = 0.040, respectively), while donor age and D-R were not. CONCLUSION: While there was an effect of the non-modifiable parameter of donor age regarding maximal intimal thickness, a stronger association was seen between the modifiable risk factor dyslipidemia and higher maximal intimal thickness and CAVIH in both the overall population and the pediatric subpopulation.

[Xenotransplantation of solid organs]. / Xenotransplantation von Organen.

Transplantation of genetically modified porcine hearts and kidneys could become a solution to the persistent shortage of human organ donors. Progress has been made in genetic engineering of donor pigs, preservation techniques after organ harvesting and immunosuppression using co-stimulation blockade with anti-CD40/CD40L monoclonal antibodies. Progress has also been made in in the development of methods that detect pathogenic porcine viruses and prevent their transmission to the recipient. As normal land breed pig organs continue to grow in the recipient to their original size, different pig breeds (such as Auckland Island pigs) are now used which reach a final size suitable for humans. Alternatively, a knock-out of the growth hormone receptor gene has been established, e.g., in the 10GM genetically modified pigs from Revivicor/United Therapeutics, USA. The first clinical pilot studies including patients suffering from terminal heart failure are expected to start in Germany in about 2 years.

"Loss of landing zone"-Stabilizing endovascular treatment solutions in the aortic arch after thoracic endovascular aortic repair.

Addressing proximal complications that arise after endovascular aortic repair for type B aortic dissection, such as type Ia endoleaks, "bird-beaking" of the thoracic endovascular aortic repair (TEVAR) stent, retrograde type A dissection, and postdissection aneurysms, bears considerable complexities. We present a novel and safe method for open arch repair that can ensure a secure and efficient approach for TEVAR complications. The key element of the operative technique is approximating the grafted stent portion to the aortic wall and the arch prosthesis. The technique has successfully been implemented in 11 patients, who received secondary open arch repair from 2019 to 2022 after TEVAR for type B dissection. Our objective is not only to introduce this reliable concept but also to provide a comprehensive demonstration of its advantages and disadvantages compared with currently used open treatment methods and discuss patient outcomes after secondary open arch repair.

Transcatheter heart valve explant with infective endocarditis-associated prosthesis failure and outcomes: the EXPLANT-TAVR international registry.

BACKGROUND AND AIMS: Surgical explantation of transcatheter heart valves (THVs) is rapidly increasing, but there are limited data on patients with THV-associated infective endocarditis (IE). This study aims to assess the outcomes of patients undergoing THV explant for IE. METHODS: All patients who underwent THV explant between 2011 and 2022 from 44 sites in the EXPLANT-TAVR registry were identified. Patients with IE as the reason for THV explant were compared to those with other mechanisms of bioprosthetic valve dysfunction (BVD). RESULTS: A total of 372 patients from the EXPLANT-TAVR registry were included. Among them, 184 (49.5%) patients underwent THV explant due to IE and 188 (50.5%) patients due to BVD. At the index transcatheter aortic valve replacement, patients undergoing THV explant for IE were older (74.3 ± 8.6 vs. 71 ± 10.6 years) and had a lower Society of Thoracic Surgeons risk score [2.6% (1.8-5.0) vs. 3.3% (2.1-5.6), P = .029] compared to patients with BVD. Compared to BVD, IE patients had longer intensive care unit and hospital stays (P < .05) and higher stroke rates at 30 days (8.6% vs. 2.9%, P = .032) and 1 year (16.2% vs. 5.2%, P = .010). Adjusted in-hospital, 30-day, and 1-year mortality was 12.1%, 16.1%, and 33.8%, respectively, for the entire cohort, with no significant differences between groups. Although mortality was numerically higher in IE patients 3 years postsurgery (29.6% for BVD vs. 43.9% for IE), Kaplan-Meier analysis showed no significant differences between groups (P = .16). CONCLUSIONS: In the EXPLANT-TAVR registry, patients undergoing THV explant for IE had higher 30-day and 1-year stroke rates and longer intensive care unit and hospital stays. Moreover, patients undergoing THV explant for IE had a higher 3-year mortality rate, which did not reach statistical significance given the relatively small sample size of this unique cohort and the reduced number of events.