Paediatric aortic valve replacement using decellularized allografts: a multicentre update following 143 implantations and five-year mean follow-up.

OBJECTIVES: Decellularized aortic homografts (DAH) were introduced in 2008 as a further option for paediatric aortic valve replacement (AVR). METHODS: Prospective, multicentre follow-up of all paediatric patients receiving DAH for AVR in 8 European centres. RESULTS: A total of 143 DAH were implanted between February 2008 and February 2023 in 137 children (106 male, 74%) with a median age of 10.8 years (interquartile range 6.6-14.6). Eighty-four (59%) had undergone previous cardiac operations and 24 (17%) had undergone previous AVR. The median implanted DAH diameter was 21 mm (interquartile range 19-23). The median operation duration was 348 min (227-439) with a median cardiopulmonary bypass time of 212 min (171-257) and a median cross-clamp time of 135 min (113-164). After a median follow-up of 5.3 years (3.3-7.2, max. 15.2 years), the primary efficacy end-points peak gradient (median 14 mmHg, 9-28) and regurgitation (median 0.5, interquartile range 0-1, grade 0-3) showed good results but an increase over time. Freedom from death/explantation/endocarditis/bleeding/thromboembolism at 5 years were 97.8 ± 1.2/88.7 ± 3.3/99.1 ± 0.9/100 and 99.2 ± 0.8%, respectively. Freedom from death/explantation/endocarditis/bleeding/thromboembolism at 10 years were 96.3 ± 1.9/67.1 ± 8.0/93.6 ± 3.9/98.6 ± 1.4 and 86.9 ± 11.6%, respectively. In total, 21 DAH were explanted. Seven were replaced by a mechanical AVR, 1 Ross operation was performed and a re-do DAH was implanted in 13 patients with no redo mortality. The calculated expected adverse events were lower for DAH compared to cryopreserved homograft patients (mean age 8.4 years), and in the same range as for Ross patients (9.2 years) and mechanical AVR (13.0 years). CONCLUSIONS: This large-scale prospective analysis demonstrates excellent mid-term survival using DAH with adverse event rates comparable to paediatric Ross procedures.

Five-year results from a prospective, single-arm European trial on decellularized allografts for aortic valve replacement-the ARISE Study and ARISE Registry Data.

OBJECTIVES: Decellularized aortic homografts (DAH) were introduced as a new option for aortic valve replacement for young patients. METHODS: A prospective, EU-funded, single-arm, multicentre study in 8 centres evaluating non-cryopreserved DAH for aortic valve replacement. RESULTS: A total of 144 patients (99 male) were prospectively enrolled in the ARISE Trial between October 2015 and October 2018 with a median age of 30.4 years [interquartile range (IQR) 15.9-55.1]; 45% had undergone previous cardiac operations, with 19% having 2 or more previous procedures. The mean implanted DAH diameter was 22.6 mm (standard deviation 2.4). The median operation duration was 312 min (IQR 234-417), the median cardiopulmonary bypass time was 154 min (IQR 118-212) and the median cross-clamp time 121 min (IQR 93-150). No postoperative bypass grafting or renal replacement therapy were required. Two early deaths occurred, 1 due to a LCA thrombus on day 3 and 1 due ventricular arrhythmia 5 h postoperation. There were 3 late deaths, 1 death due to endocarditis 4 months postoperatively and 2 unrelated deaths after 5 and 7 years due to cancer and Morbus Wegener resulting in a total mortality of 3.47%. After a median follow-up of 5.9 years [IQR 5.1-6.4, mean 5.5 years. (standard deviation 1.3) max. 7.6 years], the primary efficacy end-points peak gradient with median 11.0 mmHg (IQR 7.8-17.6) and regurgitation of median 0.5 (IQR 0-0.5) of grade 0-3 were excellent. At 5 years, freedom from death/reoperation/endocarditis/bleeding/thromboembolism were 97.9%/93.5%/96.4%/99.2%/99.3%, respectively. CONCLUSIONS: The 5-year results of the prospective multicentre ARISE trial continue to show DAH to be safe for aortic valve replacement with excellent haemodynamics.

Matched comparison of decellularized homografts and bovine jugular vein conduits for pulmonary valve replacement in congenital heart disease.

For decades, bovine jugular vein conduits (BJV) and classic cryopreserved homografts have been the two most widely used options for pulmonary valve replacement (PVR) in congenital heart disease. More recently, decellularized pulmonary homografts (DPH) have provided an alternative avenue for PVR. Matched comparison of patients who received DPH for PVR with patients who received bovine jugular vein conduits (BJV) considering patient age group, type of heart defect, and previous procedures. 319 DPH patients were matched to 319 BJV patients; the mean age of BJV patients was 15.3 (SD 9.5) years versus 19.1 (12.4) years in DPH patients (p = 0.001). The mean conduit diameter was 24.5 (3.5) mm for DPH and 20.3 (2.5) mm for BJV (p < 0.001). There was no difference in survival rates between the two groups after 10 years (97.0 vs. 98.1%, p = 0.45). The rate of freedom from endocarditis was significantly lower for BJV patients (87.1 vs. 96.5%, p = 0.006). Freedom from explantation was significantly lower for BJV at 10 years (81.7 vs. 95.5%, p = 0.001) as well as freedom from any significant degeneration at 10 years (39.6 vs. 65.4%, p < 0.001). 140 Patients, matched for age, heart defect type, prior procedures, and conduit sizes of 20-22 mm (± 2 mm), were compared separately; mean age BJV 8.7 (4.9) and DPH 9.5 (7.3) years (p = n.s.). DPH showed 20% higher freedom from explantation and degeneration in this subgroup (p = 0.232). Decellularized pulmonary homografts exhibit superior 10-year results to bovine jugular vein conduits in PVR.

Minimally Invasive Mitral Valve Surgery in the Elderly.

BACKGROUND: The minimally invasive mitral valve procedure warrants minimal surgical trauma and might influence the postoperative course positively, especially in old patients. In this retrospective study, we reviewed our experience in minimally invasive mitral valve surgery (miMVS) in patients aged ≥ 75 years. METHODS: In this retrospective cohort study, based on propensity score matching, we compared patients aged ≥75 years with patients aged <75 years who underwent miMVS. The primary endpoint was 30-day mortality. Secondary endpoints were myocardial infarction, stroke, and renal failure. RESULTS: Between January 2011 and February 2021, 761 patients underwent miMVS at our institution. After propensity score matching, a study group (≥75 years, n = 189) and a control group (<75 years, n = 189) were formed. Preoperatively patients ≥75 years more often suffered from NYHA III heart failure (60 vs. 46%; p = 0.013). Their valves were more often frequently replaced (48 vs. 32%; p < 0.001), and their postoperative ventilation time was longer (13 hours vs. 11 hours; p < 0.001). There were no statistically significant differences regarding postoperative stroke (3 vs. 0.6%; p = 0.16), myocardial infarction (0 vs. 1%; p = 0.32), renal insufficiency with new dialysis (5 vs. 4%; p = 0.62), and 30-day mortality (4 vs. 2%; p = 0.56). CONCLUSION: miMVS results in satisfactory early postoperative outcomes in elderly patients.

Stabilizing A Vascularized Autologous Matrix with Flexible Magnesium Scaffolds to Reconstruct Dysfunctional Left Ventricular Myocardium in a Large-Animal Feasibility Study.

The surgical reconstruction of dysfunctional myocardium is necessary for patients with severe heart failure. Autologous biomaterials, such as vascularized patch materials, have a regenerative potential due to in vivo remodeling. However, additional temporary mechanical stabilization of the biomaterials is required to prevent aneurysms or rupture. Degradable magnesium scaffolds could prevent these life-threatening risks. A left ventricular transmural defect was reconstructed in minipigs with a piece of the autologous stomach. Geometrically adaptable and degradable scaffolds made of magnesium alloy LA63 were affixed on the epicardium to stabilize the stomach tissue. The degradation of the magnesium structures, their biocompatibility, physiological remodeling of the stomach, and the heart's function were examined six months after the procedure via MRI (Magnetic Resonance Imaging), angiography, µ-CT, and light microscopy. All animals survived the surgery. Stable physiological integration of the stomach patch could be detected. No ruptures of the grafts occurred. The magnesium scaffolds showed good biocompatibility. Regenerative surgical approaches for treating severe heart failure are a promising therapeutic alternative to the currently available, far from optimal options. The temporary mechanical stabilization of viable, vascularized grafts facilitates their applicability in clinical scenarios.

Left Ventricular Wall Reconstruction with Autologous Vascularized Tunica Muscularis of Stomach in a Porcine Pilot Model.

INTRODUCTION: Surgical replacement of dysfunctional cardiac muscle with regenerative tissue is an important option to combat heart failure. But, current available myocardial prostheses like a Dacron or a pericardium patch neither have a regenerative capacity nor do they actively contribute to the heart's pump function. This study aimed to show the feasibility of utilizing a vascularized stomach patch for transmural left ventricular wall reconstruction. METHODS: A left ventricular transmural myocardial defect was reconstructed by performing transdiaphragmatic autologous transplantation of a vascularized stomach segment in six Lewe minipigs. Three further animals received a conventional Dacron patch as a control treatment. The first 3 animals were followed up for 3 months until planned euthanasia, whereas the observation period for the remaining 3 animals was scheduled 6 months following surgery. Functional assessment of the grafts was carried out via cardiac magnetic resonance tomography and angiography. Physiological remodeling was evaluated histologically and immunohistochemically after heart explantation. RESULTS: Five out of six test animals and all control animals survived the complex surgery and completed the follow-up without clinical complications. One animal died intraoperatively due to excessive bleeding. No animal experienced rupture of the stomach graft. Functional integration of the heterotopically transplanted stomach into the surrounding myocardium was observed. Angiography showed development of connections between the gastric graft vasculature and the coronary system of the host cardiac tissue. CONCLUSIONS: The clinical results and the observed physiological integration of gastric grafts into the cardiac structure demonstrate the feasibility of vascularized stomach tissue as myocardial prosthesis. The physiological remodeling indicates a regenerative potential of the graft. Above all, the connection of the gastric vessels with the coronary system constitutes a rationale for the use of vascularized and, therefore, viable stomach tissue for versatile tissue engineering applications.

Optimal reperfusion strategy in acute high-risk pulmonary embolism requiring extracorporeal membrane oxygenation support: a systematic review and meta-analysis.

BACKGROUND: The optimal pulmonary revascularisation strategy in high-risk pulmonary embolism (PE) requiring implantation of extracorporeal membrane oxygenation (ECMO) remains controversial. METHODS: We conducted a systematic review and meta-analysis of evidence comparing mechanical embolectomy and other strategies, including systemic thrombolysis, catheter-directed thrombolysis or ECMO as stand-alone therapy, with regard to mortality and bleeding outcomes. RESULTS: We identified 835 studies, 17 of which were included, comprising 327 PE patients. Overall, 32.4% were treated with mechanical pulmonary reperfusion (of whom 85.9% had surgical embolectomy), while 67.6% received other strategies. The mortality rate was 22.6% in the mechanical reperfusion group and 42.8% in the "other strategies" group. The pooled odds ratio for mortality with mechanical reperfusion was 0.439 (95% CI 0.237-0.816) (p=0.009; I2=35.2%) versus other reperfusion strategies and 0.368 (95% CI 0.185-0.733) (p=0.004; I2=32.9%) for surgical embolectomy versus thrombolysis. The rate of bleeding in patients under ECMO was 22.2% in the mechanical reperfusion group and 19.1% in the "other strategies" group (OR 1.27, 95% CI 0.54-2.96; I2=7.7%). The meta-regression model did not identify any relationship between the covariates "more than one pulmonary reperfusion therapy", "ECMO implantation before pulmonary reperfusion therapy", "clinical presentation of PE" or "cancer-associated PE" and the associated outcomes. CONCLUSIONS: The results of the present meta-analysis and meta-regression suggest that mechanical reperfusion, notably by surgical embolectomy, may yield favourable results regardless of the timing of ECMO implantation in the reperfusion timeline, independent of thrombolysis administration or cardiac arrest presentation.

5-Year results from the prospective European multi-centre study on decellularized homografts for pulmonary valve replacement ESPOIR Trial and ESPOIR Registry data.

OBJECTIVES: Early results from the prospective ESPOIR Trial have indicated excellent results for pulmonary valve replacement using decellularized pulmonary homografts (DPH). METHODS: A 5-year analysis of ESPOIR Trial patients was performed to provide an insight into the midterm DPH performance. ESPOIR Trial and Registry patients were matched with cryopreserved homografts (CH) patients considering patient age, type of heart defect and previous procedures to present the overall experience with DPH. RESULTS: A total of 121 patients (59 female) were prospectively enrolled (8/2014-12/2016), median age 16.5 years (interquartile range 11.2-29.8), and median DPH diameter 24 mm. One death (73 year-old) occurred during a median follow-up of 5.9 years (5.4-6.4), in addition to 2 perioperative deaths resulting in an overall mortality rate of 2.5%. One case of endocarditis in 637 patient-years was noticed, resulting in an incidence of 0.15% per patient-year. At 5 years, the mean peak gradient was 19.9 mmHg (9.9), mean regurgitation 0.9 (0.6, grade 0-3) and freedom from explantation/any reintervention 97.5% (1.5). The combined DPH cohort, n = 319, comprising both Trial and Registry data, showed significantly better freedom from explantation for DPH 95.5% (standard deviation 1.7) than CH 83.0% (2.8) (P < 0.001) and less structural valve degeneration at 10 years when matched to 319 CH patients [DPH 65.5% (standard deviation 4.4) and CH 47.3% (3.7), P = 0.11]. CONCLUSIONS: The 5-year data of the prospective ESPOIR Trial show excellent performance for DPH and low rates of adverse events. ESPOIR Registry data up to 15 years, including a matched comparison with CH, demonstrated statistically significant better freedom from explantation.

Surgery for infective endocarditis following low-intermediate risk transcatheter aortic valve replacement-a multicentre experience.

OBJECTIVES: With the expansion of transcatheter aortic valve replacement (TAVR) into intermediate and low risk, the number of TAVR procedures is bound to rise and along with it the number of cases of infective endocarditis following TAVR (TIE). The aim of this study was to review a multicentre experience of patients undergoing surgical intervention for TIE and to analyse the underlying indications and operative results. METHODS: We retrospectively identified and analysed 69 patients who underwent cardiac surgery due to TIE at 9 cardiac surgical departments across Germany. The primary outcome was operative mortality, 6-month and 1-year survival. RESULTS: Median age was 78 years (72-81) and 48(69.6%) were male. The median time to surgical aortic valve replacement was 14 months (5-24) after TAVR, with 32 patients (46.4%) being diagnosed with early TIE. Cardiac reoperations were performed in 17% of patients and 33% underwent concomitant mitral valve surgery. The main causative organisms were: Enterococcus faecalis (31.9%), coagulase-negative Staphylococcus spp. (26.1%), Methicillin-sensitive Staphylococcus aureus (15.9%) and viridians group streptococci (14.5%). Extracorporeal life support was required in 2 patients (2.9%) for a median duration of 3 days. Postoperative adverse cerebrovascular events were observed in 13 patients (18.9%). Postoperatively, 9 patients (13.0%) required a pacemaker and 33 patients (47.8%) needed temporary renal replacement therapy. Survival to discharge was 88.4% and survival at 6 months and 1 year was found to be 68% and 53%, respectively. CONCLUSIONS: Our results suggest that TIE can be treated according to the guidelines for prosthetic valve endocarditis, namely with early surgery. Surgery for TIE is associated with acceptable morbidity and mortality rates. Surgery should be discussed liberally as a treatment option in patients with TIE by the 'endocarditis team' in referral centres.

4D-flow cardiac magnetic resonance imaging after aortic root replacement with long-valved decellularized aortic homografts: comparison to valve-sparing aortic root replacement and healthy controls.

OBJECTIVES: Long-valved decellularized aortic homografts (DAH) may be used in young patients to treat aortic valve disease associated with aortic root dilatation, thereby eliminating the need for prosthetic material and anticoagulation. METHODS: Thirty-three male subjects in 3 equally sized cohorts were compared: patients following DAH implantation with a median age of 29 years [interquartile range (IQR) 27.5-37.5], patients post-valve-sparing aortic root replacement (VSARR), median 44 years (IQR 31.5-49) and healthy controls, median 33 years (IQR 28-40, P = 0.228). Time-resolved three-dimensional phase-contrast cardiac magnetic resonance imaging was performed to assess maximum blood flow velocity, pulse wave velocity, mechanical energy loss (EL), wall shear stress and flow patterns (vorticity, eccentricity, helicity) in 5 different planes of the aorta. RESULTS: The mean time between surgery and cardiovascular magnetic resonance was 2.56 ± 2.0 years in DAH vs 2.67 ± 2.1 in VSARR, P = 0.500. No significant differences in maximum velocity and pulse wave velocity were found between healthy controls and DAH across all planes. Velocity in the proximal aorta was significantly higher in VSARR (182.91 ± 53.91 cm/s, P = 0.032) compared with healthy controls. EL was significantly higher in VSARR in the proximal aorta with 1.85 mW (IQR 1.39-2.95) compared with healthy controls, 1.06 mW (0.91-1.22, P = 0.016), as well as in the entire thoracic aorta. In contrast, there was no significant EL in DAH in the proximal, 1.27 m/W (0.92-1.53, P = 0.296), as well as in the thoracic aorta, 7.7 m/W (5.25-9.90, P = 0.114), compared with healthy controls. There were no significant differences in wall shear stress parameters for all 5 regions of the thoracic aorta between the 3 groups. DAH patients, however, showed more vorticity, helicity and eccentricity in the ascending aorta compared with healthy controls (P < 0.019). CONCLUSIONS: Decellularized long aortic homografts exhibit near to normal haemodynamic parameters 2.5 years postoperatively compared with healthy controls and VSARR.

Mid-term Outcome of the Edge-To-Edge Mitral Valve Repair Via Aortic Outflow Tract in High-Risk Patients.

The edge-to-edge mitral valve repair technique, invented by Alfieri and colleagues, introduced valve repair as a treatment option for patients with complex diseases where standard annuloplasty and related repair techniques are insufficient, due to annular calcification and patient frailty. We retrospectively evaluated the results of a transaortic edge-to-edge mitral valve repair (Alfieri stitch) in high-risk patients who were undergoing aortic valve replacement. From February, 2012 to December, 2017, 43 patients underwent transaortic edge-to-edge mitral valve repair with concomitant aortic valve replacement at a single institution. Preoperative and postoperative echocardiograms were compared. Home telephone follow up was conducted and postoperative morbidity was examined, including the need for reoperation, stroke and cardiac arrhythmia. 30-day and long-term survival rates were also determined. Mitral regurgitation (MR) was graded semi-quantitatively as 0 (trace and/or none), mild (1), moderate (2) or moderate to severe (3-4). The patients were 74 ± 7.8 years old. 65% of the patients were male. Mean cardiopulmonary bypass time was 115 ± 37 minutes and mean cross-clamp time was 71 ± 23 minutes. There was a significant improvement in preoperative vs postoperative median MR grade (2 (IQR 2-3) vs 0 (IQR 0-1); P = 0.05). Follow-up transthoracic echocardiograms in 29 patients obtained at a median of 9 months' (range 3 - 19 months') and in 16 patients at a median of 34 months' postoperatively (range 21 - 53 months') showed mild (1 (IQR 1-2)) grade of mitral regurgitation. 30-day survival was 98%. Long term survival at 12 and 24 months' were 88% and 81% respectively. Mitral valve reoperation was conducted in 1 patient (2%), who was suffering of endocarditis. Stroke occurred in 2 patients (7%). Cardiac arrhythmia was observed in 15 patients (35%). 8 patients (19%) suffered from atrial fibrillation and 7 patients (16%) displayed atrioventricular blockage. 10 patients (23%) could be treated conservatively and 5 patients (12%) needed implantation of a pacemaker. Transaortic edge-to-edge mitral valve repair can be safely performed during aortic valve replacement in high-risk patients and improves even long-term MR grade. Postoperative cardiac arrhythmia occurs frequently. 66% of them could be treated successfully by conservative procedures.

Comparison of dual-energy computer tomography and dynamic contrast-enhanced MRI for evaluating lung perfusion defects in chronic thromboembolic pulmonary hypertension.

OBJECTIVES: To evaluate the agreement in detecting pulmonary perfusion defects in patients with chronic thromboembolic pulmonary hypertension using dual-energy CT and dynamic contrast-enhanced MRI. Second, to compare both imaging modalities in monitoring lung perfusion changes in these patients after undergoing pulmonary endarterectomy. METHODS: 20 patients were examined with CT and MRI before and/or after pulmonary endarterectomy. Estimated perfusion defect percentage from both modalities was compared in a lobe-based analysis. Spatial agreement of perfusion defect maps was also assessed. RESULTS: A significant correlation between CT and MRI based perfusion defect percentage was calculated in all lung lobes (r > 0.78; p < 0.001). In addition, a good spatial agreement between perfusion defect maps was found (mean spatial overlap for the whole lung was 68.2%; SD = 6.9). Both CT and MRI detected improvements in pulmonary perfusion after pulmonary endarterectomy: 8% and 7% decrease in whole lung perfusion defect percentage (p = 0.007 and 0.004), respectively. In a lobe-wise analysis, improvements were statistically significant only in lower lobes using both modalities (reduction in defect percentage ranged from 16-29%; p < 0.02). CONCLUSIONS: Dual-energy CT is an alternative to MRI in monitoring chronic thromboembolic pulmonary hypertension. Both imaging modalities provided comparable estimations of perfusion defects and could detect similar improvement in lung perfusion after pulmonary endarterectomy.

Residual immune response towards decellularized homografts may be highly individual.

OBJECTIVES: Decellularized homograft valves (DHVs) have shown promising clinical results, particularly in the treatment of congenital heart disease. However, DHV appears to elicit an immune response in a subset of young patients, indicated by early valve degeneration. As the decellularization process is quality controlled for each DHV, we hypothesized that there may be residual immunogenicity within the extracellular matrix of DHV. METHODS: A semi-quantitative dot blot analysis was established to screen for preformed recipient antibodies using secondary anti-human antibodies. Fifteen DHV samples (7 aortic, 8 pulmonary) were solubilized and exposed to serum from 20 healthy controls. RESULTS: The sera from young controls (n = 10, 18-25 years) showed significantly stronger binding of preformed antibodies than sera from older individuals (n = 10, 48-73 years). The difference between the means of arbitrary units was 15.1 ± 6.5 (P = 0.0315). There was high intraindividual variance in the mean amounts of arbitrary units of antibody binding with some healthy controls showing >10 times higher antibody binding towards 2 different DHV. The amount of preformed antibodies bound to DHVs was higher in aortic than in pulmonary DHVs. The mean number of antibody binding (in arbitrary units) was 17.2 ± 4.5 in aortic and 14.5 ± 4.7 in pulmonary DHV (P = 0.27). The amount of preformed antibodies bound to pulmonary DHVs was statistically significantly higher in the sera of healthy males (n = 10) than in the sera of healthy females (n = 10). The mean number of arbitrary units was 17.2 ± 4.2 in male and 11.7 ± 5.3 in female sera (P = 0.036). Antibody binding to aortic DHV was also higher in males, but not significant (18.8 ± 5.0 vs 15.6 ± 4.0). Blood group (ABO) incompatibility between the serum from controls and DHV showed no impact on antibody binding, and there was no age-related impact among DHV donors. CONCLUSIONS: Residual immunogenicity of decellularized homografts appears to exist despite almost complete cell removal. The established dot blot method allows a semi-quantitative assessment of the individual immune response towards extracellular DHV components and potentially the possibility of preoperative homograft matching.

Blood-based protein profiling identifies serum protein c-KIT as a novel biomarker for hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is one of the most common hereditary heart diseases and can be classified into an obstructive (HOCM) and non-obstructive (HNCM) form. Major characteristics for HCM are the hypertrophy of cardiomyocytes and development of cardiac fibrosis. Patients with HCM have a higher risk for sudden cardiac death compared to a healthy population. In the present study, we investigated the abundancy of selected proteins as potential biomarkers in patients with HCM. We included 60 patients with HCM and 28 healthy controls and quantitatively measured the rate of a set of 92 proteins already known to be associated with cardiometabolic processes via protein screening using the proximity extension assay technology in a subgroup of these patients (20 HCM and 10 healthy controls). After validation of four hits in the whole cohort of patients consisting of 88 individuals (60 HCM patients, 28 healthy controls) we found only one candidate, c-KIT, which was regulated significantly different between HCM patients and healthy controls and thus was chosen for further analyses. c-KIT is a tyrosine-protein kinase acting as receptor for the stem cell factor and activating several pathways essential for cell proliferation and survival, hematopoiesis, gametogenesis and melanogenesis. Serum protein levels of c-KIT were significantly lower in patients with HCM than in healthy controls, even after adjusting for confounding factors age and sex. In addition, c-KIT levels in human cardiac tissue of patients with HOCM were significant higher compared to controls indicating high levels of c-KIT in fibrotic myocardium. Furthermore, c-KIT concentration in serum significantly correlated with left ventricular end-diastolic diameter in HOCM, but not HCM patients. The present data suggest c-KIT as a novel biomarker differentiating between patients with HCM and healthy population and might provide further functional insights into fibrosis-related processes of HOCM.

Immunological and functional features of decellularized xenogeneic heart valves after transplantation into GGTA1-KO pigs.

Decellularization of xenogeneic heart valves might lead to excellent regenerative implants, from which many patients could benefit. However, this material carries various xenogeneic epitopes and thus bears a considerable inherent immunological risk. Here, we investigated the regenerative and immunogenic potential of xenogeneic decellularized heart valve implants using pigs deficient for the galactosyltransferase gene (GGTA1-KO) as novel large animal model. Decellularized aortic and pulmonary heart valves obtained from sheep, wild-type pigs or GGTA1-KO pigs were implanted into GGTA1-KO pigs for 3, or 6 months, respectively. Explants were analyzed histologically, immunhistologically (CD3, CD21 and CD172a) and anti-αGal antibody serum titers were determined by ELISA. Xenogeneic sheep derived implants exhibited a strong immune reaction upon implantation into GGTA1-KO pigs, characterized by massive inflammatory cells infiltrates, presence of foreign body giant cells, a dramatic increase of anti-αGal antibody titers and ultimately destruction of the graft, whereas wild-type porcine grafts induced only a mild reaction in GGTA1-KO pigs. Allogeneic implants, wild-type/wild-type and GGTA1-KO/GGTA1-KO valves did not induce a measurable immune reaction. Thus, GGTA1-KO pigs developed a 'human-like' immune response toward decellularized xenogeneic implants showing that immunogenicity of xenogeneic implants is not sufficiently reduced by decellularization, which detracts from their regenerative potential.

Cardiac valve operations after solid organ transplantation: A single-center experience.

OBJECTIVE: Cardiac valve operations in patients who have undergone solid organ transplantation (ie, kidney, liver, pancreas, heart, and lung) pose unique challenges due to patient comorbidities and to the need for immunosuppressive therapy. The aim of this retrospective study was to present our experience with patients with solid-organ transplant who had cardiac valve operation at the time or after transplantation. METHODS: Records of patients who had undergone cardiac valve operations after solid organ transplantation between January 1998 and January 2019 were retrospectively reviewed. Follow-up amounted to a median of 51 months (interquartile range, 5-88 months). RESULTS: Among the 14,465 patients who underwent treatment for a cardiac valvular pathology during the study period, 127 patients (0.9%) had undergone a solid organ transplantation (kidney: n = 9 [76%]; liver: n = 12 [9%]; pancreas: n = 4 [3%]; heart: n = 16 [13%]; lung: n = 9 [7%]). Postoperatively, 14 patients (11%) underwent rethoracotomy for bleeding and 24 patients (19%) required new dialysis treatment. Twenty-five patients (20%) died in-hospital. Postoperative course was worse in patients operated for endocarditis or undergoing concomitant transplantation and valve surgery. Overall survival was 59%, 47%, and 40%, but survival conditioned to hospital discharge was 73%, 58%, and 50% at 5-, 10-, and 15-year follow-up, respectively. Freedom from major valve-related events amounted to 77%, 56%, and 46%, respectively. CONCLUSIONS: Although the high prevalence of postoperative complications, especially in patients with endocarditis or concomitant transplantation and valve surgery, survival conditioned to hospital discharge was satisfactory in patients undergoing valve surgery after solid organ transplantation.

Cardiac Phlegmon: Infectious Endocarditis Causing Ventricular Wall Rupture.

Background Rupture of the cardiac ventricular wall is a rare and essentially lethal complication of infectious endocarditis valvularis. Case Description We report a case of a 49-year-old female patient with infectious endocarditis of the aortic valve. Following aortic valve replacement, the patient developed a sudden free left ventricular wall rupture. Immediate reoperation was successful. Histopathology revealed a myocardial infarction due to septic thromboembolism causing a phlegmonlike myocardial appearance. Conclusion This is a rare case of a myocardial phlegmon with subsequent cardiac lateral wall rupture in the context of an infectious endocarditis with septic coronary embolism.

Perioperative CTEPH patient monitoring with 2D phase-contrast MRI reflects clinical, cardiac and pulmonary perfusion changes after pulmonary endarterectomy.

Magnetic resonance imaging (MRI) is an emerging tool for diagnosis and treatment monitoring of chronic thromboembolic pulmonary hypertension (CTEPH). The current study aims to identify central pulmonary arterial hemodynamic parameters that reflect clinical, cardiac and pulmonary changes after PEA. 31 CTEPH patients, who underwent PEA and received pre- and postoperative MRI, were analyzed retrospectively. Central pulmonary arterial blood flow, lung perfusion and right heart function data were derived from MRI. Mean pulmonary arterial pressure (mPAP) and 5-month follow-up six-minute walk-distance (6MWD) were assessed. After PEA, mPAP decreased significantly and patients achieved a higher 6MWD. Central pulmonary arterial blood flow velocities, pulmonary blood flow (PBF) and right ventricular function increased significantly. Two-dimensional (2D) phase-contrast (PC) MRI-derived average mean velocity, maximum mean velocity and deceleration volume changes after PEA correlated with changes of 6MWD and right heart ejection fraction (RVEF). Deceleration volume is a novel 2D PC MRI parameter showing further correlation with PBF changes. In conclusion, 2D PC MRI-derived main pulmonary hemodynamic changes reflect changes of RVEF, PBF and 5-month follow-up 6MWD and may be used for future CTEPH patient monitoring after PEA.

Targeting muscle-enriched long non-coding RNA H19 reverses pathological cardiac hypertrophy.

AIMS: Pathological cardiac remodelling and subsequent heart failure represents an unmet clinical need. Long non-coding RNAs (lncRNAs) are emerging as crucial molecular orchestrators of disease processes, including that of heart diseases. Here, we report on the powerful therapeutic potential of the conserved lncRNA H19 in the treatment of pathological cardiac hypertrophy. METHOD AND RESULTS: Pressure overload-induced left ventricular cardiac remodelling revealed an up-regulation of H19 in the early phase but strong sustained repression upon reaching the decompensated phase of heart failure. The translational potential of H19 is highlighted by its repression in a large animal (pig) model of left ventricular hypertrophy, in diseased human heart samples, in human stem cell-derived cardiomyocytes and in human engineered heart tissue in response to afterload enhancement. Pressure overload-induced cardiac hypertrophy in H19 knock-out mice was aggravated compared to wild-type mice. In contrast, vector-based, cardiomyocyte-directed gene therapy using murine and human H19 strongly attenuated heart failure even when cardiac hypertrophy was already established. Mechanistically, using microarray, gene set enrichment analyses and Chromatin ImmunoPrecipitation DNA-Sequencing, we identified a link between H19 and pro-hypertrophic nuclear factor of activated T cells (NFAT) signalling. H19 physically interacts with the polycomb repressive complex 2 to suppress H3K27 tri-methylation of the anti-hypertrophic Tescalcin locus which in turn leads to reduced NFAT expression and activity. CONCLUSION: H19 is highly conserved and down-regulated in failing hearts from mice, pigs and humans. H19 gene therapy prevents and reverses experimental pressure-overload-induced heart failure. H19 acts as an anti-hypertrophic lncRNA and represents a promising therapeutic target to combat pathological cardiac remodelling.