The study was approved by the institutional review board (IRB) at the University Medical Center Campus Kiel, Kiel, Germany (reference number: AZ D 559/18) and registered at the German Clinical Trials Register (reference number: DRKS00022222). Objective. Unilateral pulmonary edema (UPE) is a complication after minimally invasive mitral valve surgery (MIMVS). We analyzed the impact of this complication on the short- and long-term outcome over a 10-year period. Methods. We retrospectively observed 393 MIMVS patients between 01/2009 and 12/2019. The primary endpoint was a radiographically and clinically defined UPE within the first postoperative 24 h, secondary endpoints were 30-day and long-term mortality and the percentage of patients requiring ECLS. Risk factors for UPE incidence were evaluated by logistic regression, and risk factors for mortality in the follow-up period were assessed by Cox regression. Results. Median EuroSCORE II reached 0.98% in the complete MIMVS group. Combined 30-day and in-hospital mortality after MIMVS was 2.0% with a 95, 93 and 77% survival rate after 1, 3 and 10 years. Seventy-two (18.3%) of 393 patients developed a UPE 24 h after surgery. Six patients (8.3%) with UPE required an extracorporeal life-support system. Logistic regression analysis identified a higher creatinine level, a worse LV function, pulmonary hypertension, intraoperative transfusion and a longer aortic clamp time as predictors for UPE. Combined in hospital mortality and 30-day mortality was slightly but not significantly higher in the UPE group (4.2 vs. 1.6%; p = 0.17). Predictors for mortality during follow-up were age ≥ 70 years, impaired RVF, COPD, drainage loss ≥ 800 mL and length of ventilation ≥ 48 h. During a median follow-up of 4.6 years, comparable survival between UPE and non-UPE patients was seen in our analysis after 5 years (89 vs. 88%; p = 0.98). Conclusions. In-hospital outcome with UPE after MIMVS was not significantly worse compared to non-UPE patients, and no differences were observed in the long-term follow-up. However, prolonged aortic clamp time, worse renal and left ventricular function, pulmonary hypertension and transfusion are associated with UPE.

Objective: A small number of transcatheter mitral valve implants (TMVIs) have been reported using devices designed to treat secondary mitral regurgitation (MR). However, MR has many etiologies, and patients have a broad spectrum of annular size, geometry, and lesions. There are a number of technical challenges for TMVI including left ventricular outflow tract obstruction and paravalvular MR. Thirty days’ outcome of first-in-man implants with a novel TMVI device is reported. Methods: The Tendyne TMVI system consists of a porcine pericardial valve in a tethered nitinol frame. An apical tether fixed to an epicardial pad stabilizes the device. The device is fully repositionable and retrievable even after complete deployment. Preoperative assessment was performed with 3-dimensional (3D) transesophageal echocardiogram and multislice computed tomography to define annular dimensions, geometry, and guide surgical access. Three patients were deemed not to be candidates for conventional surgery or for treatment with any Conformitè Européenne-marked device by Heart Team Evaluation. They were a 68-year-old woman with prior coronary artery bypass grafts and severe functional MR; a 75-year-old man with prior coronary bypass grafts, significant renal dysfunction, and severe degenerative MR; and a frail 86-year-old man with severe degenerative MR. Each had a TMVI via a transapical approach through a left minithoracotomy. Apical tether tension was adjusted to optimize device position. Results: Implantation was guided by 2D and 3D transesophageal echocardiogram. The apical pad facilitated LV apical closure. There were no procedural complications. No patient had hemodynamically significant residual MR or left ventricular outflow tract obstruction, and there was no significant mitral gradient. All patients were discharged to their own home (the third on the fifth postoperative day), all with significant improvement in their symptoms. All were alive and well 30 days after implant. Two patients with existing conduction abnormalities had cardiac resynchronisation therapy after the procedure, and one patient had para valvular leak (PVL) with evidence of hemolysis at 30 days, which reduced in severity with conservative treatment. Conclusions: The first-in-man experience with the Tendyne TMVI system is promising. Valve stabilization by an apical tether is a novel way to address some of the challenges of TMVI. The unique Tendyne design features may offer potential for its use across a wide range of mitral valve pathologies.

Clinically used heart valve prostheses, despite their progress, are still associated with limitations. Biodegradable poly-ε-caprolactone (PCL) nanofiber scaffolds, as a matrix, were seeded with human endothelial colony-forming cells (ECFCs) and human induced-pluripotent stem cells-derived MSCs (iMSCs) for the generation of tissue-engineered heart valves. Cell adhesion, proliferation, and distribution, as well as the effects of coating PCL nanofibers, were analyzed by fluorescence microscopy and SEM. Mechanical properties of seeded PCL scaffolds were investigated under uniaxial loading. iPSCs were used to differentiate into iMSCs via mesoderm. The obtained iMSCs exhibited a comparable phenotype and surface marker expression to adult human MSCs and were capable of multilineage differentiation. EFCFs and MSCs showed good adhesion and distribution on PCL fibers, forming a closed cell cover. Coating of the fibers resulted in an increased cell number only at an early time point; from day 7 of colonization, there was no difference between cell numbers on coated and uncoated PCL fibers. The mechanical properties of PCL scaffolds under uniaxial loading were compared with native porcine pulmonary valve leaflets. The Young’s modulus and mean elongation at F_max of unseeded PCL scaffolds were comparable to those of native leaflets (p = ns.). Colonization of PCL scaffolds with human ECFCs or iMSCs did not alter these properties (p = ns.). However, the native heart valves exhibited a maximum tensile stress at a force of 1.2 ± 0.5 N, whereas it was lower in the unseeded PCL scaffolds (0.6 ± 0.0 N, p < 0.05). A closed cell layer on PCL tissues did not change the values of F_max (ECFCs: 0.6 ± 0.1 N; iMSCs: 0.7 ± 0.1 N). Here, a successful two-phase protocol, based on the timed use of differentiation factors for efficient differentiation of human iPSCs into iMSCs, was developed. Furthermore, we demonstrated the successful colonization of a biodegradable PCL nanofiber matrix with human ECFCs and iMSCs suitable for the generation of tissue-engineered heart valves. A closed cell cover was already evident after 14 days for ECFCs and 21 days for MSCs. The PCL tissue did not show major mechanical differences compared to native heart valves, which was not altered by short-term surface colonization with human cells in the absence of an extracellular matrix.

One of the most important medical interventions for individuals with heart valvular disease is heart valve replacement, which is not without substantial challenges, particularly for pediatric patients. Due to their biological properties and biocompatibility, natural tissue-originated scaffolds derived from human or animal sources are one type of scaffold that is widely used in tissue engineering. However, they are known for their high potential for immunogenicity. Being free of cells and genetic material, decellularized xenografts, consequently, have low immunogenicity and, thus, are expected to be tolerated by the recipient’s immune system. The scaffold ultrastructure and ECM composition can be affected by cell removal agents. Therefore, applying an appropriate method that preserves intact the structure of the ECM plays a critical role in the final result. So far, there has not been an effective decellularization technique that preserves the integrity of the heart valve’s ultrastructure while securing the least amount of genetic material left. This study demonstrates a new protocol with untraceable cells and residual DNA, thereby maximally reducing any chance of immunogenicity. The mechanical and biochemical properties of the ECM resemble those of native heart valves. Results from this study strongly indicate that different critical factors, such as ionic detergent omission, the substitution of Triton X-100 with Tergitol, and using a lower concentration of trypsin and a higher concentration of DNase and RNase, play a significant role in maintaining intact the ultrastructure and function of the ECM.

Over the last two decades, transcatheter devices have been developed to repair or replace diseased mitral valves (MV). Transcatheter mitral valve repair (TMVr) devices have been proven to be efficient and safe, but many anatomical structures are not compatible with these technologies. The most significant advantage of transcatheter mitral valve replacement (TMVR) over transcatheter repair is the greater and more reliable reduction in mitral regurgitation. However, there are also potential disadvantages. This review introduces the newest TMVr and TMVR devices and presents clinical trial data to identify current challenges and directions for future research.

Background: Elevated pre-procedural high-sensitivity troponin T (hs-TnT) levels predict adverse outcomes in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). It is unknown whether elevated troponin levels still provide prognostic information during follow-up after successful TAVR. We evaluated the long-term implications of elevated hs-TnT levels found at 1-year post-TAVR. Methods and results: The study included 349 patients who underwent TAVR for severe AS from 2010–2019 and for whom 1-year hs-TnT levels were available. Any required percutaneous coronary interventions were performed > 1 week before TAVR. The primary endpoint was survival time starting at 1-year post-TAVR. Optimal hs-TnT cutoff for stratifying risk, identified by ROC analysis, was 39.4 pg/mL. 292 patients had hs-TnT < 39.4 pg/mL (median 18.3 pg/mL) and 57 had hs-TnT ≥ 39.4 pg/mL (median 51.2 pg/mL). The high hs-TnT group had a higher median N-terminal pro-B-type natriuretic peptide (NT-proBNP) level, greater left ventricular (LV) mass, higher prevalence of severe diastolic dysfunction, LV ejection fraction < 35%, severe renal dysfunction, and more men compared with the low hs-TnT group. All-cause mortality during follow-up after TAVR was significantly higher among patients who had hs-TnT ≥ 39.4 pg/mL compared with those who did not (mortality rate at 2 years post-TAVR: 12.3% vs. 4.1%, p = 0.010). Multivariate analysis identified 1-year hs-TnT ≥ 39.4 pg/mL (hazard ratio 2.93, 95% CI 1.91–4.49, p < 0.001), NT-proBNP level > 300 pg/mL, male sex, an eGFR < 60 mL/min/1.73 m² and chronic obstructive pulmonary disease as independent risk factors for long-term mortality after TAVR. Conclusions: Elevated hs-TnT concentrations at 1-year after TAVR were associated with a higher long-term mortality. Graphic