Injectable living marrow stromal cell-based autologous tissue engineered heart valves: first experiences with a one-step intervention in primates

Aims A living heart valve with regeneration capacity based on autologous cells and minimally invasive implantation technology would represent a substantial improvement upon contemporary heart valve prostheses. This study investigates the feasibility of injectable, marrow stromal cell-based, autologous, living tissue engineered heart valves (TEHV) generated and implanted in a one-step intervention in non-human primates. Methods and results Trileaflet heart valves were fabricated from non-woven biodegradable synthetic composite scaffolds and integrated into self-expanding nitinol stents. During the same intervention autologous bone marrow-derived mononuclear cells were harvested, seeded onto the scaffold matrix, and implanted transapically as pulmonary valve replacements into non-human primates (n = 6). The transapical implantations were successful in all animals and the overall procedure time from cell harvest to TEHV implantation was 118 ± 17 min. In vivo functionality assessed by echocardiography revealed preserved valvular structures and adequate functionality up to 4 weeks post implantation. Substantial cellular remodelling and in-growth into the scaffold materials resulted in layered, endothelialized tissues as visualized by histology and immunohistochemistry. Biomechanical analysis showed non-linear stress-strain curves of the leaflets, indicating replacement of the initial biodegradable matrix by living tissue. Conclusion Here, we provide a novel concept demonstrating that heart valve tissue engineering based on a minimally invasive technique for both cell harvest and valve delivery as a one-step intervention is feasible in non-human primates. This innovative approach may overcome the limitations of contemporary surgical and interventional bioprosthetic heart valve prosthese

Trajectory of coronary motion and its significance in robotic motion cancellation

Objectives: To characterize remaining coronary artery motion of beating pig hearts after stabilization with an ?Octopus? using an optical remote analysis technique. Methods: Three pigs (40, 60 and 65 kg) underwent full sternotomy after receiving general anesthesia. An 8-bit high speed black and white video camera (50 frames/s) coupled with a laser sensor (60 m resolution) were used to capture heart wall motion in all three dimensions. Dopamine infusion was used to deliberately modulate cardiac contractility. Synchronized ECG, blood pressure, airway pressure and video data of the region around the first branching point of the left anterior descending (LAD) coronary artery after Octopus stabilization were captured for stretches of 8 s each. Several sequences of the same region were captured over a period of several minutes. Computerized off-line analysis allowed us to perform minute characterization of the heart wall motion. Results: The movement of the points of interest on the LAD ranged from 0.22 to 0.81 mm in the lateral plane (x/y-axis) and 0.5?2.6 mm out of the plane (z-axis). Fast excursions (<50 m/s in the lateral plane) occurred corresponding to the QRS complex and the T wave; while slow excursion phases

Propensity Matched Outcomes of Minimally Invasive Mitral Surgery: Does a Heart-Team Approach Eliminate Female Gender as an Independent Risk Factor?

Background: There is increasing evidence that female gender is an independent risk factor for cardiac surgery. Minimally invasive mitral surgery (MIV) has proven to have excellent long-term results, but little is known about gender-dependent outcomes. The aim of our study was to analyze our heart team's decision-based MIV-specialized cohort. Methods: In-hospital and follow-up data were retrospectively collected. The cohort was divided into gender groups and propensity-matched groups. Results: Between 22 July 2013 and 31 December 2022, 302 consecutive patients underwent MIV. Before matching, the total cohort showed that women were older, had a higher EuroSCORE II, were more symptomatic, and had more complex valve pathology and tricuspid regurgitation resulting in more valve replacements and tricuspid repairs. Intensive and hospital stays were longer. In-hospital deaths (n = 3, all women) were comparable, with more atrial fibrillation in women. The median follow-up time was 3.44 (0.008–8.9) years. The ejection fraction, NYHA, and recurrent regurgitation were low and comparable and atrial fibrillation more frequent in women. The calculated 5-year survival and freedom from re-intervention were comparable (p = 0.9 and p = 0.2). Propensity matching compared 101 well-balanced pairs; women still had fewer resections and more atrial fibrillation. During the follow-up, women had a better ejection fraction. The calculated 5-year survival and freedom from re-intervention were comparable (p = 0.3 and p = 0.3). Conclusions: Despite women being older and sicker, with more complex valve pathology and subsequent replacement, early and mid-term mortality and the need for reoperation were low and comparable before and after propensity matching, which might be the result of the MIV setting combined with our patient-tailored decision-making. We believe that a multidisciplinary heart team approach is crucial to optimize patient outcomes in MIV, and it might also reduce the widely reported increased surgical risk in female patients. Further studies are needed to prove our findings

Severe cardiomyopathy following treatment with the tumour necrosis factor-alpha inhibitor adalimumab for Crohn's disease

Adalimumab belongs to the group of tumour necrosis factor-alpha inhibitors and has been approved for the treatment Crohn's Disease since 2007. Herein we report a severe adverse reaction to adalimumab in a 25-year-old female patient. One week after the initial-dose of adalimumab (160 mg), which was initiated due to an acute exacerbation of Crohn's disease, the patient developed a fulminant cardiomyopathy. In severe cardiogenic shock, the patient required an extracorporeal membrane-oxygenation system for 8 days until cardiac recovery

Injectable living marrow stromal cell-based autologous tissue engineered heart valves: first experiences with a one-step intervention in primates

Aims A living heart valve with regeneration capacity based on autologous cells and minimally invasive implantation technology would represent a substantial improvement upon contemporary heart valve prostheses. This study investigates the feasibility of injectable, marrow stromal cell-based, autologous, living tissue engineered heart valves (TEHV) generated and implanted in a one-step intervention in non-human primates. Methods and results Trileaflet heart valves were fabricated from non-woven biodegradable synthetic composite scaffolds and integrated into self-expanding nitinol stents. During the same intervention autologous bone marrow-derived mononuclear cells were harvested, seeded onto the scaffold matrix, and implanted transapically as pulmonary valve replacements into non-human primates (n = 6). The transapical implantations were successful in all animals and the overall procedure time from cell harvest to TEHV implantation was 118 ± 17 min. In vivo functionality assessed by echocardiography revealed preserved valvular structures and adequate functionality up to 4 weeks post implantation. Substantial cellular remodelling and in-growth into the scaffold materials resulted in layered, endothelialized tissues as visualized by histology and immunohistochemistry. Biomechanical analysis showed non-linear stress-strain curves of the leaflets, indicating replacement of the initial biodegradable matrix by living tissue. Conclusion Here, we provide a novel concept demonstrating that heart valve tissue engineering based on a minimally invasive technique for both cell harvest and valve delivery as a one-step intervention is feasible in non-human primates. This innovative approach may overcome the limitations of contemporary surgical and interventional bioprosthetic heart valve prostheses