We present the long-term results of a trileaflet (Triflo) versus bileaflet (On-X) mechanical valve in both aortic and pulmonary positions in a sheep model. The Triflo valve was implanted in 21 female sheep in aortic (n = 8) and pulmonary position (n = 13). The On-X valve was implanted in 7 female sheep in aortic (n = 1) and pulmonary (n = 6) positions. No antithrombotic medication of any kind was given postoperatively. In the aortic group, survival cohorts were 3 and 5 months. In the pulmonary group, survival cohorts were 10 and 20 weeks. Valve performance was assessed using haematology, echocardiography and acoustic measurements combined with post-mortem pathology analysis of the downstream organs. The mean gradients were lower for the Triflo valve in both pulmonary [4.30 mmHg (3.70–5.73) vs 6.80 mmHg (4.63–7.96), P = 0.012] and aortic [5.1 mmHg (4.2–7.7) vs 10.7 mmHg (8.7–12.9), P = 0.007] positions. Peak gradients were lower for the Triflo valve in both pulmonary [8.05 mmHg (6.75–10.23) vs 13.15 mmHg (9.20–14.76), P = 0.005] and aortic [8.7 mmHg (7.5–12.5) vs 16.5 mmHg (14.2–19.6), P = 0.009] positions. In both positions, leaflets and housing surface were free from any deposits macro- and microscopically and comparable to nonimplanted control valves. Peripheral organs showed no signs of thrombo-embolic damage. Biochemical and haematological were comparable to preoperative. The closing click sound pressure level of the Triflo was significantly lower in both aortic [108.4 sound pressure level (102.0–115.7) vs 111.7 sound pressure level (105.5–117.0), P < 0.001] and pulmonary [103.6 sound pressure level (99.1–108.9) vs 118.5 sound pressure level (116.7–120.2), P < 0.001] position. Preliminary in vivo results of the Triflo valve are promising in both aortic and pulmonary positions in an ovine model. Excellent haemodynamics, stable long-term function, low valve noise and no thrombo-embolic events in the absence of antithrombotic medication lay the foundation to a future clinical first-in-man trial.

OBJECTIVES: Mechanical valves still require life-long anticoagulation. Preclinical animal testing is a crucial step in the assessment of valves; however, the chosen animal model should be carefully considered, and a well-controlled animal model of mechanical valve thrombosis has not been established yet. In this study, a histopathologic comparison was performed to evaluate the representativity of pigs and sheep as large animal models in bileaflet mechanical valve thrombosis research. METHODS: 10 pigs and 8 sheep were implanted with a bileaflet mechanical valve in pulmonary position. During follow-up, no anticoagulative therapy was administered. Pigs were sacrificed between 14 and 38 days for explantation and assessment of the valve. Sheep were sacrificed between 71 and 155 days. Thrombus samples were processed and (immuno)histochemical stainings were applied. A pathologist evaluated the samples morphologically and semiquantitatively and compared these samples to available slides from 3 human patients who underwent redo surgery for acute bileaflet mechanical valve thrombosis, caused by insufficient anticoagulation. RESULTS: All pigs showed macroscopically evident thrombi on the mechanical valve surface at sacrifice. In contrast, none of the sheep showed any sign of thrombus formation. Histology showed a high fibrin content in thrombi of both human and porcine cases (3/3 vs 8/10). Porcine thrombi showed more cellular organization (0/3 vs 6/10), more calcification (0/3 vs 9/10) and more endothelialization (0/3 vs 6/10). Inflammatory cells were present in all samples and were considered physiological. CONCLUSIONS: Contrary to sheep, pigs develop thrombi on their mechanical valves in the short-term if no anticoagulation is administered. Histologic comparison of human and porcine thrombi shows comparable findings. The pig model might serve interestingly for further research on valve thrombosis, if it shows not to be an overly aggressive model.

• The RUA vascular graft is externally sealed with an Elast-Eon polymer. • No animal-derived sealing products such as gelatin are needed. • Safety and performance of the experimental graft was tested in a large animal model. • Similar results were obtained in the experimental group and the control group. • The experimental graft elicited a nonadherent external fibrous capsule.

OBJECTIVES: Little is known of the haemodynamic changes following chronic ventricular volume deprivation, which impact understanding the disease course and treatment results. An animal model was created to study the effects of chronic ventricular volume deprivation and acute reloading. METHODS: In 13 lambs, a polytetrafluoroethylene strip was placed around the inferior and superior caval vein through thoracotomy resulting in progressive ventricular volume deprivation during growth. After 10 months, the polytetrafluoroethylene bands were relieved. Magnetic resonance imaging and haemodynamic measurements including pressure–volume loops were performed before and after debanding and compared to age and weight-matched controls (n = 6). RESULTS: The end-diastolic pressure was elevated compared to healthy animals (median [interquartile range] 8.1 [7.2–9.1] vs 1.0 [1.0–2.7] mmHg, P 0.030). The end-diastolic pressure after debanding increased to 11.1 (10.4–17.2) mmHg, P 0.038. The end-diastolic volume and end-systolic volume of the intervention group were also significantly less than the healthy controls (71.5 [66.7–74.7] vs 81.5 [74.3–86.3] ml, P 0.004 and 34.5 [27.5–37.6] vs 42.7 [35.0–50.5] ml P 0.001). The end-diastolic pressure–volume relationship was significantly shifted upwards and to the left compared to controls, indicative of a decreased compliance of the chronically deprived left ventricle. Histologic assessment revealed no significant differences in fibrosis between the ventricles of the intervention group and healthy animals. CONCLUSIONS: When a healthy ventricle is chronically deprived of an adequate preload, it becomes less compliant with elevated filling pressures. Acute reloading does not lead to ventricular systolic dysfunction, but in the early phase, diastolic pressure may rise. A better understanding of this phenomenon might help to recognition and treatment of impaired ventricular compliance.

The mechanism underlying myopericarditis associated with mRNA COVID-19 vaccination, including increased susceptibility in young males, remains poorly understood. This study aims to explore the hypothesis that engaging in physical exercise at the time of mRNA COVID-19 vaccination may promote a cardiac inflammatory response, leading to the development of myopericarditis. Male BALB/c mice underwent treadmill running or remained sedentary for five weeks. Subsequently, two doses of the Pfizer/BioNTech vaccine or vehicle were administered with a 14-day interval, while the exercise regimen continued. The animals were euthanized days after the second vaccination. Vaccination was followed by body weight loss, increased hepatic inflammation, and an antigen-specific T cell response. Small foci of fibrovascular inflammation and focal cell loss were observed in the right ventricle, irrespective of vaccination and/or exercise. Vaccination did not elevate cardiac troponin levels. Cardiac tissue from the vaccinated mice showed upregulated mRNA expression of the genes IFNγ and IL-1β, but not IL-6 or TNFα. This pro-inflammatory signature in the heart was not exacerbated by endurance exercise. Ex vivo vascular reactivity remained unaffected by vaccination. Our data provide evidence for the cardiac safety of mRNA COVID-19 vaccination. The role of exercise in the development of pro-inflammatory cardiac changes post mRNA vaccination could not be established.