Background: Glutaraldehyde fixation does not guarantee complete tissue biocompatibility in current clinical bioprosthetic heart valves (BHVs). Particularly, circulating anti‐αGal human antibodies increase significantly from just 10 days after a BHV implantation. The inactivation of such epitope should be mandatory to meet the requirements for a perspectively safe clinical application; nevertheless, its quantitative assessment in commercially available BHVs has never been carried out.Methods: In this investigation, seven different models of BHVs were tested. The number of epitopes was determined with reference to a standard αGal source by an ELISA test. The presence of xenoantigen was subsequently confirmed by immunofluorescence analysis. Porcine tissue, knockout for the αGal epitopes, was used as negative control.Results: Epic™ valve was the only model among those tested, in which the αGal antigen appeared to be completely shielded. Composite Trifecta™ valve exhibited conflicting results: cusps of bovine pericardial tissue were devoid of reactive αGal epitopes, while the stent cover strip of porcine pericardium still maintained 30% of active antigens originally present in native tissue. All other tested BHVs express an αGal amount not significantly different from that exhibited by porcine Mosaic^® valve (5.2 ± 0.6 × 10¹⁰ each 10 mg of tissue).Conclusions: For the first time, the quantitative evaluation of the αGal epitope in heart valve bioprostheses, already in clinical practice for about 40 yrs, was finally determined. Such quantification might provide indications of biocompatibility relevant for the selection of bioprosthetic devices and an increase in the confidence of the patient. It might become a major quality control tool in the production and redirection of future investigation in the quest for αGal‐free long‐lasting substitutes.

Bioprosthetic heart valves (BHVs) are commonly used to replace severely diseased heart valves but their susceptibility to structural valve degeneration (SVD) limits their use in young patients. We hypothesized that antibodies against immunogenic glycans present on BHVs, particularly antibodies against the xenoantigens galactose-α1,3-galactose (αGal) andN-glycolylneuraminic acid (Neu5Gc), could mediate their deterioration through calcification. We established a large longitudinal prospective international cohort of patients (n = 1668, 34 ± 43 months of follow-up (0.1–182); 4,998 blood samples) to investigate the hemodynamics and immune responses associated with BHVs up to 15 years after aortic valve replacement. Early signs of SVD appeared in <5% of BHV recipients within 2 years. The levels of both anti-αGal and anti-Neu5Gc IgGs significantly increased one month after BHV implantation. The levels of these IgGs declined thereafter but anti-αGal IgG levels declined significantly faster in control patients compared to BHV recipients. Neu5Gc, anti-Neu5Gc IgG and complement deposition were found in calcified BHVs at much higher levels than in calcified native aortic valves. Moreover, in mice, anti-Neu5Gc antibodies were unable to promote calcium deposition on subcutaneously implanted BHV tissue engineered to lack αGal and Neu5Gc antigens. These results indicate that BHVs manufactured using donor tissues deficient in αGal and Neu5Gc could be less prone to immune-mediated deterioration and have improved durability.

Transcatheter aortic valve implantation plays a leading role in the management of aortic stenosis in patients with comorbidities but no data are available about cardiac rehabilitation in these subjects. This study aimed to compare safety and efficacy of an early, exercise-based, cardiac rehabilitation programme in octogenarians after a traditional surgical aortic valve replacement versus transcatheter aortic valve implantation. Seventy-eight consecutive transcatheter aortic valve implantation patients were studied in order to evaluate the effect of an exercise-based cardiac rehabilitation programme in comparison to 80 of a similar age having surgical aortic valve replacement. Functional capacity was assessed by a 6 min walking test on admission and at the end of the programme. When possible, a cardiopulmonary exercise test was also performed before discharge. The two groups were similar in terms of gender and length of stay in cardiac rehabilitation; as expected, the transcatheter aortic valve implantation group had more comorbidities but no major complications occurred in either group during rehabilitation. All patients enhanced autonomy and mobility and were able to walk at least with the assistance of a stick. In those patients who were able to perform the 6 min walking test, the distance walked at discharge did not significantly differ between the groups (272.7 ± 108 vs. 294.2 ± 101 m, p = 0.42), neither did the exercise capacity assessed by cardiopulmonary exercise test (peak-VO₂ 12.5 ± 3.6 vs. 13.9 ± 2.7 ml/kg/min, p = 0.16). Cardiac rehabilitation is feasible, safe and effective in octogenarian patients after transcatheter aortic valve implantation as well as after traditional surgery. An early cardiac rehabilitation programme enhances independence, mobility and functional capacity and should be highly encouraged.