Searching for the optimal heart valve

In this issue of Biotechnology Journal, Weimer et al. [1] report an important and interesting study comparing human heart valve transplants (allo- or homografts) with xenogeneic valves for reconstruction of the right ventricular outflow tract in patients undergoing aortic valve replacement. Of particular importance, Weimar and colleagues focuses on younger patients (median age 42 and 47 years). The authors observe that immediately after implantation the hemodynamic characteristics were poorer in the xenograft group compared to the group with allografts. At one year post operation, the pressure gradients increased in both groups but were significantly higher in the xenografts. Degeneration occurred faster in the xenografts, and repeat surgery was necessary within 2 years in 12% of the patients. ...hemodynamic characteristics were poorer in the xenograft group compared to the group with allografts. Generally speaking, the average age of patients undergoing aortic valve replacement is 69 years [2] and the currently available biological valve substitutes (porcine or bovine) have a long-term function of 15-18 years. The majority of patients therefore, can be offered excellent valve substitutes; however younger patients (approximately 70 000 worldwide each year are younger than 60) need alternative options. Prosthetic valves have outstanding long-term results. These however, require life-long anticoagulation with potential for associated bleeding complications. In particular for young and physically active patients, this represents a substantial reduction in the quality of life. In addition, pediatric patients who need valve replacement pose serious challenges to surgeons. Biological valves degenerate in children dramatically faster (in less than 5 years) compared to adults. Prosthetic valves with a need for anticoagulation are also far from being optimal in the majority of active children. Allografts represent nearly perfect heart valve substitutes [3]. Allografts have optimal hemodynamic characteristics and are resistant to infections. Disadvantages of allografts, particularly in pediatric and young adult patients (the group presented by Weimar et al. [1]), include its limited availability (due to decreasing organ donations), an inability to grow, degeneration and subsequent long-term failure [4]. Potential culprits for long-term failure include immunological responses [5] and an increased calcium metabolism [6]. Despite these shortcomings, allografts remain the best valves for younger patients. The size specification of allografts in these young patients is at less than 23 mm. Due to the organ scarcity situation the availability for such small valves is extremely limited. Patients need to wait significantly longer for surgery (up to 6 months or longer). In cases of rapidly deteriorating conditions surgeons are forced to use alternative xenograft valves such as glutaraldehyde-fixed procine valves as that used by Weimar et al. [1]. The current results are alarming and indicate a strong need to refine and optimize biological valve substitutes for the growing young adolescent patient population. ...allografts are the best valves for younger patients but surgeons are forced to use xenografts in cases of emergency... There are currently two major research avenues pursued to overcome these limitations. The first one is the engineering of heart valves applying regenerative medicine principles. Following complex decellularization while maintaining the crucial extracellular matrix (ECM) integrity, the valves of porcine [7] or human origin [8] are implanted in children and young adults. Oversizing the valve at implant (diameter is larger than actually required) allows some enlargement. Real growth however requires viable tissue and consequently repopulation of the decellularized heart valves from the recipient's connecting tissue (outgrowths form anastomosis) or circulating cells. Despite this intriguing and charming idea there is so far no scientific evidence that this repopulation (shown only in animals) is actually working in humans. ...Weimar and colleagues are to be congratulated for highlighting the need to search for the optimal valve for young patients... Alternative research focuses on an optimization of long-term function of allografts to diminish degeneration and reduce the need for repeated surgery. Since 1968 standard frozen cryopreservation (SFC) has been employed, which includes valve storage in vapour-phase of liquid nitrogen [9]. Recent application of multiphoton imaging analysis (MIA) enabled for the first time detection of partial destruction of elastic and collagenous matrix in SFC valves [10]. This ECM destruction is postulated as freezing-induced ECM damage due to ice crystal formation. New cryopreservation techniques including vitrifictaion and ice-free cryopreservation promote glass formation instead of ice formation. As the preservation and warming are accomplished without any tissue destruction they enable exclusively complete preservation of ECM in heart valves [11]. There is substantiated hope that this will benefit patients in need of heart valve transplantation. Weimar and colleagues [1] are to be congratulated for their honest results highlighting the continuing limitations and need to search for the optimal valve for pediatric and young adult patients. Conflict of interest: The author declares no conflict of interest.