Analysis of prosthetic cardiac devices: a guide for the practising pathologist

Pathologists all over the world increasingly encounter prosthetic cardiac devices. A good evaluation of these devices is a valuable source of information, which can contribute to patient care and the appreciation and understanding of the pathobiology involved in the changes occurring between the host and the implanted prosthetic device. This article summarises the considerations underlying the analysis of prosthetic devices (particularly prosthetic heart valves), including the identification of the devices, the major morphological features of the devices, their modes of failure, and some technical details about evaluation and pitfalls.     

Bioprosthetic heart valves: modes of failure

Valve replacement started in 1960, with the surgeon now having a significant variety of prosthetic heart valves from which to choose. These valves are broadly divided into mechanical heart valves (MHV) and bioprosthetic heart valves (BHV). Improvements in the performance and ease of usage of BHV without the need for anticoagulant therapy are among the desired features of BHV and hence the increasingly preferred choice over their mechanical counterparts. However, with increased use the post-implantation complications have become more apparent, and these include: calcification, cusp tears, pannus growth, infective endocarditis, valve thrombosis and other factors specific to valve type. In this review we describe these complications in order to bring awareness among surgeons, clinicians and pathologists. Diagnosis, treatment and preventive measures, if taken in a timely manner, can help reduce their impact and further enhance the quality of life of patients with prosthetic heart valves.     

Flow in Prosthetic Heart Valves: State-of-the-Art and Future Directions

Since the first successful implantation of a prosthetic heart valve four decades ago, over 50 different designs have been developed including both mechanical and bioprosthetic valves. Today, the most widely implanted design is the mechanical bileaflet, with over 170,000 implants worldwide each year. Several different mechanical valves are currently available and many of them have good bulk forward flow hemodynamics, with lower transvalvular pressure drops, larger effective orifice areas, and fewer regions of forward flow stasis than their earlier-generation counterparts such as the ball-and-cage and tilting-disc valves. However, mechanical valve implants suffer from complications resulting from thrombus deposition and patients implanted with these valves need to be under long-term anti-coagulant therapy. In general, blood thinners are not needed with bioprosthetic implants, but tissue valves suffer from structural failure with, an average life-time of 10–12 years, before replacement is needed. Flow-induced stresses on the formed elements in blood have been implicated in thrombus initiation within the mechanical valve prostheses. Regions of stress concentration on the leaflets during the complex motion of the leaflets have been implicated with structural failure of the leaflets with bioprosthetic valves. In vivo and in vitro experimental studies have yielded valuable information on the relationship between hemodynamic stresses and the problems associated with the implants. More recently, Computational Fluid Dynamics (CFD) has emerged as a promising tool, which, alongside experimentation, can yield insights of unprecedented detail into the hemodynamics of prosthetic heart valves. For CFD to realize its full potential, however, it must rely on numerical techniques that can handle the enormous geometrical complexities of prosthetic devices with spatial and temporal resolution sufficiently high to accurately capture all hemodynamically relevant scales of motion. Such algorithms do not exist today and their development should be a major research priority. For CFD to further gain the confidence of valve designers and medical practitioners it must also undergo comprehensive validation with experimental data. Such validation requires the use of high-resolution flow measuring tools and techniques and the integration of experimental studies with CFD modeling.     

Artificial valves “up to date” in Japan

We have many choices when selecting artificial valves for valve replacement surgery. It is necessary to know the characteristics of the various prosthetic valves to make an appropriate decision for each valvular heart disease patient. In this review paper, we describe the features and benefits of the artificial valves available in Japan. Standard and new generation bioprostheses and mechanical prostheses are reviewed. The new technology of the catheter-delivery heart valve is also mentioned in this paper.     

DeBakey Surgitool mechanical heart valve prosthesis, explanted at 32 years

Contemporary mechanical heart value prostheses are expected to last "just about forever" or the patient's lifeline. They do however still suffer complications, some of which necessitate premature explantation. Complications today are mainly related to patient compliance with anticoagulant medication, infection and hemorrhage. The DeBakey Surgitool mechanical heart valve was the first such device to have Pyrolyte components. We present a DeBakey surgitool mechanical heart valve that was in place for 32 years! It was explanted for dysfunction related to tissue overgrowth and not to its related components. With good patient compliance, this mechanical heart valve prosthesis is an example of good prosthetic valve durability.     

Prosthetic heart valves: catering for the few

Prosthetic heart valves epitomize both the triumphant advance of cardiac surgery in its early days and its stagnation into a retrospective, exclusive first world discipline of late. Fifty-two years after the first diseased heart valve was replaced in a patient, prostheses largely represent the concepts of the 1960s with many of their design-inherent complications. While the sophisticated medical systems of the developed world may be able to cope with sub-optimal replacements, these valves are poorly suited to the developing world (where the overwhelming majority of potential valve recipients reside), due to differences in age profiles and socio-economic circumstances. Therefore, it is the latter group which suffered most from the sluggish pace of developments. While it previously took less than 7 years for mechanical heart valves to develop from the first commercially available ball-in-cage valve to the tilting pyrolytic-carbon disc valve, and another 10 years to arrive at the all-carbon bi-leaflet design, only small incremental improvements have been achieved since 1977. Similarly, bioprosthetic valves saw their last major break-through development in the late 1960s when formalin fixation was replaced by glutaraldehyde cross linking. Since then, poorly understood so-called 'anti-calcification' treatments were added and the homograft concept rediscovered under the catch-phrase 'stentless'. Still, tissue valves continue to degenerate fast in younger patients, making them unsuitable for developing countries. Yet, catheter-delivered prostheses almost exclusively use bioprosthetic tissue, thereby reducing one of the most promising developments for patients of the developing world into a fringe product for the few first world recipients. With tissue-engineered valves aiming at the narrow niche of congenital malformations and synthetic flexible leaflet valves being in their fifth decade of low-key development, heart valve prostheses seem to be destined to remain an unsatisfying and exclusive first world solution for a long time to come.     

Cardiovascular implant calcification: a survey and update.

Calcification of cardiovascular prosthetic implants is a common and important problem. This review provides an update based upon the Conference on Cardiovascular Implant Calcification held as part of the 13th World Congress of the International Society for Heart Research, 1989. A variety of cardiovascular prostheses are affected clinically by calcification, including bioprosthetic heart valves, aortic homografts and trileaflet polymeric valve prostheses. In addition, experimental studies have demonstrated calcification of artificial heart devices in ventricular assist systems in long-term calf studies. The pathophysiology of this disease process is incompletely understood. A common element between the various types of cardiovascular implant calcification is the localization of calcific deposits to devitalized cells and membranous debris. Prevention of cardiovascular implant calcification by either biomaterial modifications or regional drug therapy (controlled release) is being investigated.     

Air-flow resistances of silicone rubber voice prostheses after formation of bacterial and fungal biofilms.

Laryngectomized patients use silicone rubber voice prostheses to rehabilitate their voice. However, biofilm formation limits the lifetime of voice prostheses by causing leakage or an increased air-flow resistance and the prosthesis has to be replaced. To determine which bacterial or yeast strains, isolated from explanted voice prostheses, contribute most to increases in air-flow resistance of silicone rubber voice prostheses, biofilms consisting of either a bacterial or a yeast strain were grown on voice prostheses in the artificial throat model. The effects of these biofilms on air-flow resistances were determined by calculating the difference in air-flow resistance of the individual voice prosthesis as covered with a 7-day-old biofilm with the situation prior to biofilm formation. Conspicuously, voice prosthetic biofilms formed by the bacterial strains Staphylococcus aureus GB 2/1 and Rothia dentocariosa GBJ 41/25B and their excreted organic matter showed larger increases in air-flow resistance (more then 30 cm H(2)O.s/L) than biofilms formed by Candida species. This is contrary to the literature, where there seems to be agreement that Candida species are mainly responsible for clinical failure of silicone rubber voice prostheses.     

An analysis of autopsy findings in 108 patients who died after valve replacement

The pathological findings and the causes of death were reviewed in 108 patients who had received 142 heart valve prostheses (52 mechanical and 90 bioprostheses) at the National Cardiovascular Center in Osaka, Japan, from 1977 to 1991. Rheumatic heart disease was the major underlying disease (60.2%), and the age distribution at death ranged from 21 to 80-year-old. Survival duration after the surgery extended from 0 day to 9 years. Thirty-three patients (30.6%) died of perioperative complications such as myocardial haemorrhage and damage, or from heart failure which had been evident prior to the operation, a cause of death which predominated in patients who died within 1 week of surgery (15/17; 88.2%). Thirty-eight patients (35.2%) died of prostheses-related problems such as prosthetic valve failure (cuspal tears and calcifying destruction of the xenograft), thromboembolism, and prosthetic valve endocarditis. Endocarditis was frequent in patients who had survived longer than 1 year (25/33; 75.8%). None of the patients died of prostheses-related problems within 1 week. Non-infectious valve failure was more common in patients with bioprostheses than in those with mechanical valves; thromboembolism showed the opposite association. Prosthetic valve infective endocarditis was nearly equal in frequency in both types of valve.     

Beat to beat analysis of mechanical heart valves by means of return map

Three mechanical heart valves (two bileaflet prostheses and a tilting one) were investigated in a basic hardware setup in order to evaluate with a hydrophone their opening and closing action in time and in amplitude of each beat. The recorded signal was then segmented into the series of cycles xi(t) having a temporal duration equal to the working period imposed on the valve. Two return maps were defined, in order to evaluate the degree of dispersion of the resulting scatter plot: (i) the amplitude map xi(t) versus xi+1(t); (ii) the delay map for the closure of the valve within each beat versus the successive ones. To evaluate the results obtained, two indices were proposed based on both the degree of dispersion and the deviation of the regression line of the resulting scatter plot with respect to the bisector of the map plane. The tilting disc valve showed a lower degree of dispersion, both in the amplitude signal and in the closure time delays, with respect to the other two bileaflet heart valves. The methodology proposed here could be regarded as an alternative non-invasive tool to investigate the dynamic behaviour of prosthetic heart valves, especially in the case of their suspected failure.     

A 44-year experience of prosthetic heart valve implantation at Niigata University Hospital

Based on a single hospital experience of heart valve implantation from 1965 to 2009, the superiority of prosthetic heart valves including Starr-Edwards caged ball valves, Omniscience aortic tilting disc valves, and St. Jude Medical bileaflet valves are reviewed. This review discusses the prominent antithrombogenicity of the Starr-Edwards model 1200 aortic prosthesis under selected conditions, the relatively rarely thrombosed (despite its decreased opening angle) Omniscience aortic valve, the long-term outcomes 10 as well as 30 years after St. Jude Medical valve replacement, and finally the latest results on the significance of patient-aortic prosthesis mismatch in relation to myocardial hypertrophy. The findings described here should be considered in further investigations of cardiac valve prostheses.     

Autopsy-determined causes of death following heart valve replacement

The pathological findings and the principal cause of death were reviewed in 275 patients with 345 heart valve prostheses. Rheumatic fever necessitated valve replacement in 73% of these patients. Tissue valves bore significantly fewer and scantier thrombi than did the mechanical prostheses. Patients with these two groups of valves showed no significant difference with regard to the incidence of infarction of systemic organs. Patients with prostheses showed infarcts of the spleen, brain, and heart more often than did nonoperated controls with valvular disease. Among the mechanical valves, patients with Starr-Edwards valves showed the highest incidence of fatal thromboembolism. Prosthesis-related problems formed the biggest single cause of death in the 275 patients with valve prostheses. The mechanical valve group, which formed 82% of the total, had prosthesis-related problems as the prime cause of death; in the tissue valve group this complication ranked third in importance after unknown causes and diseases unrelated to valve surgery. Analysis of the valve-related causes of death showed that thrombosis and infection of the prosthesis were more important in the mechanical valves, whereas structural failure was more common with the tissue valves. Prosthesis-related fatal complications were present in 13% of the patients who died within 30 days postoperatively and in 61% of those who died later.     

Phonocardiogram spectral analysis simulator of mitral valve prostheses.

Spectral analysis of sounds produced in vitro by mitral valve prostheses placed in a specially designed flow simulator has been carried out using a short-time Fourier representation of the recorded signal. Time variations of power spectra are displayed as a three-dimensional plot. Sounds produced by three types of valves, namely ball and cage, tilting disk and porcine valves, were analysed. Each valve type produced a characteristic spectrogram, and, for a given valve, spectrograms were reproducible to within a margin of 5 dB. The simulator may be used to detect structural deficiencies and functional abnormalities of prosthetic heart valves. In addition to quantifying the noise level of mechanical valves, the system may be used for quality control purposes to identify faulty valves.     

Laser-doppler anemometer to study velocity fields in the vicinity of prosthetic heart valves

Laser-Doppler anemometry is relatively new technique which is used for measuring velocity fields. It has major applications in the field ofin vitro biofluid mechanics. The laser-Doppler anemometers have many advantages compared with the traditional hot-wire or hot-film anemometers which are still mainly used in studies of biofluid mechanics. A laser-Doppler anemometer (I.d.a) system which can be used to measurein vitro velocity and shear-stress profiles in the vicinity of prosthetic heart valves is described. Accurate velocity measurements in the vicinity of prosthetic heart valves are very scarce, and the use of I.d.a systems will facilitate acquisition of these data.     

Neuroplasticity in amputees: Main implications on bidirectional interfacing of cybernetic hand prostheses

The development of a new generation of hand prostheses that can ideally approximate the human ‘physiological’ performance in terms of movement dexterity and sensory feedback for amputees still poses many open research challenges. The most promising approaches aim at establishing a direct connection with either the central or the peripheral human nervous system by means of invasive or non-invasive neural interfaces. This paper starts from the assumption that a major contribution to derive functional and technical specifications for such interfaces, and even for the whole prosthetic system, can stem from in-depth analysis of the nervous system reorganization following limb amputation. Neuroplasticity can be modulated by the use of hand prostheses both in the acute phase and in the long-term. We hereby critically review the literature concerning neuroplastic phenomena in amputees, in terms of changes at different CNS levels, particularly for their implications on the development of bidirectional neural interfaces for cybernetic hand prostheses. Our analysis of the literature demonstrates that: (1) the level of CNS reorganization could be used as a parameter of the effectiveness achieved by the prosthetic device and its interfaces, in restoring the hand physiological functionality, (2) the prosthetic system could be seen as a neurorehabilitation tool, as it could induce reduction in aberrant plasticity and promote ‘good’ plasticity and (3) new generations of ‘natural’ interfaces can be developed by fully exploiting neuroplastic phenomena to restore neural connections originally governing the lost limb and linking them to the prosthetic system.     

Morphologic findings and causes of failure in 24 explanted Ionescu-Shiley low-profile pericardial heart valves.

From 1981 to 1987 just over 608 Ionescu-Shiley low-profile bovine pericardial bioprostheses were implanted at the Toronto Hospital. Twenty-four prostheses (11 aortic and 13 mitral) were surgically explanted from 1988 to 1990 from 20 adults (10 men and 10 women). Prosthesis failure was caused by primary tissue failure in 17 valves or by other mechanisms in seven valves. Variable degrees of tissue failure were also seen in four of the seven valves from the latter group. Primary tissue failure was characterized by fluid insudation between collagen bundles, para stent post tears (alignment stitch related, 20 valves), cusp perforation with prolapse, and calcification. The earliest cusp tears occurred at 28 months. Calcification (10 of 24 cases) was minimal in seven of 10 valves (occurring primarily at the margins of the torn cusp), moderate in two, and severe in one. Tissue overgrowth (pannus) was seen in all but three prostheses. Like its predecessor, the Ionescu-Shiley standard pericardial valve, this prosthesis failed at 2 to 5 years largely due to design-related (alignment stitch) causes and tissue degeneration. Calcification was less prominent, while tissue overgrowth (pannus) was more marked.     

Pathology in patients with ventricular assist devices: a study of 21 autopsies, 24 ventricular apical core biopsies and 24 explanted hearts.

BACKGROUND: Ventricular assist devices (VADs) are used as a bridge to cardiac transplantation or as a permanent or sometimes temporary treatment for end stage heart failure. METHODS: Our autopsy and surgical pathology experience with VADs prior to August 2002 was reviewed. Noted were patient's age, sex, underlying (UCOD) and proximate causes of death (PCOD), duration of VAD implantation, presence of native or prosthetic valvar disease and organ complications. Myocardium from biopsies and explanted hearts were blindly assessed for coagulative necrosis (CN), contraction bands (CB), myocytolysis (MC), increased eosinophilia (IE), myocyte waviness (MW) and fibrosis (F). Each was graded as either mild (score 1), moderate (score 2) or severe (score 3). RESULTS: Autopsy patients: Twenty-one patients, with mean age 55 years (range 10-73), comprised 10 women and 11 men. UCOD was ischemic disease in 16 patients, dilated cardiomyopathy in 4 and aortic valve disease in 1. The mean duration of VAD implantation was 125.7 days (range 1-1095 days, S.D.=253.6). Five patients had biventricular VADs, and 16 had LVAD only. Acquired aortic valve fusion was noted in three patients. PCOD was VAD related in six, donor heart problem in four, cerebrovascular accident in four, miscellaneous in three, pulmonary hypertension in two and aortic disease in two patients. Morbidity: local liver necrosis in seven, acquired aortic valve disease in four, gut infarction in three, abdominal aortic aneurysm in two and host cell assault against VAD porcine aortic valves in one case. Biopsies and explanted hearts: Twenty-four patients had a mean age of 53 years (range 38-68, S.D.=8.6). VADs were implanted for 177.8 days (range 7-593 days, S.D.=151.1). Comparison of histologic scores of biopsies with explanted hearts showed the following: CN 1.33 (S.D.=1.4)/0.21 (S.D.=0.66; P<.001); CB: 2.1 (S.D.=0.93)/0.83 (S.D.=0.28; NS); MC: 0.88 (S.D.=1.19)/0.13 (S.D.=0.34; P<.01); IE: 1.71 (S.D.=1.27)/0.38 (S.D.=0.65; NS); fibrosis: 1.08 (S.D.=1.35)/1.75 (S.D.=1.26; NS); and MW: 1.50 (S.D.=1.22)/0.59 (S.D.=0.73; P<.01). Acquired aortic stenosis developed in six hearts, and one heart showed thrombotic occlusion of the left ventricular outflow tract below an aortic bioprosthesis. CONCLUSIONS: VAD significantly reduced the amount of CN, MC and MW in the left ventricle but may lead to acquired aortic stenosis of native aortic valves or total occlusive thrombosis of aortic prosthetic valves. Proximate cause of death was, most often, VAD related.     

Beat to beat analysis of mechanical heart valves by means of return map

Three mechanical heart valves (two bileaflet prostheses and a tilting one) were investigated in a basic hardware setup in order to evaluate with a hydrophone their opening and closing action in time and in amplitude of each beat. The recorded signal was then segmented into the series of cycles x_i(t) having a temporal duration equal to the working period imposed on the valve. Two return maps were defined, in order to evaluate the degree of dispersion of the resulting scatter plot: (i) the amplitude map x_i(t) versus x_i+1(t); (ii) the delay map for the closure of the valve within each beat versus the successive ones. To evaluate the results obtained, two indices were proposed based on both the degree of dispersion and the deviation of the regression line of the resulting scatter plot with respect to the bisector of the map plane. The tilting disc valve showed a lower degree of dispersion, both in the amplitude signal and in the closure time delays, with respect to the other two bileaflet heart valves. The methodology proposed here could be regarded as an alternative non-invasive tool to investigate the dynamic behaviour of prosthetic heart valves, especially in the case of their suspected failure.