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Impact of prosthesis-patient mismatch on hemodynamic and symptomatic status, morbidity and mortality after aortic valve replacement with a bioprosthetic heart valve.

BACKGROUND AND AIMS OF THE STUDY: Previous studies have shown that the effective orifice area of an aortic prosthetic valve may be too small in relation to the patient's body surface area, resulting in abnormally high gradients. The consequences of this condition, termed prosthesis-patient mismatch, have not been fully studied. The study objective was to determine if the condition has a detrimental effect on symptomatic and hemodynamic status, morbidity and mortality of patients undergoing aortic valve replacement. METHODS: A cohort of 392 patients was prospectively followed for up to seven years after implantation of a Medtronic Intact bioprosthesis. Doppler echocardiography was performed annually in 72 patients. Based on previous studies, presence of mismatch was defined as an indexed valve area < or = 0.85 cm2/m2. RESULTS: Mismatch was associated with less postoperative improvement of NYHA functional class (p < 0.009) independently of other predictors, such as age and preoperative functional class, but had no significant impact on patient survival (mismatch: 75 +/- 4%, no mismatch: 79 +/- 3%; p = 0.59) and valve-related morbidity up to seven years. Cardiac index was similar in patients with and without mismatch up to three years after operation but decreased significantly thereafter only in patients with mismatch (-0.54 +/- 0.32 versus -0.17 +/- 0.49 l/min/m2; p = 0.04). Likewise, the mean transprosthetic gradient, which was higher at one year after operation in patients with mismatch (22 +/- 8 versus 15 +/- 7 mmHg), increased significantly (+6 +/- 6 versus +1 +/- 1 mmHg; p = 0.008) only in this group during follow up. CONCLUSIONS: Patients with mismatch have less symptomatic improvement and worse hemodynamics that continue to deteriorate with time. However, medium-term prognosis (up to seven years) is relatively good. Further studies are necessary to determine the longer-term effects of mismatch on morbidity and mortality.

Aged↗

Evaluation of biodegradable, three-dimensional matrices for tissue engineering of heart valves.

A crucial factor in tissue engineering of heart valves is the type of scaffold material. In the following study, we tested three different biodegradable scaffold materials, polyglycolic acid (PGA), polyhydroxyalkanoate (PHA), and poly-4-hydroxybutyrate (P4HB), as scaffolds for tissue engineering of heart valves. We modified PHA and P4HB by a salt leaching technique to create a porous matrix. We constructed trileaflet heart valve scaffolds from each polymer and tested them in a pulsatile flow bioreactor. In addition, we evaluated the cell attachment to our polymers by creating four tubes of each material (length equals 4 cm; inner diameter, 0.5 cm), seeding each sample with 8,000,000 ovine vascular cells, and incubating the cell-polymer construct for 8 days (37 degrees C and 5% CO2). The seeded vascular constructs were exposed to continuous flow for 1 hour. Analysis of samples included DNA assay before and after flow exposure, 4-hydroxyproline assay, and environmental scanning electron microscopy (ESEM). We fabricated trileaflet heart valve scaffolds from porous PHA and porous P4HB, which opened and closed synchronously in a pulsatile bioreactor. It was not possible to create a functional trileaflet heart valve scaffold from PGA. After seeding and incubating the PGA-, PHA-, and P4HB-tubes, there were significantly (p < 0.001) more cells on PGA compared with PHA and P4HB. There were no significant differences among the materials after flow exposure, but there was a significantly higher collagen content (p < 0.017) on the PGA samples compared with P4HB and PHA. Cell attachment and collagen content was significantly higher on PGA samples compared with PHA and P4HB. However, PHA and P4HB also demonstrate a considerable amount of cell attachment and collagen development and share the major advantage that both materials are thermoplastic, making it possible to mold them into the shape of a functional scaffold for tissue engineering of heart valves.

Animals↗

Tissue engineering of cardiac valve prostheses II: biomechanical characterization of decellularized porcine aortic heart valves.

BACKGROUND AND AIMS OF THE STUDY: For both young patients with congenital heart disease and young, growing adults there is a need for replacement heart valves that will develop with the patient. Tissue-engineered heart valves coupled with in-vitro recellularization have this potential. One approach is to use acellular tissue matrices, but the decellularization treatment must not affect the biomechanical integrity of the valvular matrix. This study investigated the effect of 0.03% (w/v) and 0.1% (w/v) sodium dodecyl sulfate (SDS) on the mechanical integrity of porcine aortic valve leaflets. METHODS: Left coronary porcine leaflets were treated with SDS (0.03% or 0.1%, w/v) in hypotonic or isotonic buffer and buffer alone. SDS in hypotonic buffer produced accellularity. Circumferential and radial specimens of treated leaflets were subjected to uniaxial tensile testing, and the effect of the buffer on leaflet morphology was assessed. Whole porcine aortic roots were also treated with 0.1% (w/v) SDS and subjected to function testing. RESULTS: SDS treatment significantly increased extensibility of the leaflet specimens, which was greater in the circumferential than radial direction. This was seen as a significantly decreased slope of both the elastic and collagen phases of the stress-strain behavior. The ultimate tensile strength and transition stress were not affected significantly; nor was there any significant difference between hypotonic buffer and hypotonic buffer + SDS treatments. Study of the leaflet morphology suggested that the increased extensibility was due to shrinkage as well as to increased hydration of the treated leaflets caused by the hypotonic buffer. CONCLUSION: SDS treatment produced a more extensible tissue with equal strength compared with the fresh aortic valve. Functionality experiments with SDS-treated whole aortic roots showed complete valve leaflet competence under physiological pressures (120 mmHg) as well as physiological leaflet kinematics.

Animals↗

The effect of varying degrees of stenosis on the characteristics of turbulent pulsatile flow through heart valves.

Many problems and complications associated with heart valves are related to the dynamic behavior of the valve and the resultant unsteady flow patterns. An accurate depiction of the spatial and temporal velocity and rms distributions imparts better understanding of flow related valve complications, and may be used as a guideline in valve design. While the generalized correlation between increased turbulence level and the severity of the stenosis is well established, few studies addressed the issue of the intermittent nature of turbulence and its timing in the cardiac cycle, and almost none assessed the effect of a progressive stenosis on the flow characteristics through heart valves. In this experimental work we simulated the type of flow which is present in normal and stenosed valves and conducted a comprehensive investigation of valve hemodynamics, valvular turbulence and morphology under varying degrees of stenosis. The characteristics of valves and stenoses were simulated closely, to achieve the flow conditions that initiate turbulent flow conditions. Laser Doppler anemometry (LDA) measurements were carried out in a pulse duplicator system distal to trileaflet polyurethane prosthetic heart valves, installed at mitral and aortic positions. The effect of the degree of the stenosis was comparatively studied through the structure of the turbulent jets emerging from normal and stenotic heart valves. Maximum turbulence level was achieved during the decelerating phase and correlated to the severity of the stenosis, followed by relaminarization of the flow during the acceleration phase. The intermittent nature of the turbulence emphasized the importance of realizing the timing of the turbulence production and its spatial location for optimizing current valve designs. The plug flow through the normal aortic valve prosthesis was replaced by jet like behavior for a 65% stenosis, with the jet becoming narrower and stronger for a 90% stenosis. The morphology of the velocity and turbulence waveforms was found to be governed by the stenosis geometry and the valve position (aortic, mitral).

Aortic Valve↗

Comparison of different decellularization procedures of porcine heart valves.

BACKGROUND: Tissue engineering of heart valves should avoid the disadvantages of conventional prostheses. In this study we tested different decellularization procedures for their potential of cell removal and their ability to preserve the matrix. METHODS: Specimens of porcine aortic and pulmonary roots were treated with either trypsin or sodium-dodecyl-sulfate (SDS) or Triton-X 100 and sodium-deoxycholate with a range of concentrations. Tissue samples were then processed for scanning electron microscopy and laser scanning microscopy. RESULTS: Trypsin achieved only incomplete decellularization and caused severe structural alterations of the matrix. In contrast SDS removed cells completely but caused strong structural alterations. Treatment with Triton-X100 and sodium-deoxycholate achieved both complete decellularization and preservation of the matrix structure. CONCLUSION: Techniques of decellularization are highly variable in efficiency and matrix preservation and was best achieved in our study with Triton-X100 and sodium deoxycholate.

Animals↗

A profile of valve replacement surgery in the UK (1986-1997): a study from the UK Heart Valve Registry.

BACKGROUND AND AIM OF THE STUDY: Approximately 150,000 heart valves are implanted annually world-wide, of which 4% are implanted in the UK. We present a comprehensive profile of the trends in valve replacement (VR) surgery in the UK since 1986 based on data from the UK Heart Valve Registry (UKHVR). METHODOLOGY: The UKHVR is a computerized database collecting prospective data on VR surgery in all UK cardiac units. All patients are tracked by national agencies who register all deaths of UK residents. Thus, the Registry receives a copy of each patient's death certificate and enters the date, place and certified cause(s) of death on the database. RESULTS: Between January 1st 1986 and December 31st 1997, a total of 58,195 patients underwent first-time VR surgery and received 63,649 valves. Mean age at operation in 1986 was 58.7 years (range: 18-87 years) and this rose to 64.7 years (range: 18-94 years) in 1997. In 1986, 12% (n = 578) of patients who underwent VR surgery were aged >70 years compared with 36% (n = 5125) in 1997. There was a 4% decrease in double VR surgery and a 15% reduction in mitral VR between 1986 and 1997. The majority of patients received a mechanical valve; within this group the number of bileaflet valve implants increased significantly since 1986. There has been a reversal in the downward trend in pericardial valves implanted since 1993. Follow up was 96.1% complete, with a total of 342,993 patient-years. Mortality (30-day) fell from 6.9% in 1986 to 3.8% in 1995, but increased to 6.7% in the two years to 1997. Actuarial survival at 1, 5 and 10 years was 89.5%, 78.5% and 61.8%, respectively; confidence intervals of 0.5% reflect the enormity of the database and quality of the data. CONCLUSIONS: UKHVR data can provide comprehensive year-by-year and trend analyses in a database in excess of 63,000 valves. Changes in patient demographics, choice of implanted valve and the pattern of heart valve disease are evident within the UK over the past 11 years.

Adolescent↗

Expression of 5-hydroxytryptamine receptor subtype messenger RNA in interstitial cells from human heart valves.

BACKGROUND AND AIM OF THE STUDY: Severe heart valve disorder has been reported in patients receiving a combination of the anorectic drugs fenfluramine and phentermine. The exact molecular mechanisms involved remain unknown. Fenfluramine alters the serotonin level in the brain, while phentermine interferes with the pulmonary clearance of serotonin; these data suggest that serotonin levels affect regulation of valve function. The aim of the present study was to characterize the serotonin receptor (5-hydroxytryptamine) subtypes expressed in the interstitial cells of human heart valves. METHODS: Interstitial cells were isolated and cultured from the aortic, pulmonary, mitral and tricuspid valves of recipient hearts obtained during transplantation. Total RNA was extracted from cultured cells in order to determine gene expression by reverse transcription-polymerase chain reaction (RT-PCR) using 5-hydroxytryptamine (5-HT) subtype-specific primer pairs. RESULTS: The results show that: (i) 5-HT 1B and 1D receptor subtypes are expressed in all four heart valves. This is significant as the 1B and 1D receptor subfamilies are the target of the anti-migraine drug sumatriptan, and these receptors regulate cardiac function and movement; (ii) 5-HT 1A, 5-HT 1E and 5-HT 1F are not expressed in interstitial cells isolated from the valves. CONCLUSION: We conclude that preliminary evidence exists for the presence of distinct subsets of 5-HT receptors in human heart valves, indicating that interstitial cells of the valves potentially respond to serotonin levels.

Appetite Depressants↗

Return to work after heart valve replacement.

One hundred patients who underwent heart valve replacement during the years 1977 to 1985 were reviewed an average of 57 months after surgery. The overall rate of reemployment after the operation was 78%. The most important factors influencing the return to work were the employment status before surgery, age at the time of surgery, the number and site of the diseased valve, the preoperative New York Heart Association (NYHA) functional class and the number of times cardiac surgery was performed. These factors were closely related to the optimal timing of heart valve replacement. It was suggested that the rate of return to work and the quality of life would be improved if the heart valve replacement had been performed at an earlier stage of the disease.

Adolescent↗

Innovative developments of the heart valves designed for use in ventricular assist devices.

Prosthetic heart valves are routinely used for replacing diseased natural heart valves. Even today, after five decades of prosthetic heart valve development, in the authors opinion the main problem associated with these valves is the risk of thromboembolic complications caused by unnatural hemodynamics. Further growing application of prosthetic heart valves is their use in the pulsatile ventricular assist devices (VADs). VADs may provide life-saving solutions to patients with severe cardiovascular diseases and are superior to drug therapy for patients with severe heart failure. However, the clinical applications of VADs still suffer from thromboembolic complications due to thrombus formations in the vicinity of the valves. Wherever the flow is stagnant or flow separation occurs, a thrombus is likely to form. The design of the heart valves with flow avoiding the formation of stagnant zones is one of the main goals in the development of new valves. This article reviews some innovative design approaches of the valves specially designed for use in VADs. Three design concepts are presented; one is based on the tilting disk valve, the second on the natural valve geometry and the third on the ball valve principle. However, these three different concepts have one common basic idea; the use of the freedom of the valve-housing design. This additional design freedom, which is available in VADs, is a key factor in the development of new valves with optimal hemodynamic performance.

Computer Simulation↗

Tissue engineering of autologous human heart valves using cryopreserved vascular umbilical cord cells.

BACKGROUND: Tissue engineering of autologous heart valves with the potential to grow and to remodel represents a promising concept in pediatric cardiovascular surgery. Currently we are exploring the impact of cryopreserved human umbilical cord cells (CHUCCs) for the fabrication of tissue-engineered heart valves for patients diagnosed prenatally with congenital heart lesions, potentially enabling heart valve replacement in the early years of life. METHODS: Human umbilical cord cells were isolated from vascular segments of umbilical cords and cryopreserved in a cell bank. After 12 weeks the cryopreserved cells were again expanded in culture and characterized by histology, immunohistochemistry, and proliferation assays. Trileaflet heart valve scaffolds were fabricated from a porous polymer (P4HB, Tepha Inc, Cambridge, MA) and sequentially seeded with CHUCCs (n = 10). Five of the heart valve constructs were grown for 7 days in a pulse duplicator and, as a control, five constructs were grown under static cell culture conditions for 7 days. Analysis of all tissue-engineered heart valves included histology, immunohistochemistry, electron microscopy, functional analysis, and biomechanical and biochemical examination. RESULTS: We found that CHUCCs remained viable after 12 weeks of cryopreservation and showed a myofibroblast-like morphology that stained positive for alpha-actin and fibroblast specific marker. Histology of the tissue-engineered heart valves showed layered tissue formation, including connective tissue between the inside and the outside of the porous scaffold. Immunohistochemistry was positive for collagen (types I, III, and IV), desmin, laminin, and alpha-actin. Electron microscopy showed that the cells had grown into the pores and formed a confluent tissue layer during maturation in the pulsatile flow system. Biochemical examination showed an increase of extracellular matrix formation in constructs after pulsatile flow exposure compared with the static control group. Functional analysis demonstrated a physiological increase of the intracellular Ca2+ concentration of the recultivated cells and the conditioned constructs after stimulation with histamine. CONCLUSIONS: This study demonstrates in vitro generation of viable and functional human heart valves based on CHUCCs and biomimetic flow culture systems. The CHUCCs demonstrated excellent growth potential and abilities of in vitro tissue formation. These findings suggest the potential benefit of establishing autologous human cell banks for pediatric patients diagnosed intrauterinely with congenital defects that will potentially require heart valve replacement in the early years of life.

Actins↗

Comparative study of cellular and extracellular matrix composition of native and tissue engineered heart valves.

Tissue engineering of heart valves utilizes biodegradable or metabolizable scaffolds for remodeling by seeded autologous cells. The aim of this study was to determine and compare extracellular matrix (ECM) formations, cellular phenotypes and cell location of native and tissue engineered (TE) valve leaflets. Ovine carotid arteries, ovine and porcine hearts were obtained from slaughterhouses. Cells were isolated from carotid arteries and dissected ovine, porcine and TE leaflets. TE constructs were fabricated from decellularized porcine pulmonary valves, seeded ovine arterial cells and subsequent 16 days dynamic in vitro culture using a pulsatile bioreactor. Native and TE valves were studied by histology (hematoxylin-eosin, resorcin-fuchsin, Movat pentachrome), NIR femtosecond multiphoton laser scanning microscopy and scanning electron microscopy (SEM). Cells of native and TE tissues were identified and localized by immunohistochemistry. Arterial, valvular and re-isolated TE-construct cells were processed for immunocytochemistry and Western blotting. ECM analysis and SEM revealed characteristical and comparable structures in native and TE leaflets. Most cells in native leaflets stained strongly positive for vimentin. Cells positive to alpha-smooth muscle actin (alpha-SMA), myosin and calponin were only found at the ventricular (inflow) side of ovine aortic and porcine pulmonary valve leaflets. Cells from TE constructs had a strong expression of vimentin, alpha-SMA, myosin, calponin and h-caldesmon throughout the entire leaflet. Comparable ECM formation and endothelial cell lining of native and TE leaflets could be demonstrated. However, immunostaining revealed significant differences between valvular cell phenotypes of native and TE leaflets. These results may be essential for further cardiovascular tissue engineering efforts.

Animals↗

[Improvement of cardiac function by aortic valve replacement for chronic aortic regurgitation with carbomedics heart valve].

Cardiac function after aortic valve replacement for chronic aortic regurgitation with CarboMedics heart valve was evaluated repeatedly by echocardiography and some examinations in 27 cases. There was no late death and all patients belonged to NYHA I functional class postoperatively. Systolic and diastolic dimensions of left ventricle, left ventricular mass index, cardiothoracic ratio and SV1+RV5 on electrocardiography improved significantly within half a year and those improved results remained thereafter. Fractional shortening of left ventricle also improved gradually and the difference reached statistical significance one year later. This investigation revealed reduced systolic function or eccentric myocardial hypertrophy were often reversible. Average values of systolic diameter and fractional shortening late after operation were within normal range even in cases whose preoperative systolic function were severely depressed. Left ventricular mass index decreased markedly although postoperative values were still out of normal range in most cases. These results suggest that aortic valve replacement can be indicated even in cases of aortic regurgitation with severely impaired preoperative cardiac function.

Adolescent↗

Cardiac catabolic factors: the degradation of heart valve intercellular matrix.

Cultures of porcine heart valves and aorta secrete a factor that stimulates the degradation of cartilage matrix in a fashion similar to that displayed by synovial catabolin. The heart valve factor also induces the release of chondroitin sulfate and hydroxyproline from isolated heart valve cultures. The present observations support the hypothesis that tissues producing catabolic factors (catabolins) may well be responsive to them and that these messengers may play a role in the cellular regulation of the degradation of intercellular macromolecules.

Animals↗

Flexible bioprosthetic pericardial heart valve.

A flexible bioprosthetic pericardial heart valve has been produced as a consequence of adverse long-term clinical information about tissue heart valves on rigid frames. The concept of flexibility has been supported by a comparison between homograft valves on rigid and flexible supports used in the mitral position. Principles and methods of construction of this flexible valve are described and it is intended that this inexpensive plastic frame will provide support for a bioprosthesis which will be a useful addition to choices for cardiac valve replacements.

Acetals↗

Living artificial heart valve alternatives: a review.

Conventional replacement therapies for heart valve disease are associated with significant drawbacks. The field of tissue engineering has emerged as an exciting alternative in the search for improved heart valve replacement structures. One of the principles behind this concept is the transplantation of living elements, embedded in a suitable scaffold material, to the diseased site where the structure becomes integrated with patients' tissue to restore natural function. Significant progress has been made in the last ten years in the development of a living artificial heart valve alternative (LAHVA), with the identification of potential replacement sources for valve cells, scaffolds to maintain the cells in a three-dimensional environment, and signals to promote tissue development. This review addresses the need for a tissue-engineered alternative to current prostheses and provides a detailed account of normal heart valve structure--the blueprint for LAHVA fabrication. The research efforts to create a viable LAHVA, including recent developments, are discussed. Particular attention is focused on the choice of cell source for LAHVA construction, the use of biodegradable natural and synthetic polymeric scaffolds as extracellular matrix derivatives, and exogenous stimulation of tissue growth. The critical challenges involved in LAHVA development and possible future areas of investigation are also discussed.

Absorbable Implants↗

Non-destructive evaluation of prosthetic heart valves by holographic interferometry.

Dysfunction of prosthetic heart valves is a common complication after heart valve replacement, affecting both biologic and mechanical prostheses. A preoperative, non-destructive test of each individual valve may help to prevent the implantation of a valve which has material weaknesses. To this end we developed a technique for testing heart valve prostheses by holographic interferometry. The advantage of this technique is that it provides a non-contact, non-destructive, highly sensitive three dimensional analysis of the valve under loading. Samples of several mechanical and biologic valve substitutes were investigated. Deformations of the valve, due to small pressure differences applied to the samples in a specially developed test chamber, were recorded by double exposure holography. A fringe pattern superimposed on the image of the valve reconstructed from the hologram clearly indicates the presence of even the slightest defect in the valve material. Our experimental results demonstrate the ability of non-destructive holographic screening testing to detect defects or weaknesses which may potentially lead to dysfunction in replacement valves.

Animals↗

Mechanisms of mechanical heart valve cavitation in an electrohydraulic total artificial heart.

Until now, we have estimated cavitation for mechanical heart valves (MHV) mounted in an electrohydraulic total artificial heart (EHTAH) with tap water as a working fluid. However, tap water at room temperature is not a proper substitute for blood at 37 degrees C. We therefore investigated MHV cavitation using a glycerin solution that was identical in viscosity and vapor pressure to blood at body temperature. In this study, six different kinds of monoleaflet and bileaflet valves were mounted in the mitral position in an EHTAH, and we investigated the mechanisms for MHV cavitation. The valve closing velocity, pressure drop measurements, and a high-speed video camera were used to investigate the mechanism for MHV cavitation and to select the best MHV for our EHTAH. The closing velocity of the bileaflet valves was slower than that of the monoleaflet valves. Cavitation bubbles were concentrated on the edge of the valve stop and along the leaflet tip. It was established that squeeze flow holds the key to MHV cavitation in our study. Cavitation intensity increased with an increase in the valve closing velocity and the valve stop area. With regard to squeeze flow, the Björk-Shiley valve, because it is associated with slow squeeze flow, and the bileaflet valve with low valve closing velocity and small valve stop areas are better able to prevent blood cell damage than the monoleaflet valves.

Heart Valve Prosthesis↗