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[Biopsy of the heart valves. 872 cases].

In this study, 872 heart valves surgically excised from 810 patients during a period of 5 years (1994 through 1998) were examined pathologically. There was a predominance of aortic (506 patients) versus mitral valves (246 pts.). While aortic valves came more often from men (364) than from women (142), in mitral valves the M:F ratio is 82/164. Isolated calcific aortic stenosis appeared as the most frequent valvular disease (418 pts.), with predominance of its sclerotic-senile type (238 pts.). Mitral stenosis (185 pts.) remains the classical post-rheumatic disease. The relative frequency of a subvalvular stenosing mitral lesion is stressed. The "pure" incompetence of both aortic (70 pts.) and mitral (56 pts.) valve was usually based on valvular myxoid degeneration. An aorto-mitral disease requiring replacement of both valves (51 pts.) presented typically as a post-rheumatic lesion, however, a combination of a post-rheumatic mitral with a degenerative-sclerotic aortic valve disease may be possible. In 30 patients, the valvular replacement was performed for infective endocarditis or a post-IE lesion, mostly of the aortic valve. With the almost non-existence of acute rheumatic fever and with the increasing average age of population in this country, we may expect a long-term decline in mitral valve disease and an increase in aortic valve disease, particularly in the sclerotic type of aortic stenosis.

Adult↗

Low-molecular-weight heparin for the treatment of patients with mechanical heart valves.

BACKGROUND: The interruption of oral anticoagulant (OAC) administration is sometimes indicated in patients with mechanical heart valves, mainly before noncardiac surgery, non-surgical interventions, and pregnancy. Unfractionated heparin (UH) is currently the substitute for selected patients. Low-molecular-weight heparin (LMWH) offers theoretical advantages over UH, but is not currently considered in clinical guidelines as an alternative to UH in patients with prosthetic valves. HYPOTHESIS: The aim of the present study was to review the data accumulated so far on the use of LMWH in this patient population and to discuss its applicability in common practice. METHODS: For this paper, the current medical literature on LMWH in patients with mechanical heart valves was extensively reviewed. RESULTS: There were eight series and six case reports. None of the studies was randomized, and only one was prospective. Data to establish the thromboembolic risk were incomplete. After excluding case reports, the following groups were constructed: (a) short-term administration, after valve insertion (n = 212); (b) short-term, perioperative (noncardiac)/periprocedural (n = 114); (c) long-term, due to intolerance to OAC (n = 16); (d) long-term, in pregnancy (n = 10). The incidence rate of thromboembolism was 0.9% for all the studies and 0.5, 0, 20, and 0% in groups a, b, c, and d, respectively; for hemorrhage, the overall rate was 3.4% (3.8, 2.6, 10, and 0% for the respective groups). CONCLUSIONS: In patients with mechanical heart valves, short-term LMWH therapy compares favorably with UH. Data on mid- and long-term LMWH administration in these patients are sparse. Further randomized studies are needed to confirm the safety and precise indications for the use of LMWH in patients with mechanical heart valves.

Anticoagulants↗

A microcomputer-based data acquisition system for a prosthetic heart valve test apparatus.

The hydrodynamic testing of prosthetic heart valves in the laboratory under pulsatile flow conditions remains the only way of obtaining detailed information about valve function. Test procedures have become increasingly sophisticated, with a variety of different test conditions and detailed analysis of the pressure and flow signals. A computerized data acquisition system has been developed for use with the Glasgow pulsatile flow test apparatus. The computer collects seven signals from the test rig over a period of 20 s, and calculates the average waveform for each signal. Standard parameters, such as mean pressure differences, mean flows, regurgitant volumes and energy losses, are calculated automatically. The complexity of the analysis and the need for standardized documentation makes computerization essential. The system has been used extensively for function tests on over 160 prosthetic heart valves.

Biomedical Engineering↗

Surface modification of polyurethane heart valves: effects on fatigue life and calcification.

Polyurethane heart valves can be functionally durable with minimal calcification, in vitro. In vivo, these characteristics will depend on the resistance of the polyurethane to thrombogenesis and biodegradation. Surface modification may improve the polyurethane in these respects, but may adversely affect calcification and durability. This study investigates the effects of surface modifications of two polyurethane heart valves (PEU and PEUE) on their in vitro fatigue and calcification behaviour. Modifications included heparin, taurine, 3-aminopropyltriethoxysilane and polyethylene oxide (PEO). Neither hydrodynamic function nor leaflet thickness distribution was significantly altered by surface modification. PEO-modification was detrimental to valve fatigue durability and calcification. Heparin, taurine or aminosilane modifications of PEU valves increased durability. Aminosilane modification of PEUE valves increased durability compared with PEO modification. Appropriate surface modification may be useful to improve blood compatibility of implantable polyurethanes, and may also be advantageous as regards fatigue durability of flexing materials in longterm applications.

Analysis of Variance↗

Tissue-engineered heart valve leaflets: an effective method of obtaining acellularized valve xenografts.

UNLABELLED: To determine the most effective method of producing the acellularized xenograft heart valve leaflets, we compared pathological findings of the xenograft heart valve leaflets produced by three methods; freeze-thawing, Triton and NaCl-SDS treatment and further analyzed the pattern of endothelial cells seeded onto them. MATERIALS AND METHODS: Two pigs were sacrificed and three pulmonary valve leaflets were harvested from each animal. They were immediately stored in a tissue preservation solution and assigned in one of the three preparation methods for acellularization. Endothelial cells from the jugular vein of a goat were isolated and seeded onto the acellularized xenograft heart valve leaflets. Light and Electron microscopic analyses were performed. RESULT AND CONCLUSION: H & E stain showed that cells were almost absent in the leaflet treated with NaCl-SDS, while cells were partly present in the leaflets treated, one with Triton and the other Freeze-thawing. Transmission microscopic analyses showed cell-free matrix with well preserved collagen architecture under the seeded endothelial cells in the leaflets treated with NaCl-SDS. In conclusion, the valve leaflets treated with NaCl-SDS among three representative methods of acellularization of tissues (freeze-thawing, Triton X-100, and NaCl-SDS) showed the better results than the others in terms of the efficacy of decellularization and response to endothelial cell seeding.

Animals↗

Early investigation of silver-coated Silzone heart valves prosthesis in 126 patients.

BACKGROUND AND AIM OF THE STUDY: Permanent silver (Silzone) coating of the sewing cuff of St. Jude Medical prosthetic heart valves may reduce the rate of prosthetic valve endocarditis (PVE). However, the incidence of paravalvular leaks and stroke in patients after implantation of Silzone-coated heart valve prostheses is largely unknown. METHODS: Complications were analyzed among 126 consecutive patients (78 males, 48 females; mean age 64.7 years; range: 40-80 years) who received Silzone-coated prostheses at our institution between February 1998 and December 1999. Among patients, 94 had aortic valve replacement, 29 mitral valve replacement, and three had aortic and mitral valve replacement. Concomitant cardiac procedures (mainly coronary bypass) were performed in 47 patients (37.3%). RESULTS: Hospital mortality was 1.6% (2/126) and freedom from valve-related mortality 99.2+/-0.9%. Total follow up was 137.4 patient-years, and 98.4% complete. Strokes or transitory ischemic attacks (TIAs) occurred in four cases (two strokes, two TIAs; stroke rate 1.5%/year; 95% CI 0.4-2.6%/year; stroke+TIA rate 3%/year; 95% CI 0.4-5.25%/year). There was no case of prosthetic valve dysfunction or PVE. Freedom from reoperation due to procedure-associated complications was 97.6% (one aortic dissection, two major bleeds). Paravalvular leak was detected in 19 cases, and graded trivial or mild in 17 cases (11 grade 0-I, six grade I), and moderate in two cases (grade I-II in one, grade II in one). No patient needed reoperation due to paravalvular leak. Left ventricular (LV) function was normal in 80 cases, but was impaired mildly in 20 cases, moderately in 16, and severely in eight. Bicycle exercise testing in 92 patients (73%) showed median exercise performance (81.4+/-23.9% of normal) after correction for age and weight. Cerebral magnetic resonance imaging was performed in 64 patients (50.8%); median MRI score was 2.0+/-1.8 according to a 12-scaled score system. CONCLUSION: The overall incidence of echocardiographic paravalvular leak graded more than trivial or mild was low (1.6%) in patients followed for a mean of 1.1+/-0.5 years (range: 1-27 months) after valve replacement with Silzone-coated heart valve prostheses. No patient required reoperation due to paravalvular leak; moreover, the stroke rate (1.5%/year) was low in these patients. The present data indicated no significant disadvantages or higher rate of complications related to silver coating compared with other, non-silver-coated prostheses. Future investigation is needed to determine long-term outcome.

Adult↗

Direct confocal microscopy studies of the bacterial colonization in vitro of a silver-coated heart valve sewing cuff.

The antimicrobial coating of prosthetic heart valve sewing cuffs has been considered a potentially effective method for preventing prosthetic valve endocarditis. Although traditional in vitro bacterial adherence studies are often useful as screening tools, they can be inadequate in examining the antiinfective efficacy of antimicrobial-coated devices. We conducted a pilot in vitro study to directly assess the antimicrobial activity of a silver-coated sewing cuff versus uncoated cuff using confocal scanning laser microscopy. Staphylococcus epidermidis adhered more to the surfaces of the silver-coated sewing cuff compared with the uncoated cuff. These pilot in vitro results cast a doubt on the antiinfective efficacy of silver-coated prosthetic heart valve sewing cuffs and suggest further assessment should be carried out using animal studies.

Anti-Bacterial Agents↗

[In vitro investigation of biological and technical prosthetic heart valves using MRI: evaluation of possible deflection and heating of the implants].

PURPOSE: In vitro evaluation of possible deflection and heating of present-day prosthetic heart valves during MR imaging at 1.5 T. METHODS: 17 prosthetic heart valves, 12 technical and 5 biological, were investigated using a 1.5 Tesla Siemens Vision system. Deflection was measured at the edge of a 1.5 Tesla superconducting magnet. Each valve was then submerged in a vial of a 1/1 electrolyte solution and temperature was measured before and after imaging with a turbo-spin-echo sequence (TR 5200 ms, TE 138 ms, Flip angle 180 degrees, acquisition time 10.5 minutes, length of echo train 29). MR imaging was performed with phase encoding parallel and perpendicular to the plane of the valves. RESULTS: None of the investigated prosthetic heart valves were deflected. The maximal observed temperature rise was 0.5 degree C. During MR investigation of the prostheses, artifacts caused by metallic parts were less evident using a spin-echo sequence than a gradient-echo sequence. CONCLUSIONS: Patients with the tested present-day prosthetic heart valves can be safely imaged by MRI.

Bioprosthesis↗

Intracranial hemorrhage due to long-term anticoagulant therapy in patients with prosthetic heart valves--four case reports.

Four patients with prosthetic heart valves suffered intracranial hemorrhage (cerebral hemorrhage in one patient, cerebellar hemorrhage in one, and chronic subdural hematoma in two) during long-term oral anticoagulant drug therapy (warfarin). In all patients, warfarin was discontinued and its effect neutralized by vitamin K, then surgery was performed after the thrombotest value exceeded 50%. No uncontrollable bleeding occurred at surgery. Warfarin was discontinued until 3-7 days postoperatively. Intravenous heparin administration was used to prevent embolic complications and the dose was modified based on the activated clotting time measured at the bedside. One patient, who could not receive heparin administration because of massive bleeding, developed myocardial infarction due to coronary artery thromboembolism 2 days after operation and died 4 days later. The other patients received heparin administration and were alive and well at the most recent follow-up examinations. Heparin administration monitored by activated clotting time is a useful method to prevent embolic and bleeding complications in the surgical treatment of intracranial hemorrhage in patients with prosthetic heart valves receiving long-term anticoagulant therapy.

Cerebral Hemorrhage↗

An overview of artificial heart valve replacement in infants and children.

Prosthetic heart valve replacement in infants and children poses unique problems. This article provides an overview of the factors specific to children with regard to indications and timing of valve replacement, types of artificial valves, constraints, and ramifications of valve choice in children. Anticoagulation, pregnancy, and other issues related to long-term management are reviewed.

Adolescent↗

Platelet interaction with pyrolytic carbon heart-valve leaflets.

Although the newest generation of mechanical heart-valve prosthetics constructed either partially or wholly of lowtemperature isotropic pyrolytic carbon (LTIC) have significantly reduced thromboembolic complications compared with early-generation mechanical valves (e.g., Starr-Edwards), thromboembolism remains an important clinical complication. In the present study, high-resolution, lowvoltage scanning electron microscopy (HR-LV-SEM) was used to examine the structure and platelet interaction properties of LTIC valve leaflets manufactured by both Carbo Medics, Inc. and by St. Jude Medical, Inc. Valve leaflets from both manufacturers, prepared and polished exactly as used in clinical heart valves, had similar surface energetics and elemental composition. Examination with LV-SEM revealed a rough and complex three-dimensional surface structure with nanometer- to micron-size features. In vitro adhesion of human platelets on the LTIC materials and Formvar were evaluated in the presence of 1 mg/mL albumin. Platelet-surface activation, as evaluated by shape change, spread area, and deposition, was extremely extensive on the LTIC materials compared with the Formvar positive control material. LTIC-adherent platelets were extremely thin, and closely followed the rough LTIC contours, greatly limiting their visibility with conventional SEM. These observations demonstrate that LTIC surfaces can extensively activate platelets even in the presence of albumin, thereby suggesting that platelet interactions with pyrolytic carbon may have a significant role in mechanical-valve thromboembolism.

Biocompatible Materials↗

[Study of heart valve function on obese patients treated with sibutramine].

BACKGROUND: Some anorectic drugs have been related with he development of heart valve lesions. Sibutramine is a new anorectic drug used for the treatment of obesity. Although data reported to date suggest that sibutramine does not induce heart valve lesions, there are no published reports performing longitudinal echocardiographic studies before and after treatment with sibutramine. PATIENTS AND METHODS: Consecutive series of 16 obese patients who underwent Doppler-echocardiography before and after treatment with sibutramine. RESULTS: After 6 months of treatment, at 10 mg/day dose, sibutramine does noe appear to induce heart valve lesions. CONCLUSIONS: Sibutramine does not induce heart valve lesions when it is used in short-term treatment courses.

Adult↗

A new diagnostic procedure for assessing intracardiac flow disturbances in patients with heart valve disease.

BACKGROUND: Until now no diagnostic technique was available for the three-dimensional (3D) study of intracardiac blood flow abnormalities in patients with heart valve disease. 3D color Doppler is a new diagnostic technique first developed at our institution. METHODS: The 3D reconstructions of the blood flow velocity data have been obtained from conventional multiplanar transesophageal or transthoracic Doppler echocardiographic examinations. We analyzed 111 reconstructions of color Doppler data obtained from 85 patients with different heart valve diseases who underwent intraoperative transesophageal echocardiography. Sixty-nine patients had a significant mitral regurgitation, 7 mitral stenosis, 9 aortic regurgitation, 12 aortic stenosis, 14 tricuspid regurgitation. Three patients had pulmonary regurgitation associated with mitral valve disease. RESULTS: 3D color Doppler disclosed the complex spatial spreading of the blood flow abnormalities caused by heart valve disease. New patterns of intracardiac blood flow disturbances could be observed and classified. CONCLUSIONS: This paper shows the first clinical applications of 3D color Doppler in patients with heart valve disease. The new insights derived from the 3D study of intracardiac blood flow dynamics revealed a great impact of this technique on the clinical management of patients with heart valve disease.

Coronary Circulation↗

Oral disease burden in patients undergoing prosthetic heart valve implantation.

BACKGROUND: Valvular heart disease predisposing to endocarditis and requiring prosthetic valve implantation is common among the elderly. Spontaneous bacteremias associated with acute or chronic oral/odontogenic infections may represent a far greater cumulative risk for the development of endocarditis than do occasional health care procedures administered in a professional setting. METHODS: To determine the oral disease burden in patients undergoing mechanical or bioprosthetic heart valve implantation, we performed a comprehensive clinical and radiographic regional examination on 156 consecutive patients, with emphasis on identifying acute and chronic oral/odontogenic infections and conditions. RESULTS: The mean number of remaining teeth in the cohort was 19.32; of these, 1.07 were carious, involving a mean number of 2.51 tooth surfaces. In addition, 15.38% of the patients had evidence of acute or chronic periapical abscesses, and 43.6% of the patients had moderate to advanced periodontitis. CONCLUSIONS: In view of the substantial morbidity and mortality associated with prosthetic valve endocarditis and based upon the high incidence of dental disease identified in patients undergoing valvular operations, routine preoperative dental assessment should be deemed a "medical necessity" by third-party payors. Appropriate therapeutic intervention should be initiated whenever possible before valve implantation.

Adult↗

Comparison of a daily fixed 2.5-mg warfarin dose with a 5-mg, international normalized ratio adjusted, warfarin dose initially following heart valve replacement.

Patients starting oral anticoagulant therapy after heart valve replacement initially require a lower target international normalized ratio (INR) (2.0, range 1.5 to 2.6) because of a higher risk of bleeding until pericardial wires are removed. In a previous retrospective analysis, we observed a higher sensitivity to warfarin in these patients compared with nonsurgical patients. In a randomized clinical trial, we compared a fixed, lower dose of warfarin (2.5 mg) with the standard treatment consisting of a 5-mg loading dose, then adjusted to the target INR during the first 5 days of anticoagulation. INRs were measured daily, but the fixed dose was only modified on day 3 if the INR was <1.5 or >3.0. One hundred ninety-seven patients were considered eligible for the study. The 2 groups were well matched according to age, gender, body mass index, concomitant treatments, and type of valves implanted. The proportion of INRs >2.6 during the study period was 42.5% in the 5-mg group and 26.2% in the 2.5-mg group (p <0.05), and the proportion of INRs >3.0 on day 3 was 23.9% and 9.5% (p <0.05), respectively. In the 2.5-mg group, 35.7% of patients had an INR <1.5 on day 3 and had the dose increased (vs 3.5%, p <0.001); however, in the 5-mg group, 95.6% had the initial dose reduced, 49.6% had the dose withheld for at least 1 day, and the mean dose during the 5 days of study was 3.08 mg. Average time to achieve therapeutic range was higher in the 2.5-mg group (2.72 vs 1.98 days, p <0.0001), but the approach to the targeted INR was more regular, and the gap between target and mean INR on day 5 was smaller. There were no bleeding or thromboembolic complications in either group. Thus, a lower loading dose of warfarin in patients after heart valve replacement reduces excessive anticoagulation and offers a more regular achievement of the therapeutic target by reducing the number of dose adjustments. Daily monitoring of the INR is still recommended.

Aged↗

In vitro re-endothelialization of detergent decellularized heart valves under simulated physiological dynamic conditions.

The production of viable biological heart valves is of central interest in tissue engineering (TE). The aim of this study was to generate decellularized heart valves with an intact ultra-structure and to repopulate these with endothelial cells (EC) under simulated physiological conditions. Decellularization of ovine pulmonary valve conduits was performed under agitation in detergents followed by six wash cycles. Viability of EC cultures exposed to washing solution served to prove efficiency of washing. Resulting scaffolds were free of cells with preserved extracellular matrix. Biomechanical standard tension tests demonstrated comparable parameters to native tissue. Luminal surfaces of decellularized valvular grafts were seeded with ovine jugular vein EC in dynamic bioreactors. After rolling culture for 48 h, pulsatile medium circulation with a flow of 0.1 L/min was started. The flow was incremented 0.3 L/min/day up to 2.0 L/min (cycle rate: 60 beats/min), while pH, pO2, pCO2, lactate and glucose were maintained at constant physiological levels. After 7 days, a monolayer of cells covered the inner valve surface, which expressed vWF, indicating an endothelial origin. A complete endothelialization of detergent decellularized scaffold can be achieved under simulated physiological circulation conditions using a dynamic bioreactor system, which allows continuous control of the culture environment.

Animals↗

Introduction of a flexible polymeric heart valve prosthesis with special design for aortic position.

OBJECTIVE: Current prosthetic heart valves necessitate permanent anticoagulation or have limited durability and impaired hemodynamic performance compared to natural valves. Recently a polymeric valve prostheses with special design for mitral position demonstrated excellent in vitro and in vivo results with improved durability and no need for permanent anticoagulation. In this study, a respective flexible polymeric aortic valve is presented and in vitro and in vivo results are reported. METHODS: The aortic prosthesis (ADIAM lifescience AG, Erkelenz, Germany) is entirely made of polycarbonaturethane. The tri-leaflet flexible prosthesis mimicks the natural aortic valve and has a diminished pressure loss and reduced stress and strain peaks at the commissures. The valve underwent long-term in vitro testing and in vivo-testing in a growing calve animal model (20 weeks, 7 aortic valves) and was compared to two different commercial bioprostheses. RESULTS: The polymeric aortic heart valve substitute demonstrated excellent in vitro and in vivo hemodynamics. Five/seven animals with aortic PCU-prostheses had an excellent clinical long-term course. The explanted valves showed a variable degree of calcification. Two of the seven animals died at 27 and 77 days due to pannus overgrowth causing severe LVOTO without degeneration of the valve itself. Both animals with commercial bioprostheses had to be sacrificed because of congestive heart failure related to structural degeneration of the bioprosthesis after 10 and 30 days of implantation. There was no increased thrombogenity of the PCU valves compared to bioprostheses. CONCLUSION: The new flexible polymeric aortic valve prosthesis is superior to current bioprostheses in animal testing.

Animals↗