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Pattern of anticoagulation control after heart valve surgery at the Kenyatta National Hospital, Nairobi.

OBJECTIVE: To determine the pattern of anticoagulation control for post heart-valve surgery for patients on follow up at Kenyatta National Hospital (KNH). DESIGN: A combined prospective and restrospective hospital-based study. Retrospective period from January 1991 to 31st August 1997, while the prospective period was from 1st September 1997 to 31st November 1999. SETTING: Cardiothoracic surgery clinic, Kenyatta National Hospital, Nairobi. PATIENTS: Post heart valve surgery patients on warfarin and attending the cardiothoracic surgery clinic at Kenyatta National Hospital. MAIN OUTCOME MEASURES: Clinic attendance intervals, average warfarin dosages, interval of dosage change, INR values and variations from accepted normal. RESULTS: A total of 103 patients fulfilled the criteria for inclusion into the study consisting of 77 mitral valve replacements, 18 aortic valve replacements, seven double valve replacements and one mitral valve repair. The total follow up time for the study period is 316.9 patients years. On average, patients attended their anticoagulation clinic once every 59 days. The average dose of warfarin prescribed was 6.81 mg daily (+/-2.67 mg), with double valve replacement patients receiving a statistically significant lower dosage of 6.04 mg (+/-1.36 mg), (95% confidence limits). On average, a warfarin dose change was made 1.48 times a year per patient. For all the patients, the mean INR was 2.50 (+/-1.18). The respective values for mitral, aortic, double valve replacement and the mitral repairs were 2.53 (+/-1.21), 2.32 (+/-1.04), 2.5 (+/-1.05) and 2.02 (+/-0.53), respectively. Mitral valve repair patients maintained a significantly lower level of INR (95% confidence limits). Only during 18% of the follow up time was adequate anticoagulation maintained. During the study period only 6.9% of patients were able to maintain adequate anticoagulation for 50% or more of their follow up time. CONCLUSION: Anticoagulation control at the KNH still needs some improvements in clinic attendance and better dosage adjustments to achieve more appropriate INR values.

Anticoagulants↗

[Perioperative complications after heart valve replacement].

These days, the majority of perioperative complications resulting from operations on heart valves are more a consequence of the increasing age and morbidity of the patients and, despite all cardiac surgical and intensive care innovations, are still more the effect of the procedure on the other organ systems of the patient than being purely of a surgical nature. The surgical short- and long-term results after heart valve operations are significantly influenced by the early detection and adequate management of these manifold complications.

Adult↗

[Echocardiographic evaluation of hemodynamic function of CarboMedics heart valve in the aortic position in patients with small aortic annuli].

Hemodynamic parameter of CarboMedics heart valve in the aortic position was evaluated using Doppler echocardiography in 46 patients with small aortic annuli. The size of prosthetic valve were 19 mm in 6 cases, 21 mm in 15 and 23 mm in 25. In patients with 19 mm valve, trans-valvular peak pressure gradient was 42.2 +/- 11.8 mmHg, mean pressure gradient was 17.3 +/- 9.3 mmHg, and left ventricular systolic pressure was 174 +/- 12 mmHg. These values were significantly larger than those of the other two groups. Effective orifice area index, discharge coefficient, doppler velocity index and stroke volume showed no significant difference among each group. After aortic valve replacement for aortic stenosis, left ventricular mass decreased to around 70% of preoperative value in all groups, but significant left ventricular hypertrophy remained at two years postoperatively. We conclude that hemodynamic performance of CarboMedics heart valve in the aortic position was satisfactory, although 19 mm valve seemed to be fairly small for adult patients and deliberate patient selection is necessary.

Adult↗

Evaluation of carotid artery and aortic intima-media thickness measurements for exclusion of significant coronary atherosclerosis in patients scheduled for heart valve surgery.

OBJECTIVES: We assessed the value of carotid intima-media thickness (CIMT) and thoracic aorta intima-media thickness (AoIMT) in ruling out significant coronary artery disease (CAD) in patients scheduled for heart valve surgery. BACKGROUND: Evaluation of CAD is needed in most patients undergoing heart valve surgery because of the high surgical morbidity in patients with significant CAD, raising the need for sensitive tests to exclude CAD. Coronary angiography is the reference standard, but this invasive procedure is not cost-effective, because more than two-thirds of these patients do not have significant CAD. METHODS: In a pilot study, CIMT and AoIMT cutoff values separating low- from high-risk groups were determined in 96 patients by using receiver-operating characteristic curves. Then, a prospective study was conducted in 152 patients to determine the statistical power of these cutoff values used alone or in combination. In both studies, carotid artery ultrasonography and transesophageal echocardiography were performed before coronary angiography and valve surgery. RESULTS: In the pilot study, CIMT < 0.55 mm and AoIMT < 3 mm were excellent predictors of the absence of CAD. In the prospective study, CIMT and AoIMT criteria were independent predictors of significant CAD in these patients, as assessed by logistic regression analysis. Carotid IMT criterion had 100% sensitivity and 100% negative predictive value. For the AoIMT criterion, sensitivity was 98%, and negative predictive value 99%. Combining the two criteria did not change sensitivity and negative predictive value but increased specificity to 78%. CONCLUSIONS: Measurements of CIMT and AoIMT may be useful in selecting patients who do not require coronary angiography before heart valve surgery.

Aged↗

Commissural dehiscence and pannus formation of porcine heart valve bioprostheses.

From May 1976 to June 2001, 95 porcine heart valve bioprostheses (BPs) were explanted. Among them, 85 prostheses were available for an analysis of structural valve deterioration (SVD). There were 32 Hancock (H) BPs and 53 Carpentier-Edwards (CE) BPs, with a mean implantation duration of 12 +/- 3.5 and 11.0 +/- 4 years, respectively. There were two extraordinary complications. One was commissural dehiscence (CD) of the CEBPs in 10/53 cases (18.9%), with a mean duration of 12.7 +/- 2.7 years. This was not observed in the HBPs. The other was pannus formation in both BPs. In the mitral position, it was 25/32 (78.1%) in HBPs and 37/53 (69.8%) in CEBPs. In the aortic position, it was 4/32 (1.3%) in the HBPs and 11/53 (20.8%) in the CEBPs. We conclude that CD could not be diagnosed preoperatively and anticoagulation is therefore indicated to prevent pannus formation of such prostheses, particularly in those located in the mitral position.

Animals↗

The optimal therapeutic range for oral anticoagulant treatment as suggested by fibrinopeptide A (FpA) levels in patients with heart valve prostheses.

Fibrinopeptide A is a good marker of in vivo thrombin formation. The aim of oral anticoagulants (OA) is to lower in vivo thrombin formation. We therefore assessed FpA levels on several occasions in 38 patients receiving OA for artificial heart valve prostheses and in 20 patients receiving OA for biological heart valve prostheses. The mean FpA level, 1.82 ng ml-1 (SEM 0.14, n = 176), in patients with artificial valves was significantly higher than the mean, 1.02 ng ml-1 (SEM 0.4), obtained in 41 healthy subjects (P = 0.01). FpA mean value for biological valves was 1.41 ng ml-1 (SEM 0.14, n = 76), which was not significantly higher than controls (P = 0.08). A decrease in FpA levels, for both artificial and biological heart valve prostheses, was associated with a parallel increase in the intensity of anticoagulation. When considering FpA values obtained in the optimal therapeutic range for oral anticoagulant treatment, (International Normalized Ratio [INR] between 3 and 4.5), the mean level for artificial valves, 1.87 ng ml-1 (SEM 0.18, n = 102), was significantly higher than the mean value, 1.25 ng ml-1 (SEM 0.16, n = 55), obtained for biological valves. From a biological point of view, this indicates that artificial valves should be kept at a higher intensity of anticoagulation.

Administration, Oral↗

[Nutritional and immunologic state of patients undergoing heart valve surgery].

A series of 60 consecutive patients treated by heart valve replacement surgery under extracorporeal circulation were reviewed. Poor nutrition was assessed in 28% of these cases, the cardiac index in these patients being significantly smaller than in operated patients with normal nutritional states (2.07 +/- 0.8 as against 2.46 +/- 0.7, p less than 0.01). Furthermore, 58% of those with poor nutrition presented postoperative complications: mediastinitis, wound infection, ventricular arrhythmias or secondary pulmonary infection. One death occurred in this group. Postoperative complications in patients with normal nutritional states developed in only 6% and there were no deaths. Duration of hospital stay was significantly longer in patients with poor nutrition (p less than 0.05). Apart from immunoglobulin levels, all immunologic parameters underwent postoperative modifications related to nutritional state. Physiopathologic hypotheses are proposed as well as a programme for increasing nutritional intake in patients in a precarious metabolic state which predisposes them to complications.

Adult↗

Warfarin sensitivity after mechanical heart valve replacement.

We performed a retrospective chart review of 60 patients after mechanical heart valve replacement to assess warfarin sensitivity. The overall international normalized ratio (INR) on day 3 of therapy was 4.1+/-3.9 (range 1.1-17.1). In a control group of 100 patients who received anticoagulation for atrial fibrillation, pulmonary embolism, and deep vein thrombosis, the overall mean INR at day 3 was 1.9+/-0.7 (range 1.0-4.9). The difference between groups was statistically significant (p<0.05). We conclude that patients receiving warfarin after mechanical heart valve replacement are more sensitive to the drug than those receiving it for other indications, and reduced dosages may be necessary during the first 3 days after valve replacement.

Adult↗

Endothelial cell lining of bioprosthetic heart valve materials.

To investigate the conditions for endothelial cell lining of glutaraldehyde-treated bioprosthetic heart valves, we examined in vitro the growth properties of endothelial cells on clinically used pericardial valve material and on glutaraldehyde-fixed pericardium treated with L-glutamic acid. To improve endothelial cell attachment to the valvular surface, we precoated both materials either with fibronectin or with fibrillar collagen (95% type I, 5% type III). Toxicity of glutaraldehyde, released from clinically used valve material, caused endothelial cell death, independent of the type of precoating. Treatment of the valve material with L-glutamic acid resulted in regular endothelial cell proliferation. We found that collagenous precoating, compared with fibronectin precoating, markedly enhanced endothelial cell proliferation and attachment (p less than 0.05). Maintenance of antithrombogenic potency of the seeded cells on L-glutamic acid-treated valve material was proved by regular release of prostacyclin. We conclude that bioprosthetic heart valve materials can be lined with endothelial cells if toxic glutaraldehyde released from the bioprostheses is eliminated.

Animals↗

Ex vivo evaluation of ferromagnetism, heating, and artifacts produced by heart valve prostheses exposed to a 1.5-T MR system.

Ex vivo testing techniques were used to determine the ferromagnetic qualities of, presence of heating in, and artifacts produced by 13 different heart valve prostheses exposed to a 1.5-T (64-MHz) magnetic resonance (MR) system. None of the heart valve prostheses showed a measurable deflection in the 1.5-T static magnetic field. Only minimal artifacts were produced during MR imaging with a fast spoiled GRASS (gradient-recalled acquisition in the steady state) pulse sequence. The largest temperature changes measured during a "worst case" MR imaging sequence (estimated average specific absorption rate, 2.5 W/kg; estimated spatial peak specific absorption rate, 7.6 W/kg) were +0.2 degree C with the implant imaged "in air" and +0.3 degrees C with the implant imaged in normal saline. Therefore, MR procedures performed with a 1.5-T (64-MHz) MR system may be performed safely in patients with any of the 13 different heart valve prostheses evaluated in this study.

Absorption↗

Flow and thrombosis at orifices simulating mechanical heart valve leakage regions.

BACKGROUND: While it is established that mechanical heart valves (MHVs) damage blood elements during leakage and forward flow, the role in thrombus formation of platelet activation by high shear flow geometries remains unclear. In this study, continuously recalcified blood was used to measure the effects of blood flow through orifices, which model MHVs, on the generation of procoagulant thrombin and the resulting formation of thrombus. The contribution of platelets to this process was also assessed. METHOD OF APPROACH: 200, 400, 800, and 1200 microm orifices simulated the hinge region of bileaflet MHVs, and 200, 400, and 800 microm wide slits modeled the centerline where the two leaflets meet when the MHV is closed. To assess activation of coagulation during blood recirculation, samples were withdrawn over 0-47 min and the plasmas assayed for thrombin-antithrombin-llI (TAT) levels. Model geometries were also inspected visually. RESULTS: The 200 and 400 microm round orifices induced significant TAT generation and thrombosis over the study interval. In contrast, thrombin generation by the slit orifices, and by the 800 and 1200 microm round orifices, was negligible. In additional experiments with nonrecalcified or platelet-depleted blood, TAT levels were markedly reduced versus the studies with fully anticoagulated whole blood (p < 0.05). CONCLUSIONS: Using the present method, a significant increase in TAT concentration was found for 200 and 400 microm orifices, but not 800 and 1200 microm orifices, indicating that these flow geometries exhibit a critical threshold for activation of coagulation and resulting formation of thrombus. Markedly lower TAT levels were produced in studies with platelet-depleted blood, documenting a key role for platelets in the thrombotic process.

Biomechanical Phenomena↗

Hydrodynamic function of polyurethane prosthetic heart valves: influences of Young's modulus and leaflet thickness.

The development of flexible polyurethane heart valves has been hindered by material degradation in vivo. Low modulus polyurethane leaflets are regarded as desirable to achieve good hydrodynamic function. However, low modulus materials may suffer high strain accumulation, hence poor durability. Higher modulus materials may improve durability, but may have poor hydrodynamic function. This study examines the hydrodynamic behaviour of biostable polyurethane valves, varying Young's modulus from 5 to 63.6 MPa and mean leaflet thickness from 48-238 microm. Parameters studied included mean pressure gradient, energy losses and regurgitation over 5 equivalent cardiac outputs (3.6, 4.9, 6.4, 8.0 and 9.61 min(-1)) At low cardiac output, modulus was not significantly correlated with any parameter of valve opening. At 9.61 min(-1), modulus significantly influenced mean pressure gradient (p = 0.033). Mean leaflet thickness significantly correlated with mean pressure gradient and energy losses during forward flow at all cardiac outputs (p<0.001). This study demonstrates that, over a wide range of moduli, valve hydrodynamic function is not affected significantly by the material modulus. Leaflet thickness is a highly significant factor. Higher modulus elastomers in a range up to 32.5 MPa may be useful in prosthetic heart valve leaflet manufacture, retaining good hydrodynamic function while potentially extending the lifetime of the valve.

Heart Valve Prosthesis↗

Perioperative bleeding and thromboembolic risk during non-cardiac surgery in patients with mechanical prosthetic heart valves: an institutional review.

BACKGROUND AND AIMS OF THE STUDY: The study aim was to determine the risk of thromboembolic and bleeding complications in patients with mechanical heart valve prostheses who underwent non-cardiac surgery under different regimens of perioperative anticoagulation. Data were analyzed on the basis of surgery type and underlying disease. METHODS: A series of 235 patients (mean age 63 +/- 4.5 years) with one or two mechanical heart valves underwent subsequent non-cardiac surgery comprising abdominal, vascular and thoracic, orthopedic, urologic, neurosurgery, ENT, plastic and reconstructive, and gynecologic operations. Mean interval between heart valve replacement and non-cardiac surgery was 3.9 +/- 3.3 years. Perioperative oral anticoagulation was managed by discontinuation of oral anticoagulation and intravenous heparin administration; or by discontinuation and early postoperative re-institution of oral anticoagulation without intravenous heparin; or by no withdrawal of oral anticoagulation. Patients with bioprostheses were excluded. RESULTS: Overall hospital mortality during non-cardiac surgery was 2.9%. Thromboembolic events included cerebral embolism with transient deficit (n = 3), residual defect (n = 1) and irreversible defect (n = 1), as well as peripheral embolism (n = 11). Hemorrhagic complications included wound hematoma (n = 10) and increased postoperative bleeding (n = 8) with re-exploration in five patients. Thromboembolic complications occurred most often in patients with prosthetic mitral valve and atrial fibrillation; the lowest risk was in patients with sinus rhythm after aortic valve replacement. Most complications occurred after discharge and in patients with surgery for malignancy, within 10 days of instituting oral anticoagulation, and despite a therapeutic INR value. CONCLUSIONS: Minor surgical procedures can be performed safely without discontinuing anticoagulation. When major non-cardiac surgery is planned, discontinuing oral anticoagulation and starting perioperative intravenous heparin minimizes bleeding and thromboembolic risks. Thromboembolic complications may occur within one month of surgery, despite adequate oral anticoagulation, though permanent morbidity is low.

Anticoagulants↗

Tissue engineering of a bioprosthetic heart valve: stimulation of extracellular matrix assessed by hydroxyproline assay.

Creation of an autologous heart valve by tissue engineering offers a promising approach to cardiac surgery. Although we have demonstrated successful formation of native valve analogous tissue in vitro, hemodynamic competence remains a serious problem. The aim of this study was to optimize in vitro formation of collagen as a precondition for mechanical stability of new tissue. Human myofibroblasts were seeded on square sheets of biodegradable scaffolds (control). To stimulate collagen production, one series was cultured with L-ascorbic acid 2-phosphate. In a second series, the seeded scaffolds were subjected to tension by mounting them on a frame. After 4 weeks of culture time, the collagen content of the different series was assessed by hydroxyproline assay. Light and scanning electron microscopy were performed. Hydroxyproline content of the framed scaffolds was 10 times higher than that of the control group (p < 0.05) and 6 times higher than in the unframed scaffolds grown with ascorbic acid (p < 0.05), respectively. Scanning electron microscopy proved extensive formation of solid tissue in the framed samples. These results demonstrate that supplementation of myofibroblast cultures with ascorbic acid, especially if grown on strained scaffolds, significantly increases collagen content, which is crucial for mechanical stability. This concept is a further step toward the creation of a hemodynamically competent autologous heart valve.

Ascorbic Acid↗

Viability in human heart valves prepared for grafting.

Viability of antibiotic sterilized and stored human heart valves obtained at routine necropsy was assessed by tissue culture and protein and collagen synthesis. Only three of 23 valves examined showed any evidence of viability, in striking contrast to earlier work on canine valves obtained under optimal conditions. These findings justify doubts regarding pre-implantation viability in human heart valves prepared for grafting.

Adult↗

Time-frequency analysis of the noise produced by the closing of artificial heart valves: an in vitro study.

Clinical investigations showed that patients with an implanted mechanical heart valve are sometimes disturbed by the noise produced by the valve closing. The aim of this study was to investigate the noise generated by mechanical artificial heart valves with reference to the one produced by biological valves. This type of biological valve was used as a standard because it does not disturb the patient. We used an in vitro approach with a cardiovascular simulator. The noise signal was recorded simultaneously using a hydrophone and an accelerometer. During each cardiac cycle, because of the shortness of the signal (15-25 ms) and of the transient state, rapid frequency dynamics limited the usefulness of stationary analysis techniques for the first heart sound. Therefore, a time-frequency technique was much more convenient than a classic Fourier analysis. We used a discrete wavelet transform that pointed out the time fluctuation of each frequency component. Globally, mechanical valves produced a high sound level within the octave bandwidths centered on 64 Hz up to 512 Hz, while the amplitude of these components decreased rapidly for the biological valve.

Acceleration↗

Cultured interstitial cells from human heart valves express both specific skeletal muscle and non-muscle markers.

Cardiac valve interstitial cells are a phenotypically diverse and dynamic population, comprising myofibroblasts, fibroblasts and smooth muscle cells. To understand how these contribute to valve function and to optimize the choice of cells for seeding tissue-engineered valves, we are fingerprinting interstitial cells from all four human heart valves for useful phenotypic markers. We have begun by selecting markers indicated as of interest from previous work on myofibroblast-like cell lines. We show that interstitial cells express a variety of skeletal muscle contractile proteins and the skeletal muscle transcription factor myogenin, but not the related factors MyoD, myf-5 and MRF4, suggesting partial activation of the muscle programme in these cells. Expression of non-muscle isoforms of creatine kinase (CK-B) and AMP deaminase (AMPD2 and AMPD3) was found in contrast to muscle-restricted isoforms. Non-muscle isoforms of alpha- and beta-tropomyosins were detected specifically in contrast to skeletal muscle-specific isoforms. Several members of the Frizzled (FZD) family of Wnt receptors were also detected. In addition, intact cusps of all four valves from pig were capable of contacting to non-receptor and receptor-mediated stimulation in vitro. We conclude that interstitial cells from human heart valves express various sarcomeric proteins, and suggest that these cells have contractile potential due to a unique pattern of expression of both muscle-specific and non-muscle isoforms of metabolic and structural proteins. This may be under the control of myogenin, activated through specific Wnt/FZD signaling. Identifying such molecular markers could prove useful for engineering allogenic non-valve cell sources for seeding the synthetic valve.

Cells, Cultured↗

Prevention of bioprosthetic heart valve calcification by ethanol preincubation. Efficacy and mechanisms.

BACKGROUND: Calcification of the cusps of bioprosthetic heart valves fabricated from either glutaraldehyde cross-linked porcine aortic valves or bovine pericardium frequently causes the clinical failure of these devices. Our investigations studied ethanol pretreatment of glutaraldehyde cross-linked porcine aortic valves as a new approach to prevent cuspal calcification. The hypothesis governing this approach holds that ethanol pretreatment inhibits calcification resulting from protein structural alterations and lipid extraction. METHODS AND RESULTS: Results demonstrated complete inhibition of calcification of glutaraldehyde-pretreated porcine bioprosthetic aortic valve cusps by 80.0% ethanol in rat subdermal implants (60-day ethanol-pretreated calcium level, 1.87 +/- 0.29 micrograms/mg tissue compared with control calcium level, 236.00 +/- 6.10 micrograms/mg tissue) and in sheep mitral valve replacements (ethanol-pretreated calcium level, 5.22 +/- 2.94 micrograms/mg tissue; control calcium level, 32.50 +/- 11.50 micrograms/mg tissue). The mechanism of ethanol inhibition may be explained by several observations: ethanol pretreatment resulted in an irreversible alteration in the amide I band noted in the infrared spectra for both purified type I collagen and glutaraldehyde cross-linked porcine aortic leaflets. Ethanol pretreatment also resulted in nearly complete extraction of leaflet cholesterol and phospholipid. CONCLUSIONS: Ethanol pretreatment of glutaraldehyde cross-linked porcine aortic valve bioprostheses represents a highly efficacious and mechanistically based approach and may prevent calcific bioprosthetic heart valve failure.

Animals↗