H. A. Huysmans

Stentless Aortic Bioprostheses: Compelling Data From the Second International Symposium

BACKGROUNDnStentless aortic xenografts are an important addition to the range of prosthetic valves. So far their use has been restricted to a limited number of study centers. This report summarizes the principal findings from the Second International Symposium on Stentless Bioprostheses. Attention is focused on the Toronto SPV and Freestyle valves recently approved by the United States Food and Drug Administration.nnnMETHODSnStentless xenografts are used predominantly in elderly patients with aortic stenosis. Implant techniques are more complex than for stented valves, as reflected by longer ischemic and cardiopulmonary bypass times. The valves have been subjected to detailed serial echocardiographic assessment and clinical follow-up.nnnRESULTSnThe hemodynamic characteristics resemble those of the aortic homograft. There is a progressive increase in effective orifice area and decrease in transvalvular pressure gradients with time. Left ventricular mass index and wall thickness normalize between 6 and 12 months postoperatively. Left ventricular remodeling is accompanied by improved symptomatic status and a low incidence of valve-related complications. Limited comparative studies suggest important benefits over stented xenografts. Improved hemodynamics may translate into better bioprosthetic durability.nnnCONCLUSIONSnReproducible and reliable implant methods should be taught carefully, but the hemodynamic advantages are substantial. Stentless xenografts are ideal for the elderly patient with aortic stenosis.

The value of the stentless biovalve prosthesis. An experimental study

Clinical use of the stentless bioprosthesis has not yet been accepted world-wide. Experimental studies are scarce. In a study in growing pigs, 23 aortic valve replacements were performed (7 stented bioprostheses (STB), 10 stentless bioprostheses (SLB) and 6 cryopreserved homografts (CAH)). Valves were studied macroscopically and microscopically after explantation. Five animals died between 1.5 and 4 months after implantation. Two STBs showed extreme calcific degeneration. A third STB animal died suddenly: this STB showed only minimal leaflet calcification. One SLB was stenosed with a large fibrin deposit in one cusp, a second SLB showed slight cusp calcification and three were paracommissural tears in one cusp. In all other animals the valves were explanted after 5 to 6.5 months. All STBs showed severe calcific degeneration. Five SLBs showed mild calcific degeneration, while three others were unaltered after 6 months. All CAHs were free of calcific degeneration, three were perfect, two had a tear in a commisure and another was prolapsed with a fibrin degeneration. The speed and extent of valve degeneration were less than in the STB group. The stentless design is an important contribution which may result in a higher durability of bioprosthetic valves.

Medtronic Freestyle aortic root bioprosthesis: Implant techniques.

Abstract Background: The Medtronic Freestyle aortic root bioprosthesis is a complete porcine aortic root to allow implantation (1) as a subcoronary valve replacement by removing graft sinus aorta, (2) as a cylinder with the sinotubular junction intact within the aorta (root inclusion), or (3) as a complete aortic root replacement. The choice among the three implant techniques depends on surgeon preference or upon the pathology encountered. The advantages and differences among the three implant techniques are examined. Methods: The Medtronic Freestyle bioprosthesis was implanted in 1163 patients in a Food and Drug administration (FDA) clinical trial between August 1992 and October 1997. There were 21 centers in the international trial using a single data repository. Clinical data was collected prior to and at operation, at 3 to 6 months and annually. The data were compiled and statistical analysis performed at the data center. Results: Patients having subcoronary valve implants were older (80% > 65 years) and aortic occlusion time was about 20 minutes less than the other methods. Patients having aortic root replacement presented with more aortic valve insufficiency (20%). Pathology of the aortic root and ascending aorta requiring repair was 26%, and larger (27 mm) valves were used in 40% of patients. Risk of operation was lowest (5.0%) with subcoronary valve implants and highest (11.7%) with root replacement technique. Thromboembolism was higher, early and late, with root inclusion (3.0,3.9%/patient per year) and root replacement (3.2, 3.0%/patient per year) than for subcoronary implants (1.8, 1.6%/patient per year). There were more patients taking warfarin at the 4‐year point with root inclusion (20%) or root replacement techniques (24%) than among patients having subcoronary implants (14%). Explants of the valve occurred in 2% of patients, none of whom had aortic root replacement. Conclusions: The Medtronic Freestyle bioprosthesis is an effective and versatile device for replacement of the aortic valve. It offers implant techniques that can treat the aortic root pathology encountered at surgery and allows the operation to proceed according to surgeon preference.

Altered calcium handling at normal contractility in hypertrophied rat heart

Left or right ventricular hypertrophy was induced by banding of the aorta or pulmonary artery in different groups of rats. After 5 to 10 weeks the degree of hypertrophy was about 15% in left and 80-160% in right ventricles, as determined by weight of the ventricle or by myocyte size. Action potentials and force-interval relationships were measured in papillary muscles isolated from either ventricle. As compared to muscles from control and SHAM-operated rats, hypertrophied papillary muscles showed: (1) Marked prolongation of the action potential and greater degree of post-extrasystolic potentiation. This indicates enhanced influx of Ca2+ probably via Ica; (2) Delayed relaxation of isometric force and faster decay of potentiation, which indicates reduced sequestration of Ca2+ by the sarcoplasmic reticulum; (3) Minor changes in steady-state peak force under standard conditions, which is explained from the opposite inotropic effects of enhanced Ca2+ influx and impaired function of the reticulum. Myocyte volume in the normal left ventricle was almost two times larger than in the normal right ventricle, and this was associated with a longer action potential and greater degree of post-extrasystolic potentiation in left as compared with right ventricular muscles. The rate of decay of potentiation, however, was not different. This might indicate that depressed function of the sarcoplasmic reticulum occurs with pressure-overload hypertrophy and not with normal age-dependent growth.

Enzymatic assessment of myocardial necrosis after cardiac surgery: differentiation from skeletal muscle damage, hemolysis, and liver injury

Plasma activities of various (iso)enzymes were measured in patients after cardiac surgery (n = 114) and after acute myocardial infarction (n = 40). From these activities, the cumulative release of enzymes in plasma was calculated with a two-compartment circulatory model. This model was adapted to transient postoperative changes in plasma volume and similar changes in the transcapillary escape rate of proteins, observed after cardiac surgery and verified in dogs after cardiopulmonary bypass (CPB). Comparison of cumulative release of enzymes with the enzyme content of myocardium, skeletal muscle, and blood cells allows identification of the various sources of enzyme release. Cardiac injury after uncomplicated bypass surgery is only 1.5 +/- 1.5 (mean +/- SD) gram equivalents (gmEq) of myocardium, compared to a loss of 31 +/- 13 gmEq of myocardium after AMI. Peroperative hemolysis is estimated at 68 +/- 15 ml of blood. Total loss of skeletal muscle amounts to 13 +/- 10 gmEq. Some hepatic enzyme release is observed after AMI but not after surgery. Large differences in time course exist between the release of enzymes from myocardium and skeletal muscle and also between myocardial release in the surgery group and in the AMI group. The accuracy of estimations is discussed and indicated as a function of the extent of cardiac injury.

Pulmonary metastasectomy in patients with osteosarcoma.

Between 1980 and 1990, 70 patients with high malignant osteosarcoma of the extremities were treated according to the European Osteosarcoma Intergroup trials. Of the 31 patients with metachronous metastases (group I), 17 underwent pulmonary metastasectomy. Six of the 17 survived 8 months to 4 years after metastasectomy without evidence of recurrent metastatic disease. The type of orthopedic surgical treatment had no influence on the disease free interval (DFI), nor on the overall survival. The DFI was significantly longer (P less than 0.003) in patients with resectable pulmonary metastases. Overall survival was not influenced by the length of the DFI. Six of 11 patients with synchronous metastases (group II) underwent pulmonary metastasectomy, 1 survived longer than 7 months. Nevertheless, overall survival is not significantly different between group I and group II (P = 0.2): 28 patients without pulmonary metastases (group III) had a 95% survival at 5 years. In patients with metachronous metastases, metastasectomy independently had a positive effect on survival (P less than 0.001), but did not cure the patients. Strict patient selection and additional therapy to prevent micrometastases is needed to improve survival.

Extent of myocardial damage after open-heart surgery assessed from serial plasma enzyme levels in either of two periods (1975 and 1980).

Perioperative myocardial damage caused by cardiac surgery in 32 patients operated upon in 1980 is quantified in terms of total quantity of alpha-hydroxybutyrate dehydrogenase released from the heart into the circulation, and compared with perioperative myocardial damage in 32 patients operated upon in 1975. In the five year period between 1975 and 1980, various aspects concerning anaesthesia, pharmacological treatment, and myocardial preservation techniques have been subjected to considerable changes. Comparison of calculated myocardial damage in 1980 with that in 1975 shows a general reduction of about 40% in patients having coronary artery bypass grafting, 75% in patients with aortic valve replacement, and 10% in patients with mitral valve replacement.

Echocardiographic Parameters of the Freestyle Stentless Bioprosthesis in Aortic Position: The European Experience

The objective of this study was to determine normal Doppler and 2-dimensional characteristics of the Freestyle stentless aortic bioprosthesis. The Freestyle aortic bioprosthesis is a new type of aortic xenograft, and experience is limited. We therefore determined the normal range of echocardiographic and Doppler examinations of this valve. Three hundred thirty-nine consecutive patients with a Freestyle aortic bioprosthesis underwent an echocardiographic and Doppler examination according to a common protocol. Investigations were done within 4 weeks after operation, after 3 to 6 months, and after 1, 2, and 3 years. With a valve size from 19 to 27 mm, mean gradients decreased from 7.9 +/- 5.1 mm Hg at discharge to 5.5 +/- 3. 8 mm Hg after 3 to 6 months (P <.001). Thereafter, gradients remained stable. Effective orifice area 1 year after implantation was 1.59 +/- 0.58 cm(2) for the 21-mm valves, 1.92 +/- 0.74 cm(2) for the 23-mm valves, 2.03 +/- 0.64 cm(2) for the 25-mm valves, and 2.52 +/- 0.72 cm(2) for the 27-mm valves (P <.001). The performance index, the ratio of the measured effective orifice area in the patient divided by the effective orifice area measured in vitro, increased from 67% +/- 20% at discharge to 82% +/- 29% after 1, 2, and 3 years. Performance index was especially very high in the smaller-sized valves. After implantation with the subcoronary technique or root-inclusion technique, small cavities could be seen between the native aortic root and the Freestyle valve. Doppler values were evaluated for the Freestyle stentless porcine bioprostheses in the aortic root. Gradients appear to be close to those measured in native valves over a time period of 3 years.

Assessment of hemodynamic function and tolerance to ischemia in the absence or presence of calcium antagonists in hearts of Isoproterenol-treated, exercise-trained, and sedentary rats

The effects of cardiac hypertrophy on the structure, function and tolerance to ischemia of rat hearts have been investigated. Multiple injections of low doses of isoproterenol (ISO) resulted in an increase of heart weight/body weight ratio by 60%, and a decrease of myocardial creatine kinase activity by 25%, as compared to normal rats. Compared to age-matched control rats, rats submitted to a swimming program had a higher heart weight by 20%, but similar values of heart weight to body weight ratio. In isolated perfusion, the functional capacities of hearts from ISO-treated rats were severely depressed compared to normal rat hearts whereas exercise-trained rat hearts performed as well or even better than control hearts. The functional recovery of ISO-treated hearts following cardioplegia-induced arrest for 20 min at 37 degrees C was significantly worse than the recovery of normal hearts, but hearts of exercise-trained rats showed a significantly better recovery than control hearts. Exercise training results in improvement of myocardial blood supply resulting in better preservation of the heart during ischemia, compared to normal hearts. Addition of a combination of verapamil and diltiazem to the cardioplegic solution followed by ischemic arrest for 20 min at 37 degrees C resulted for ISO-treated rat hearts in an improved recovery of cardiac output (99%) compared to cardioplegia in the absence of these drugs (72%). In exercise-trained and control rat hearts, calcium antagonists improved the recovery from cardioplegic arrest of cardiac output from 90% to 92% and from 71% to 87%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Identification of host and donor cells in porcine homograft heart valve explants by fluorescence in situ hybridization

The pathogenesis of the primary tissue degeneration that limits the life‐span of aortic and pulmonary homografts has still not been revealed. Histopathological studies on homograft explants have not given definitive insight into the eventual fate of donor cells, nor have they demonstrated the assumed importance of host cell ingrowth into the graft tissue. In this experimental study, fluorescence in situ hybridization (FISH) is introduced as a new approach to examine the distribution of host and donor cells in homograft explants. Aortic valve replacement was performed with a cryopreserved porcine aortic homograft in three pigs; donor and recipient were of opposite sex. After 4 months, the grafts were explanted and examined by FISH using a biotinylated porcine Y‐chromosome‐specific library probe. Following probe detection with FITC‐conjugated avidin, a clear distinction could be made between cells of host and donor origin without distorting the histological integrity of the explants. There was ingrowth of donor cells into the graft aortic wall and into the valve leaflet, to some extent. In all explants, remaining donor cells were present, though decreased in number. The introduction of FISH in homograft heart valve research provides a powerful tool to study the fate of recipient and donor cellular elements in situ, and may therefore contribute to a better understanding of the histopathological processes that take place in transplanted homograft valves.