Heart failure in children -- mechanical assistance.

The use of mechanical circulatory support for the treatment of heart failure in the pediatric population has become increasingly important in pediatric heart surgery units; however, the treatment options for the pediatric population have not attained the same level of technological development as we have seen for the adult population. The use of mechanical assistance as a bridge to transplantation or a bridge to recovery are the main indications for mechanical circulatory support in infants and children. The problem of organ donor shortage is even worse compared to the situation in the field of adult heart transplantations. Especially in Europe however, newly developed pulsatile, paracorporeal ventricular assist devices designed for long-term assist in children have demonstrated their ability to provide excellent results beyond the abilities of extracorporeal membrane oxygenation and centrifugal pumps, which are still the mainstay of mechanical support in children worldwide. Especially in the group of the smallest patients, the use of the most appropriate form of circulatory assistance has to be carefully considered as the co-incidence of respiratory failure as well as other complex physiological situations will severely influence the outcome.

In vitro modelling of tissue using isolated vascular cells on a synthetic collagen matrix as a substitute for heart valves.

BACKGROUND: Tissue engineering is a promising approach for obtaining lifetime durability in biological heart valves. Basic questions with respect to the selection of suitable cell populations as well as scaffolds remain unsolved. The purpose of this study was to develop a tissue-like substitute in vitro for replacement of diseased valves in vivo. METHODS: Smooth-muscle cells (SMCs) were isolated from human and porcine aortic tissue using the 'explant technique' and endothelial cells from collagenase digestion. Seeding and cultivation of isolated cells was performed on a type-I collagen matrix. The scaffold-cell specimen was investigated using light and electron microscopy. Cupromeronic blue and immunoprecipitation were used for ultracytochemical staining. RESULTS: SMCs were allowed to grow to multilayers and migrate into the collagen network. We found a tissue-like morphology in these samples characterised by several layers of cells, spaces between the cell layers filled with newly formed extracellular matrix components, compartmentalisation of proteoglycans and their association with fibrilar matrix and the cell surface. Endothelium cells covered the SMCs of the scaffold with a histological topography similar to heart valves. CONCLUSIONS: This is an approach for in vitro modelling of tissue-like substitutes and preparing plane multicellular tissues as substitutes for heart valves. This model may also be used for cell biological investigations of cell-matrix interactions.

Feasibility and risks of heart surgery in very elderly: analysis of 200 consecutive patients of 80 years and above.

A continuing increase in the number of very elderly patients with symptomatic heart disease referred for cardiac surgery has been observed in the past. Since 1990 all patients of 80 years and above have been included in a prospective study. We report on the results of the first 200 consecutive patients (mean age: 82.2+/-2.1 years). Operative procedures ranged from isolated myocardial revascularization and valve replacement to very complex operations. In a majority of patients, the operations had to be performed as urgent or emergency cases because of advanced heart disease. Overall 30 day mortality was 9.5%. More than two thirds of patients needed treatment of perioperative complications. During long-term follow-up, cardiac surgery in octogenarians has proved to be very effective with excellent functional status and quality of life. Because of favorable results elderly patients should not be denied the benefits of cardiac surgery requiring utilization of significant medical resources.

Primary tissue failure of bioprostheses: new evidence from in vitro tests.

BACKGROUND: Primary tissue failure, which is mainly caused by calcification, is still the limiting factor in the long-term outcome of heart valve bioprostheses. Even though the precise nature of this process is not fully understood, in vitro tests have been developed to reproduce and predict calcification for individual bioprostheses. METHODS: In vitro calcification testing was performed by using an accelerated pulsatile valve tester which was adapted for testing stented as well as stentless bioprostheses with physiological fluid dynamics. A total of 84 bioprostheses (porcine, pericardial and stentless porcine of different manufacturers) were cyclically loaded at a test rate of 300/min at 37 degrees C within a rapid calcification fluid with CaxP = 130(mg/dl)2 at pH 7.4. Calcification was assessed by microradiography after 12 x 10(6) cycles. In a previous step, holographic interferometry was performed to identify irregularities of valve leaflets in order to predict later calcification. Selected specimens of calcified bioprostheses underwent histology, transmission (TEM) and scanning (SEM) electron microscopy. Tissue mineralization was investigated by coupling SEM, electron microprobe analysis (EMPA) and X-ray powder diffraction (XRPD) methods. RESULTS: For all tested bioprostheses, a significant calcification was achieved within 4 to 6 weeks of ongoing testing, and the degree of calcification increased with time. A significant correlation between calcification and leaflet irregularities (detected by holographic interferometry) was found (r = 0.80, p = 0.001). Calcification varied between individual bioprostheses, and significant differences were detected for different groups (calculated as percentage of total leaflet area, mean +/- SD): porcine stented (37.3 +/- 12.0%), bovine stented (23.0 +/- 8.9%), porcine stentless (16.2 +/- 7.6%). Histological and ultrastructural investigation showed intrinsic calcification involving both the spongiosa and fibrosa with collagen fibrils, interfibrillar spaces and cells as early sites of calcification. There was clear evidence of apatite crystallization, and observations made with in vitro calcification were quite similar to those occurring with in vivo implanted bioprostheses. CONCLUSION: In vitro tests can reproduce intrinsic calcification of bioprostheses even in the absence of viable biologic host factors. Moreover, degree and sites of calcification have become predictable. This enables the development and evaluation of bioprostheses with reduction of animal experiments. From our results obtained with a broad range of available bioprostheses, stented bovine and stentless porcine valves seem to be superior to conventional stented porcine bioprostheses with regard to leaflet calcification.

Dynamic in vitro calcification of bioprosthetic porcine valves: evidence of apatite crystallization.

OBJECTIVE: Calcification is the most important cause of structural deterioration of glutaraldehyde-fixed bioprosthetic valves. Devitalization of tissue favors calcium deposits in the shape of apatite crystals. Host factors influence the extent and progression of calcification, but the phenomenon can also occur in vitro in the absence of a viable milieu. Whether calcific deposits obtained in vitro are similar to those found in vivo is unknown. METHODS: Four porcine frame-mounted bioprostheses (St Jude Medical Bioimplant; St Jude Medical, Inc, St Paul, Minn) were tested in vitro by using a pulsatile accelerated calcification testing device at a frequency of 300 cycles per minute at 37 degrees C for 19 x 10(6) cycles with a rapid synthetic calcification solution (final product [calcium x phosphate], 130 mg/dL(2)). Three of the same type of xenografts explanted from human subjects because of calcific failure (time in place, 108 +/- 25.63 mo) served as control grafts. Each sample underwent gross and x-ray examination, histology, transmission and scanning electron microscopy, atomic absorption spectroscopy, electron microprobe analysis, and x-ray powder diffraction methods. RESULTS: All in vitro bioprostheses were heavily calcific, with intrinsic Von Kossa stain-positive deposits and a mean calcium content of 205.285 +/- 64.87 mg/g dry weight. At transmission electron microscopy, nuclei of calcification involved mostly collagen fibers and interfibrillar spaces and, more rarely, cell debris and nuclei. Electron microprobe analysis showed a Ca/P atoms ratio of 4.5:3, a value intermediate between hydroxyapatite and its precursor, octacalciumphosphate. X-ray powder diffraction showed a well-separated and sharp peak, which is typical of hydroxyapatite. Aggregates of plate-like crystals up to 8 microm in size were observed at scanning electron microscopy, with a typical tabular hexagonal shape consistent with apatite. The morphologic and chemical findings in human explants were similar. CONCLUSIONS: Intrinsic calcification of glutaraldehyde-fixed porcine valves was induced in vitro. Electron microprobe analysis and x-ray powder diffraction findings were in keeping with apatite crystallization, such as that occurring in valve xenografts implanted in vivo. The model may be of value to accelerate the screening of anticalcific agents and may reduce the need for animal experiments.

Use of an intraaortic balloon pump in patients with impaired left ventricular function.

Prophylactic use of an intraaortic balloon pump (IABP) prior to open-heart surgery in patients with impaired left ventricular function is still under debate. Patients with left ventricular ejection fraction (LVEF) < 40% were therefore compared according to time of IABP placement, viz. preoperative (n = 56), intraoperative (n = 40) or postoperative (n = 17), and also with patients who did not receive mechanical support despite LVEF < 40% (n = 78). The main indication for preoperative IABP insertion was severely impaired left ventricular function (80%), while patients with intraoperative or postoperative IABP placement mainly presented with low cardiac-output syndrome (70%/53%). Preoperative IABP was associated with a low mortality rate (8.9%), whereas patients with intraoperative or postoperative IABP placement had a high mortality risk and an increased catecholamine requirement. Of the patients scheduled for surgery without prophylactic IABP, 19% required intra- or postoperative insertion. Prophylactic placement of IABP thus reduced the mortality rate as well as the postoperative need for mechanical and catecholamine support. Need for intraoperative IABP insertion was associated with high mortality, whereas the outcome after postoperative IABP placement depended on the indication for the measure.

Postoperative death should be followed by autopsy - an analysis of the autopsy findings of the years 1990 and 1991 in a heart surgery center.

BACKGROUND: In this retrospective analysis of all autopsies performed in 1990 and 1991 on cardiac surgery patients who died before discharge from our university hospital, we intended to test the use of postmortem examination among cardiac surgery patients. METHODS: Perioperative data of all patients who underwent autopsy because of postoperative death during this time period were collected using a retrospective analysis of hospital and autopsy records. RESULTS: In 1990 and 1991 a total of 2407 patients underwent cardiac surgery with extracorporeal circulation at our institution. The in-hospital mortality was 2.9% (n=36) in 1990 and 3.3% (n=40) in 1991. For most of all patients who died during the postoperative course, we found a highly symptomatic cardiac disease and significant co-morbid conditions. The autopsy rate was 46.1% (35/76 patients). Cardiac failure with shock symptoms was the leading course of death (68.6%). In 22.9% of these patients (n=8) the autopsy provided information which had not been clinically recognized (e.g. myocardial infarction, thrombosis of bypass grafts, pneumonia) but might have altered the postoperative therapy if it had been. CONCLUSIONS: Despite the well-known trend of decreasing autopsy rates in the western world we believe that the postmortem examination is a most valuable diagnostic tool in the setting of a university cardiac surgery unit. Our results confirm the importance of autopsies for all patients who die after the operation, because a significant part of autopsies reveals major discrepancies between clinical and postmortem diagnoses. In an effort to maintain a high quality of treatment and education the autopsy rate of a hospital is of utmost interest.

Holographic interferometry and in vitro calcification: comparing pericardial versus porcine bioprostheses.

BACKGROUND AND AIMS OF THE STUDY: Structural valve deterioration of bioprostheses is mainly caused by progressive calcification. It has not yet been convincingly demonstrated whether pericardial or porcine bioprostheses are more prone to calcification. METHODS: A previously described in vitro test protocol consisting of non-destructive holographic interferometry, which permits quantitative deformation analysis of heart valves and accelerated dynamic calcification in vitro was used to evaluate five stented pericardial bioprostheses of different sizes and design (three or two leaflets) from one manufacturer. The extent of calcification was assessed after up to 20 x 10(6) cycles in the valve tester by microradiography, and areas of calcification were compared by holographic interferometry using computerized image processing. Calcification was confirmed by EDX-analysis and Von Kossa staining. Results were compared with in vitro testing of 25 porcine bioprostheses from different manufacturers. RESULTS: The tested pericardial bioprostheses had an individual distribution of mechanical stresses detectable by holographic interferometry, which resulted in different calcification of valve leaflets. A strong correlation between calcification and stress distribution was found (correspondence of affected areas: 82.3 +/- 10.1%, r = 0.97). Variability in calcification and stress distribution, respectively, of pericardial valves compared well with our findings for porcine prostheses. Overall, the extent of leaflet calcification was not statistically different for pericardial and porcine bioprostheses (p = 0.21). CONCLUSIONS: The biological material of bioprostheses (pericardial versus porcine) does not seem to be the crucial factor in the calcification process. Mechanical stresses detectable by holographic interferometry have a more pronounced impact and predict calcification of individual prostheses, at least in the in vitro setting.

In vitro testing of bioprostheses: influence of mechanical stresses and lipids on calcification.

BACKGROUND: Structural valve deterioration of bioprostheses is mainly caused by the progressive development of calcification. Mechanical stresses or lipid deposits in porcine aortic leaflets have been proposed as major factors contributing to the calcification process. METHODS: A new test protocol consisting of nondestructive holographic interferometry, which allows a quantitative deformation analysis of heart valves, and accelerated dynamic in vitro calcification was used. The rapid calcification fluid contained a final combined calcium and phosphorus concentration of 130 (mg/dL)2 in barbital buffer solution. The calcification of 32 bioprostheses donated by different manufacturers (SJM Bioimplant, Biocor standard, Biocor No-React, Carpentier-Edwards SAV, Bravo, pericardial prototype) was assessed after up to 25 x 10(6) cycles by microradiography and the areas of calcification were compared with the holographic interferograms. The distribution of lipid droplets of four porcine prostheses were visualized by Sudan III stain before the calcification process. RESULTS: Most of the tested bioprostheses had areas presenting with stress concentrations, and the dynamic in vitro testing resulted in leaflet calcification corresponding to the holographic irregularities. A strong correlation between calcification and stress distribution or lipid accumulation was found (r = 0.72; r = 0.81, respectively). After 19 x 10(6) cycles, the Carpentier-Edwards SAV and the pericardial valves had significantly less calcification than other prostheses tested (p = 0.003), but the variation among individual prostheses from the same manufacturer was even more pronounced. CONCLUSIONS: Mechanical stresses or lipid accumulation seems to play an important role in the calcification process of bioprostheses. Quality control of bioprosthetic valves using holographic interferometry has the potential to predict calcification before implantation.

[Effect of pre-existing lipids on calcinosis of swine heart valve bioprostheses. A study of a dynamic in vitro model]. / Einfluss präexistenter Lipide auf die Verkalkung von Schweinebioklappenprothesen. Eine Untersuchung am dynamischen In-vitro-Modell.

Calcification is one of the main causes of failure of porcine bioprosthetic heart valves, a problem which has not been satisfactorily solved to date. Previous studies have shown that calcification is decreased in porcine heart valves that have undergone treatment for lipid extraction. The relation between lipid distribution and calcification of seven new commercially available porcine bioprosthetic heart valves (St. Jude Medical, Bioimplant) is assessed by Sudan red III staining to show preexisting lipids. All porcine bioprosthetic valves contained lipids to different degrees. Five valves were subjected to the pulsatile accelerated calcification process for 4 weeks. Distribution and level of calcification were evaluated by radiography and compared to the Sudan red-stained fatty areas. Comparison of the calcifications detected by radiography and the macroscopically detected lipids showed a coincidence of 57-66%. Two porcine bioprosthetic valves were histologically prepared and stained with Hematoxylin and von Kossa's stain, respectively. By light microscopy, the von Kossa staining revealed microcalcifications and polarizing microscopic investigation showed birefractive substances in areas with lipid deposits. These preexisting substances in porcine valve tissue may play a determinative role in the calcification of the tissue. Substantial studies are necessary to further determine the role of preexisting lipids in calcification.

Heart surgery in patients aged eighty years and above: determinants of morbidity and mortality.

Escalating medical costs, limitation of resources and the necessity to provide cost-effective medical care have created a need for systematic risk stratification and cost-benefit analyses in the background of an ongoing discussion. Results of heart surgery in octogenarians have been evaluated in a prospective single-center, study since 1990. 101 consecutive patients (55/ 101 = 54.5% female) aged 80 years and above (median: 81 years; interquartile range [IQR]: 80.0-82.5, total range [TR]: 80-92 years) undergoing open heart surgery at our institution between January 1990 and March 1996 were included into this prospective study. Prior to surgery, most patients were severely symptomatic being in functional NYHA classes either III (56.4%) or IV (31.7%). 61/101 (60.4%) patients underwent isolated coronary artery bypass grafting (CABG), 23 (22.8%) had aortic valve replacement (AVR), 14 patients (13.9%) had CABG combined with AVR or double valve replacement and 3 (3.0%) had mitral valve repair. Follow-up (median: 23.0 months. IQR: 10.5-39.0, TR: 1-72) was focused on long-term morbidity and quality of life. The impact of preoperative and operative risk factors on morbidity and mortality was determined by uni- and multivariate statistical analysis. The 30-days overall mortality in this study was 7.9%. The postoperative course was uneventful for 27 (26.7%) of our patients. Univariate risk factors of postoperative mortality were: left main stem disease (p < or = 0.044), ejection fraction < 45% (p < or = 0.006), preoperative intensive care unit (ICU) (p < or = 0.002), urgent or emergency operation (p < or = 0.034). The only independent predictor of operative mortality was preoperative ICU-stay (p < or = 0.008). Significant risk factors for the number of postoperative complications in the multivariate analysis were: prior stroke (p < or = 0.04), diabetes mellitus (p < or = 0.02), New York Heart Association (NYHA) class IV symptoms (p < or = 0.002) and prolonged cross-clamping time (p < or = 0.001). Mean postoperative length of stay in the ICU was 3.9 +/- 3.9 days. Late morbidity was not related to postoperative complications. Cumulative survival was 87.9%, 79.5% and 72.9% at one, two or five years, respectively. After hospital discharge, 67/93 patients (82.8%) were in NYHA functional class I or II. Cardiac surgery in very elderly patients can be performed with acceptable operative risk and a favorable long-term outcome. The individual patient risk-profile including significant co-morbid conditions and severity of the heart disease predicts not only survival but the extent of perioperative morbidity.

A new in vitro test method for calcification of bioprosthetic heart valves.

To investigate the calcification behavior of different bioprosthetic heart valves and verify possible hypotheses of the etiology of valve calcification, an accelerated pulse tester for bioprostheses was developed, whereby up to ten valves can be tested under identical test conditions. Each valve was mounted in a separate compartment on a piston and cyclically moved through a calcifying solution at frequencies of up to 800/min at 37 degrees C: An appropriate calcifying solution was evaluated by incubation tests of bovine and porcine tissue. Calcification was confirmed by measuring Ca and phosphate depletion by atomic absorption spectroscopy, von Kossa staining, EDAX, and microradiography. The first tests were successfully carried out on porcine valves that had been nondestructively assessed for tissue/stress anomalies by holographic interferometry prior to the calcification test. The tests showed that 75% of irregular fringe pattern areas corresponded to the calcification areas.

Quality control of bioprosthetic heart valves by means of holographic interferometry.

BACKGROUND AND AIMS OF THE STUDY: Limited durability of porcine bioprostheses is mainly caused by the progressive development of calcification. We tested the hypothesis that hidden tissue anomalies or unfavorable stress concentrations of commercially available bioprostheses may lead to later calcification and dysfunction. Application of holographic interferometry for non-destructive testing of biological heart valves enables a full-field analysis of heart valves and reveals deformation irregularities of valve tissue. MATERIAL AND METHODS: We developed an accelerated calcification protocol for bioprosthetic heart valves including an accelerated pulsatile valve tester for simultaneous testing of 10 heart valves under identical conditions and a rapid synthetic calcification fluid containing a final Ca x P of 130 (mg/dl)2 in barbital buffer solution. Ten porcine bioprostheses (St. Jude Medical, Bioimplant) were assessed by holographic interferometry and subjected to the pulsatile accelerated calcification process. Distribution and amount of calcification was evaluated by microradiography after 12 x 10(6) and 19 x 10(6) cycles, respectively. Areas of irregular fringe patterns detected by holography as well as areas of calcification were calculated and compared using a personal computer. RESULTS: All tested bioprostheses had localized or extended areas with holographic irregularities and the accelerated valve testing protocol resulted in even macroscopically visible calcifications at various sites. Comparative analysis of the obtained microradiographs revealed that 74.2% +/- 6.0% of calcified leaflet areas lay within the previously detected holographic anomalies. CONCLUSIONS: Our first results show a strong correlation between holographic anomalies and calcification of porcine bioprostheses. We conclude that suitable methods for evaluation and quality control of bioprosthetic heart valves are available and seem to be predictive with regard to valve calcification.

[Operations in limited left ventricular pump function]. / Operationen bei eingeschränkter linksventrikulärer Pumpfunktion.

The proportion of patients with left ventricular dysfunction (LVD) undergoing open heart surgery is increasing. In this patient group, the perioperative risk is elevated because of the preexisting pathophysiology. Detailed evaluation, interdisciplinary differential therapeutic considerations on the basis of the comparative benefit rationale as well as hemodynamic, antiischemic and antiarrhythmic optimization is mandatory. To plan the operation in patients with coronary artery disease, the issue of reversibility of LVD has to be resolved by sophisticated viability testing. The ultimate decision on revascularization versus aneurysmectomy and scar excision has to be met by the operating surgeon. If the patient's hemodynamics is severely compromised, the perioperative risk may be too high and cardiac transplantation, possibly with mechanical bridging, should be considered. If, in addition, intractable malignant tachyarrhythmias are encountered, antitachycardia operation and defibrillator implantation may be performed. During extracorporeal circulation which is associated with a systemic inflammatory response syndrome the compensatory potential is reduced in patients with LVD, and therefore, the risk of complications such as low-output syndrome, respiratory and renal failure is elevated. Advances in the understanding of pathophysiological mechanisms, an individualized preoperative tailored medical and mechanical therapy for preparation of the operation, anesthesiologic management, cardioprotection and postoperative intensive care have contributed to improvement of outcome in this patient group. Specifically patients with documented evidence of myocardial viability such as angina have profited from surgical revascularization as compared to medical therapy in large scale prospective trials. Perioperative mortality has been lowered to 2-20%. In the absence of angina and presence of overt heart failure and arrhythmias, however, the postoperative 3- and 5-year prognosis of 60% and 35%, respectively, continues to be reduced. Improvement of ejection fraction, angina class, functional capacity and quality of life has been documented in all studies. In conclusion, cardiac operations in patients with left ventricular dysfunction can nowadays be performed with a reasonable risk-benefit ratio, if a careful individualized preoperative evaluation and optimal pre-, intra-and postoperative management is performed.

Comparative analysis of glutaraldehyde-preserved porcine xenografts and fresh or glutaraldehyde-treated human aortic valves by holographic interferometry.

Although calcification and degeneration are recognized as the main causes of bioprosthetic heart valve failure, the reasons for such failure are not well understood. Hidden tissue anomalies in the valves may be the origin of later calcification. Application of hologram interferometry for non-destructive testing enables the detection of such tissue anomalies. A comparative study by holographic interferometry of ten porcine bioprosthetic valves (seven Carpentier-Edwards SAV, two BioImplant and one Valcor) with five human aortic valves before and after glutaraldehyde treatment is presented. Whereas irregularities were detected in the interferograms of eight out of ten bioprostheses, no similar distorted fringe pattern was found in the holographic interferograms of human specimens. The present results suggest that tissue abnormalities exist in standard bioprosthetic valves which are absent in human ones. These irregularities may be the origin of later calcification and valvular dysfunction.