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Biomedical subjects

Roland Hetzer

Publications and source records attributed to Roland Hetzer.

At least 19 recordsLinked to original sources

Impact of heparin-induced thrombocytopenia on outcome in patients with ventricular assist device support: single-institution experience in 358 consecutive patients.

BACKGROUND: Cardiac surgical patients are at an approximate 1% to 2% risk of experiencing heparin-induced thrombocytopenia (HIT), a severe immune-mediated disease that is associated with thromboembolic events. We assessed the occurrence of this disease and its influence on clinical outcome in patients after implantation of a ventricular assist device (VAD). METHODS: This retrospective analysis assessed data from our adult patient VAD program between the years 2000 and 2005. Patients were divided into three groups: those without confirmed HIT ((non)HIT), those in whom the diagnosis of HIT was made before VAD implantation (HIT(pre)), and those who experienced HIT after VAD implantation (HIT(post)). End points assessed were procedural success, as defined by discharge from hospital or transplantation or recovery of the failing heart, as opposed to death before procedural success was achieved. RESULTS: The data of 358 consecutive patients were analyzed. There were 330 (non)HIT patients (91.6%), 15 HIT(pre) patients (4.5%), and 13 HIT(post) patients (3.9%). Procedural success was observed in 50% of (non)HIT patients, 67% of HIT(pre) patients, and 31% of HIT(post) patients. CONCLUSIONS: Heparin-induced thrombocytopenia is a frequent complication in VAD patients and is associated with detrimental outcome when occurring after implantation. Preoperative diagnosis of HIT and the implementation of alternative anticoagulation procedures appears to be associated with better results. Early detection of HIT antibodies before or shortly after VAD implantation and immediate implementation of an alternative anticoagulation regimen may be a strategy to improve outcome.

Adult↗

Association of human leukocyte antigen haplotypes with posttransplant lymphoproliferative disease after solid organ transplantation.

BACKGROUND: Posttransplant lymphoproliferative disease (PTLD) after solid organ transplantation (SOT) is commonly characterized by Epstein-Barr virus (EBV)-driven proliferation of recipient B cells due to impaired immune surveillance in the context of immunosuppression. Because EBV-specific T-cell responses are focused on the level of EBV antigen and epitope choice depending on the individual human leukocyte antigen (HLA) alleles, we hypothesized that certain HLA alleles or a distinct HLA haplotype may influence the risk of development of PTLD after SOT. METHODS: A multicenter case-control study was performed comparing a group of 155 recipients after SOT with development of PTLD with a group of 1996 recipients after SOT without development of PTLD. Alleles, genotypes, and three locus haplotypes were compared of SOT recipients with and without PTLD. RESULTS: The bivariate analysis showed that carrying HLA-A03 was negatively associated (odds ratio [OR] 0.61, confidence interval [CI] 0.40-0.92, P < 0.02) whereas carrying of HLA-B18 (OR 1.79, CI 1.18-2.73, P < 0.006) and HLA-B21 (OR 2.08, CI 1.14-3.77, P < 0.02) were positively associated with PTLD after SOT. HLA-DR analysis demonstrated a significant negative association between the expression of HLA-DR7 (OR 0.46, CI 0.28-0.78, P < 0.004) and PTLD. Three locus haplotype analysis underlined the relevance of a dominant protective effect of HLA-DR7 expression concerning the risk of PTLD development. CONCLUSIONS: Our data suggest an influence of HLA variants on the risk of the development of PTLD. We hypothesize that HLA genes or non-HLA genes within the HLA loci confer a risk modification for the individual patient.

Adult↗

Changes in exercise capacity, ventilation, and body weight following heart transplantation.

AIMS: Peak oxygen uptake adjusted to body weight (peak VO(2)) and ventilatory efficiency (VE/VCO(2)-slope) are important prognostic parameters in chronic heart failure. Our study prospectively examined changes in these parameters over 24 months following heart transplantation (HTx) and evaluated the potentially confounding effects of weight gain. METHODS AND RESULTS: One hundred patients with chronic heart failure (16 female, mean age at HTx 53.9+/-9.6 years) underwent cardiopulmonary exercise testing before and 3, 6, 12 and/or 24 months after HTx. Twenty-five healthy individuals served as matched normals. VE/VCO(2)-slope during exercise improved significantly at 6 (-23.7%), 12 (-21.3%), and 24 months (-32.3%; all p<0.002 vs. baseline). At 6 months, VE/VCO(2)-slopes were similar to the matched normals (31.8+/-4.3), 46 of 78 patients achieved values within the 95% confidence interval of normal. Peak VO(2) increased significantly after HTx at 6 (+31.8%), 12 (+36.2%), and 24 months (+42.2%; all p<0.005). None of the patients reached values within the 95% CI of normal. Although VE/VCO(2)-slope and peak VO(2) were correlated inversely at every time point (p<0.03), reduction in VE/VCO(2)-slope did not correlate with increase in peak VO(2). Symptoms that limited exercise changed from dyspnoea before HTx to leg fatigue after HTx. CONCLUSION: Following HTX, VE/VCO(2)-slope returns to normal values in the majority of patients; however, despite improvement, peak VO(2) remains abnormal in all patients. Symptoms causing patients to stop exercising change from dyspnoea to leg fatigue.

Adult↗

Patients supported for over 4 years with left ventricular assist devices.

Ventricular assist device implantation has become an established therapy in adults and children for bridging to heart transplantation or to aid myocardial recovery. Recently, implantation of left ventricular assist devices as definitive therapy has been recognized as a better option than pharmacological treatment in patients who are not candidates for heart transplantation. This study presents our institution's experience with five patients successfully supported by two different left ventricular assist devices for over 4 years. This unique experience shows that left ventricular assist device support can be extended beyond 4 years with good quality of life and low risk, making it a good alternative for non-transplant candidates.

Adult↗

Advances in the medical treatment of pulmonary hypertension.

Increased pulmonary precapillary vascular resistance due to vasoconstriction and vasoproliferative processes is the basic pathophysiological mechanism in the development of pulmonary hypertension (PH). With the exception of pulmonary venous hypertension, where the primary cause of PH is left ventricular failure or mitral valvular disease, all the other PH categories will benefit to a greater or lesser extent from pulmonary vasodilator and antivasoproliferative therapy. Today, for this purpose, in addition to intravenous prostacyclin (epoprostenol), which is restricted to severe pulmonary arterial hypertension (NYHA class IV and late class III), other therapeutic options such as treatment with more stable prostacyclin analogs (oral beraprost, aerosolized iloprost), endothelin-receptor antagonists (bosentan) or phosphodiesterase inhibitors (sildenafil) are also available and these are especially useful for the treatment of the early stages of the disease. The recent progress in medical therapy has markedly increased the life expectancy in patients with pulmonary arterial hypertension and substantially improved their quality of life. Chronic hemodialysis (HD) patients show higher endothelin-1 (ET-1) activity in comparison to healthy individuals and there is evidence that the increase of pulmonary vascular resistance in these patients is at least in part mediated by ET-1. Recent data show good results after PH therapy with the endothelin-receptor antagonist bosentan in HD patients. Also prostacyclin and its analogs, as well as phosphodiesterase inhibitors, can be useful for the treatment of pulmonary hypertension in patients with chronic renal failure.

Antihypertensive Agents↗

Genetic and phenotypic analysis of dilated cardiomyopathy with conduction system disease: demand for strategies in the management of presymptomatic lamin A/C mutant carriers.

BACKGROUND: One-third of cases of dilated cardiomyopathy (DCM) is of familial aetiology. Several genes have been reported to cause the autosomal dominant form of DCM. AIMS: To analyze the lamin A/C gene (LMNA) in 31 unrelated patients with DCM and conduction system disease (CSD). METHODS: Patients and family members underwent physical examination, ECG/Holter-ECG, echocardiography, and selective coronary angiography. Genetic analysis of all coding exons of LMNA was performed using PCR and sequencing. RESULTS: Three different LMNA mutations (Arg377His, c.1397delA, c.424_425ins21nt) were identified in three families with autosomal dominant disease comprised of 39 individuals. 21 individuals were mutation carriers, of whom 12 were symptomatic. We observed a progressive and age-dependent form of DCM with CSD and arrhythmias. First, the patients developed a moderate left ventricular dilatation without symptoms. Later, systolic function declined progressively and the patients became symptomatic resulting in a high mortality due to sudden death and heart failure. CONCLUSIONS: Genetic screening leads to the identification of symptomatic and asymptomatic mutant carriers. The latter at a young age should be regarded as "presymptomatic" because of the age-dependent disease manifestation. New guidelines are required for the management of these individuals.

Adolescent↗

Thoracic aorta endografts: variations in practice among medical specialists.

BACKGROUND: Endovascular stent-graft placement is emerging as a novel treatment option for patients with diseases of the descending thoracic aorta. However, currently no consensus guidelines exist to direct uniformity in stent-graft procedures as well as for pre- and postprocedural patient management, unlike that for the management of other cardiovascular disorder. Accordingly, the aim of the present survey was to assess variations in thoracic aortic stent-graft practice among different subspecialties in Germany. METHODS: An interdisciplinary questionnaire survey was conducted among 206 departments of vascular surgery, radiology, cardiology, and cardiothoracic surgery in Germany that actively performed aortic stent-graft placement. Data on preoperative procedure planning, logistics, practical/technical issues of stent-graft placement, and postoperative patient management were evaluated using a standardized, self-administered questionnaire comprising 29 items. Responses were tabulated for analysis. RESULTS: Of a total of 206 questionnaires, 184 (89.3%) were returned with 71 (38.5%) centers reporting to have performed thoracic aortic stent-graft placement (total number of procedures 2,267) through 1997 and 2003. The average number of stent-graft procedures per year was 7.4 (25-75% percentile, 2.05-10.75) at participating sites, with 49% of the respondents reporting <5 procedures per year. Treatment of thoracic aortic aneurysms was the predominant indication for stent-graft placement, followed by type B-dissection. As anticipated, marked variability existed among the different medical specialties performing stent-graft procedures with respect to all aspects of the procedures including indication for treatment, choice of preoperative and intraoperative imaging modalities, technical equipment and perioperative management. The only consistent agreement was on the need for lifelong follow-up after stent-graft placement, with CT being the preferred imaging technique (90% of centers). CONCLUSION: The present survey documents an increasing adoption of endovascular stent-graft placement for patients with diseases of the descending thoracic aorta in Germany. Despite this, there is a lack of consensus among the different medical specialties performing stent-graft placement with respect to indications and technical execution of stent-grafting. Our data supports the need for consensus practice guidelines endorsed by medical professional societies for stent-graft procedure to standardize the growing number of thoracic stent graft procedures.

Angioplasty↗

Metastasizing testicular germ-cell tumor with infiltration of the right heart: indication for primary metastasectomy.

Cardiac intracavitary metastases are very uncommon. The case of a 42-year-old male patient with a testicular germ cell tumor extending into the superior caval vein, the left brachiocephalic vein, and the right heart, which manifested as a mild form of pulmonary embolization, is presented. Due to the perceived high risk of continuous embolization and the urgent need to begin systemic chemotherapy, a complete cardiac tumor resection was performed, utilizing a cardiopulmonary bypass, followed by a simultaneous orchiectomy. Histology revealed a 61-cm long vascular tumor as a metastasis of a yolk sac tumor originating from the left testis. There were no postoperative complications, and the patient is alive and without tumor recurrence 12 months after four cycles of systemic chemotherapy according to the PEB (cisplatin, etoposide, bleomycin) scheme. We conclude that in this special case aggressive surgical management following chemotherapy was very effective in controlling the disseminated testicular tumor.

Adult↗

Role of ventricular assist devices in the German heart allocation system.

The Eurotransplant (ET) allocation algorithm, newly implemented in 2000, gives priority for heart transplantation (HTx) to patients with high urgency (HU) status, but now this status is rescinded upon ventricular assist device (VAD) implantation and only regained if severe complications occur during mechanical circulatory support (MCS). We studied the effects of this change on the patients in our institute who were waiting for HTx with MCS. The median duration of MCS until HTx in adult patients gradually increased from 3.1 months in 1994, reaching a peak of 16.7 months in 2000, and then gradually decreased to 6.0 months in 2003. Among the patients with VAD implantation as a bridge to HTx, two patients were on MCS for more than 1 year (the longest duration of MCS being 1.6 years) at the end of 1999, and this figure increased to nine patients and a maximum MCS duration of 3.7 years at the end of 2003. These data imply that the patients in whom a complication occurred in the early phase of MCS and who had overcome this complication underwent HTx early with HU status, and those who were stable during MCS waited a long time for HTx. Furthermore, the number of patients in the latter group is increasing. The new allocation algorithm imposes on patients with MCS waiting for HTx who are relatively young and free from complications and serious coexisting disease, very long-term MCS without an end to VAD bridging, which is almost equivalent to destination therapy.

Algorithms↗

Arteriolar blood flow pulsatility in a patient before and after implantation of an axial flow pump.

In a patient with end stage ischemic heart failure scheduled for implantation of an axial flow pump small arteriolar flow pattern was recorded using a novel intravital microscope. Preoperative arteriolar blood flow velocity was highly pulsatile, ranging from about 7 to 16 mm per second in a 12.8 microm diameter arteriole. After implantation of the pump, this pulsatility was abrogated and arteriolar blood flow velocity changed instantaneously with changes in pump speed (eg, 2 mm/s at 5,000 rpm vs 3.5 mm/s at 8,000 rpm in an 8.9 microm diameter arteriole). This lack of flow velocity oscillations may have profound long-term effects on shear stress regulated arteriolar remodeling.

Arterioles↗

In vitro fabrication of a tissue engineered human cardiovascular patch for future use in cardiovascular surgery.

BACKGROUND: One approach to tissue engineering has been the development of in vitro conditions for the fabrication of functional cardiovascular structures intended for implantation. In this experiment, we developed a pulsatile flow system that provides biochemical and biomechanical signals in order to regulate autologous, human patch-tissue development in vitro. METHODS: We constructed a biodegradable patch scaffold from porous poly-4-hydroxy-butyrate (P4HB; pore size 80 to 150 microm). The scaffold was seeded with pediatric aortic cells. The cell-seeded patch constructs were placed in a self-developed bioreactor for 7 days to observe potential tissue formation under dynamic cell culture conditions. As a control, cell-seeded scaffolds were not conditioned in the bioreactor system. After maturation in vitro, the analysis of the tissue engineered constructs included biochemical, biomechanical, morphologic, and immunohistochemical examination. RESULTS: Macroscopically, all tissue engineered constructs were covered by cells. After conditioning in the bioreactor, the cells were mostly viable, had grown into the pores, and had formed tissue on the patch construct. Electron microscopy showed confluent smooth surfaces. Additionally, we demonstrated the capacity to generate collagen and elastin under in vitro pulsatile flow conditions in biochemical examination. Biomechanical testing showed mechanical properties of the tissue engineered human patch tissue without any statistical differences in strength or resistance to stretch between the static controls and the conditioned patches. Immunohistochemical examination stained positive for alpha smooth muscle actin, collagen type I, and fibronectin. There was minor tissue formation in the nonconditioned control samples. CONCLUSIONS: Porous P4HB may be used to fabricate a biodegradable patch scaffold. Human vascular cells attached themselves to the polymeric scaffold, and extracellular matrix formation was induced under controlled biomechanical and biodynamic stimuli in a self-developed pulsatile bioreactor system.

Absorbable Implants↗

Detection of lower torso ischemia by near-infrared spectroscopy during cardiopulmonary bypass in a 6.8-kg infant with complex aortic anatomy.

Neonates and small infants with congenital heart disease and complex cardiac and vascular anatomy are particularly prone to episodes of complete or incomplete regional ischemia during cardiopulmonary bypass. These episodes may result either from inhomogeneous distribution of arterial blood flow via the aortic cannula or from impaired drainage of blood via the venous cannulae. However, techniques for continuous routine monitoring of regional perfusion in neonates or small infants undergoing cardiopulmonary bypass are extremely limited. Over recent years, transcranial near-infrared spectroscopy has become established as a useful technique for the non-invasive monitoring of cerebral oxygenation. Here we present a case in which simultaneous near-infrared spectroscopic monitoring of the oxygenation status in the brain and the right upper thigh revealed lower torso ischemia due to accidental cross-clamping of a hypoplastic descending aorta which would otherwise have been unnoticed. This shows that parallel near-infrared spectroscopy of the brain and the lower extremities may represent a novel non-invasive monitoring technique to ensure adequate cerebral and extracerebral perfusion during cardiopulmonary bypass.

Aorta, Thoracic↗

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

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

Actins↗

Improvement in survival after mechanical circulatory support with pneumatic pulsatile ventricular assist devices in pediatric patients.

BACKGROUND: Pediatric size pneumatically driven extracorporeal ventricular assist devices (VAD) for infants and small children were introduced into clinical routine in 1992. In the initial period, the results in infants were poor. Since then, several improvements have been introduced with regard to the cannulas, connectors, heparin coating of the blood pump inner surface, anticoagulant treatment and coagulation monitoring, and earlier decision-making in favor of pump implantation before irreversible shock has set in. METHODS: Since 1990 and as of January 1, 2005, 62 Berlin Heart Excor systems have been implanted in patients below 18 years of age at our institution. The patients were divided into two groups according to the period of treatment: period 1, devices implanted between 1990 and 1998 (n = 34), and period 2, devices implanted between 1999 and 2004 (n = 28). We compared our experience during the earlier and later periods. RESULTS: There were no significant differences in the preoperative patient data between the two periods except for time of support (17.9 +/- 27.7 days versus 53.2 +/- 83.9 days, p = 0.001). In period 1, more patients needed a biventricular VAD whereas in period 2, more patients were effectively treated with a left VAD (p = 0.05). In the later period, the chest could be primarily closed in a significantly higher percentage of infants (0% versus 89%, p = 0.012), and more infants could be extubated on the VAD (0% versus 55%, p = 0.16). Discharge from the hospital after either weaning from the system or heart transplantation was achieved for 35% in period 1 and for 68% in period 2 (p = 0.029). Whereas in period 1 there were no survivors in the group of children younger than 1 year old, during period 2, survival in this age group was similar to that of the two groups of older children (p = 0.024). There was a significant improvement in the discharge rate in period 2 in patients with cardiomyopathy (43% versus 76%, p = 0.045) and postcardiotomy heart failure (0% versus 57%, p = 0.01). CONCLUSIONS: Earlier implantation of VADs, heparin coating of the blood pumps, and substantial modifications in cannula design, anticoagulation, and the coagulation monitoring regimen have led to a significant increase in the survival and discharge rate, especially among children under 1 year of age. The pediatric size Berlin Heart Excor VAD is a valuable option as a bridge to heart transplantation or recovery for children suffering from cardiogenic shock.

Adolescent↗

Relevance of depth resolution for cerebral blood flow monitoring by near-infrared spectroscopic bolus tracking during cardiopulmonary bypass.

OBJECTIVE: Noninvasive near-infrared spectroscopy (NIRS) is increasingly used to monitor cerebral oxygenation and blood flow status, which is also of high relevance during cardiovascular surgical interventions with cardiopulmonary bypass. Contamination of the cerebral signal by contamination from overlaying extracerebral tissue, however, has been proposed to reduce sensitivity and cerebral selectivity of this promising technique. METHODS: We evaluated a novel depth-resolved approach for the determination of cerebral hemodynamics by near-infrared spectroscopic tracking of intravenously administered indocyanine green boluses. A frequency domain technique was applied, allowing simultaneous determination of light absorption changes and time of flight of single photons and enabling the differentiation between extracerebral and intracerebral tracer kinetics. Depth-resolved near-infrared spectroscopy was tested in 4 patients undergoing cardiopulmonary bypass and compared with data derived by conventional continuous-wave near-infrared spectroscopy. RESULTS: Depth resolution extracted the differential responses of extracerebral and intracerebral blood vessels from near-infrared bolus tracking signals. Postoperative blood flow indices derived from the intracerebral time course exceeded preoperative values by 1.5 +/- 0.2 times, indicating a significant increase of cerebral blood flow not detectable by conventional near-infrared spectroscopy. CONCLUSION: The depth-resolved approach provides additional and relevant data for the interpretation of intraoperative cerebral perfusion during cardiothoracic surgery. The validity of this approach for patients with preexisting risk factors for cerebral hypoperfusion remains to be determined in larger clinical trials.

Aged↗