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Biomedical subjects

Roland Hetzer

Publications and source records attributed to Roland Hetzer.

At least 55 records · Page 3Linked to original sources
PubMed2005

Reduced oxidative stress in parallel to improved cardiac performance one year after selective removal of anti-beta 1-adrenoreceptor autoantibodies in patients with idiopathic dilated cardiomyopathy: data of a preliminary study.

Patients with idiopathic dilated cardiomyopathy (IDC) were treated with selective immunoadsorption to remove anti-beta 1-adrenoreceptor autoantibodies (anti-beta1A-AB). After one year, the effect on cardiac performance and oxidative stress was tested. Extracorporeal immunoadsorption of the whole IgG class in IDC patients for the removal of anti-beta1A-AB reduced oxidative stress in parallel to an improvement of cardiac performance. However, the non-specificity of IgG adsorption means that these beneficial effects cannot be attributed exclusively to anti-beta1A-AB removal. In an open clinical pilot study enrolling 8 patients with IDC prior to and one year after selective immunoadsorption of anti-beta1A-AB, plasma markers for oxidative stress--thiobarbituric acid-reactive substances (TBARS), lipid peroxides (LPO) and anti-oxidized low-density lipoprotein autoantibodies (anti-oxLDL-AB)--were measured in parallel to evaluation of the left ventricular function using conventional echocardiography and wall motion analysis by tissue Doppler imaging. After one year, TBARS (Wilcoxon test with bootstrapping simulation for paired data: 95% confidence interval of the P value 0.020 to 0.029) and anti-oxLDL-AB (P = 0.025 to 0.035) were decreased in parallel to an improvement of the peak systolic wall motion velocity (P = 0.006 to 0.01) and left ventricular ejection fraction (P = 0.002 to 0.02). For changes over the study period, a direct correlation with borderline significance (P = 0.076) was calculated for TBARS to the left ventricular diameter in the diastole. One year after selective immunoadsorption for anti-beta1A-AB removal, patients with ICD show a reduction in oxidative stress and a parallel improvement in cardiac performance.

Adsorption↗
PubMed2005

Transfusion-free complex cardiac surgery with cardiopulmonary bypass in a 3.55-kg Jehovah's Witness neonate.

Complex cardiac surgery using cardiopulmonary bypass normally requires the transfusion of autologous blood components, particularly in neonates. This is predominately caused by the relatively high priming volume of the circuit with subsequent extreme hemodilution and the often extended and complex perfusions leading to progressive consumption of platelets and coagulation factors. We report on a strategy to minimize the cardiopulmonary bypass circuit and adjust the perfusion technique that resulted in transfusion-free correction of tetralogy of Fallot with an absent pulmonary valve and an aneurysm of the left pulmonary artery in a 3.55 kg Jehovah's Witness neonate boy.

Aneurysm↗
PubMed2005

Paralysis of the phrenic nerve as a risk factor for suboptimal Fontan hemodynamics.

OBJECTIVE: The introduction of the Fontan operation for single ventricle physiology was based on the dual principle of the pulmonary blood flow. It is postulated that normal breathing movements are necessary for passive blood flow into the lungs. We compared patients with and without palsy of the phrenic nerve regarding the sufficiency of Fontan hemodynamics. METHODS: We analyzed 85 consecutive patients, who were available for follow-up after completion of their total cavopulmonary connection (TCPC) between February 1992 and February 2003. The median age at TCPC completion was 4.3 (range 1.3-37) years. Sixty were operated on with an extracardiac conduit and 25 with a lateral tunnel. Fifty patients underwent postoperative heart catheterization with contrast angiography. The diagnosis of diaphragm paralysis was made using echocardiography, fluoroscopy and X-ray examination. Surgical diaphragm plication was performed in 13 patients (Four before and nine after Fontan operation) at a median of 2.2 years after the diagnosis. RESULTS: Twenty-one patients developed fixed palsy of the phrenic nerve during a total of 225 operations before and including completion of TCPC. There were no differences in the incidence of phrenic nerve paralysis between small children (aged <3 years) and older patients or between patients with the extracardiac and intracardiac Fontan procedures. There were no differences in the duration of mechanical ventilation. However, prolonged pleural effusions and a hospital stay of longer than 2 weeks were noted more frequently in patients with palsy (P<0.05). During the median follow-up of 4.6 (range: 0.7-11.4) years significantly more patients with phrenic nerve palsy developed chronic ascites compared to those without palsy (8 of 20 vs. 2 of 65; P<0.001). CONCLUSIONS: Phrenic nerve palsy was recognized as a risk factor for suboptimal Fontan hemodynamics due to the hindrance of passive venous blood flow. Patients with phrenic nerve palsy have a longer hospital stay and a higher incidence of prolonged pleural effusions and of chronic ascites, than those without. Early diaphragm plication may be favorable to optimize the Fontan circuit in these patients. Completion of the TCPC in patients with diaphragm paralysis should be viewed critically.

Adolescent↗
PubMed2005

Natriuretic peptides and E-selectin as predictors of acute deterioration in patients with inotrope-dependent heart failure.

OBJECTIVE: In patients with inotrope-dependent end-stage heart failure the timely application of the most suitable treatment, i.e. heart transplantation, implantation of a ventricular assist device or conservative treatment, is a key issue for therapeutic success. METHODS: Seventy-six inotrope-dependent patients with end-stage heart failure were enrolled. Measurements of hemodynamics, routine laboratory parameters, and clinical examination were performed daily. Additionally, natriuretic peptides (BNP and NT-proBNP) and E-selectin were measured at the end of the study. The patients were retrospectively divided into groups with regard to the following end-points: Group I-deterioration into cardiogenic shock after an initially stable clinical course (n=26); Group II-stable clinical course without deterioration into cardiogenic (n=41); Group III-weaning from inotropic support (n=9). RESULTS: One day before cardiogenic shock occurred, BNP, NT-proBNP and E-selectin were significantly elevated in group I compared with group II. A logistic regression model showed that only BNP and E-selectin were independent predictors of clinical deterioration on the following day. The odds ratio (OR) for E-selectin using a cut-off point of 65ng/ml was 8.7 and for BNP using a cut-off of 500pg/ml it was 4.8. In combination, the OR increased to 11.1. Continuous decrease of NT-proBNP predicted patients in whom weaning from inotropes was possible. CONCLUSIONS: While routine parameters did not predict the clinical course, elevated BNP and E-selectin independently predicted cardiogenic shock on admission and 1 day before its occurrence. The combination showed increased predictive value.

Adolescent↗
PubMed2005

Does size matter? Larger Blalock-Taussig shunt in the modified Norwood operation correlates with better hemodynamics.

OBJECTIVE: Excess pulmonary to systemic blood flow ratio (Qp/Qs) correlates with hemodynamic instability and mortality after modified Norwood operation. Studies suggest that maximal oxygen delivery occurs at a Qp/Qs of around 1. The use of a rather small modified Blalock-Taussig shunt (MBTS) is believed to achieve this goal. However, optimal MBTS size with respect to postoperative hemodynamics remains unclear. METHODS: Between 2/2002 and 2/2004, 20 consecutive patients underwent Norwood operation; there were 19 operative survivors: nine with a normalized MBTS area (NSA) > or = 3.3 mm2/kg (group 1) and 10 with NSA < 3.3 mm2/kg (group 2). Mean arterial pressure (MAP) and common atrial pressures (CAP), arterial and superior vena cava oxygen saturations, urinary output and inotropes recorded for the postoperative hours 0, 6, 12, 18, 24 and 48 were analyzed. RESULTS: Hospital mortality was 11.1% (1/9) in group 1 and 30% (3/10) in group 2 (P = 0.6). For group 1 significantly higher MAP of 52+/-1.3 versus 46+/-0.8 mmHg (P < 0.001), higher urinary output of 6.2+/-0.5 versus 4.2+/-0.5 ml/kg per h (P < 0.01), lower CAP of 8+/-0.3 versus 10+/-0.4 mmHg (P < 0.001), and lower heart rate of 145+/-2.6 versus 160+/-1.6 bpm were recorded than for group 2. In group 1, lower doses of adrenaline (0.03+/-0.01 versus 0.15+/-0.01 microg/kg per min, P < 0.05) and noradrenaline (0.01+/-0.01 versus 0.13+/-0.04 microg/kg per min, P < 0.01) were needed. Although Qp/Qs was more often calculated to be > 1.5 in group 1 (51 versus 31%), arteriovenous oxygen difference and oxygen excess factor were not significantly different, indicating similar oxygen delivery. CONCLUSIONS: Monitoring of the central venous oxygen saturations and application of afterload reduction in cases of high Qp/Qs allows the insertion of a larger MBTS without association with lower oxygen delivery. In fact, better hemodynamic status with less inotropic support was noted with a larger MBTS early after Norwood operation.

Anastomosis, Surgical↗
PubMed2005

Pneumatic pulsatile ventricular assist devices in children under 1 year of age.

OBJECTIVE: Although considerable progress has been made on ventricular assist devices (VAD) for adults, pneumatic pulsatile circulatory support in young infants is still limited. There is a need for long-term ventricular assist devices to bridge the failing myocardium of young children until recovery or transplantation. Miniaturized devices and innovative modalities need to be optimized. We report on our experience. METHODS: From 1/1992 to 6/2004, 18 infants (6 male/12 female) under 1 year of age were treated with the Berlin Heart Excor VAD. The infants were divided into two groups, depending on the year of treatment. Group A consists of eight infants resuscitated and supported with a pulsatile pneumatic ventricular assist device between 1992 and 1998 and group B consists of 10 infants treated between 1999 and 6/2004. With the pediatric-sized Berlin Heart we used miniaturized extracorporeal pneumatically driven blood pumps, the lowest stroke volume being 10 ml. RESULTS: In 18 children, age 3-345 (median 147) days, artificial replacement of heart function was applied for long-term support (1-64, median 10 days) as a life-saving measure in our hospital. Nine had LVAD and nine BVAD support. All were in cardiogenic shock with multiorgan failure; three had fulminant myocarditis, four cardiomyopathy, and one chronic stage of congenital heart disease. Five children were weaned from the system, three reached heart transplantation, and 10 died on the VAD. There were no differences between groups A and B regarding age, body weight or diagnosis, but the duration of mechanical support differed: Group A, median 2, range 1-16 days; group B, median 12, range 1-100 days. Since 1999 (group B), the survival rate of our small infants has increased to 70% whereas none of the infants in group A survived to be discharged. CONCLUSIONS: The outcome of VAD support in small infants is no longer inferior to that of adult support, now optimized cannulas, modified anticoagulation and optimized surgical and intensive care management have been established.

Anticoagulants↗
PubMed2005

Clinical experience with Certican (everolimus) in de novo heart transplant patients at the Deutsches Herzzentrum Berlin.

Immunosuppressant agents have greatly increased graft and overall survival in heart transplant patients, but some of these agents (e.g., calcineurin inhibitors [CNI] and corticosteroids) can also induce adverse events that may contribute to cardiac allograft vasculopathy (CAV) (e.g., nephrotoxicity and cytomegalovirus infection). The current trend is therefore toward CNI- and steroid-sparing regimes. This study reports on the initial clinical experience with Certican (everolimus), a novel proliferation signal inhibitor with immunosuppressant properties that has been shown to prevent or delay CAV. Seven de novo heart transplant patients were treated at our center. Patients received cyclosporine for microemulsion (CsA; Neoral), corticosteroids and fluvastatin in addition to everolimus. Mean everolimus blood trough levels were maintained within the target range of 3 to 8 ng/ml throughout the first 14 weeks post-transplant. CsA was initiated at a reduced dose, and by Weeks 8 to 14 the mean trough blood level was 187.7 ng/ml. The combination of everolimus and reduced-dose CsA was not associated with increased incidence of biopsy-proven acute rejection (BPAR). Two patients did experience BPAR, but only very mildly (ISHLT Grade 1A). The mean creatinine level pre-transplant was 1.5 mg/dl; this increased to 2.0 mg/dl at 2 weeks post-transplant, but returned to near baseline levels during Weeks 8 to 14 (1.66 mg/dl). Some patients had elevated blood lipids. Patients receiving everolimus should have lipid levels monitored on a regular basis. Everolimus may allow optimization of immunosuppressant regimens in de novo heart transplant patients so that adequate efficacy can be achieved with reduced CNI exposure, thereby protecting kidney function.

Cyclosporine↗
PubMed2005

Reversibility of cardiac cachexia after heart transplantation.

BACKGROUND: Cachexia is an independent risk factor for mortality in patients with chronic heart failure and increases mortality even after heart transplantation (HTx). We aimed to determine whether cardiac cachexia is reversible after HTx, and investigated differences specific to gender. METHODS: We prospectively examined 106 patients before and serially 3, 6, 12 and 24 months after HTx (18 women, 88 men; median age at transplantation 53.7 +/- 9.7 years; n = 68 dilative cardiomyopathy, n = 33 coronary heart disease, n = 5 other origin of heart failure). Patients were sub-grouped as underweight (body mass index [BMI] < or =21 kg/m2, n = 15), normal weight (BMI 21 to 27 kg/m2, n = 64) and obese (BMI > or =27 kg/m2, n = 27). RESULTS: Body weight increase was restricted to underweight patients: at 3 months (+6.8% vs pre-transplant weight); at 6 months (+11.3%), at 12 months (+15.6%); and at 24 months (+17.7%, all p < or = 0.03). The entire population had weight loss at 3 months (-2.9%), but had weight gain at 6 (+2.5%), 12 (+6.1%, all p < or = 0.02) and 24 months (+1.3%, p = 0.44). A lower BMI before HTx correlated significantly with greater weight increase after HTx at every follow-up time-point (r = 0.55; p < 0.001). There were no gender-specific differences for BMI or weight change. Weight loss within 3 months after HTx was associated with higher mortality during 4 years of follow-up. CONCLUSIONS: Weight gain after HTx is particularly strong in underweight patients, and the increased cardiac function causes the cessation of cachexia. The weight increase of the entire heart transplant population is partially an effect of reversibility of cachexia and not affected by gender.

Adolescent↗
PubMed2005

Assessment of hemostatic activation during cardiopulmonary bypass for coronary artery bypass grafting with bivalirudin: results of a pilot study.

OBJECTIVE: Bivalirudin has been successfully used as a replacement for heparin during on-pump coronary artery bypass grafting. This study was conducted to assess the effects of the currently suggested protocol for bivalirudin on hemostatic activation during cardiopulmonary bypass with and without cardiotomy suction. METHODS: Ten patients scheduled for coronary artery bypass grafting were enrolled. Bivalirudin was given with a bolus of 50 mg in the priming solution and 1.0 mg/kg for the patient, followed by an infusion of 2.5 mg . kg(-1) . h(-1) until 15 minutes before the conclusion of cardiopulmonary bypass. Cardiopulmonary bypass was performed with a closed system in 5 patients with and in 5 patients without the use of cardiotomy suction. Blood samples were obtained before and after cardiopulmonary bypass. D-dimers, fibrinopeptide A, prothrombin 1 and 2 fragments, thrombin-antithrombin, and factor XIIa were determined. RESULTS: Values for factor XIIa remained almost unchanged in both groups, indicating a minor effect of contact activation. In patients without cardiotomy suction, post-cardiopulmonary bypass values for D-dimers, fibrinopeptide A, prothrombin 1 and 2 fragments, and thrombin-antithrombin were not significantly increased compared with pre-cardiopulmonary bypass values. In patients with cardiotomy suction, values obtained for these parameters had significantly increased compared with pre-cardiopulmonary bypass values and the values obtained in the group without cardiotomy suction after cardiopulmonary bypass. CONCLUSIONS: With this protocol, hemostatic activation during cardiopulmonary bypass was almost completely attenuated when cardiotomy suction was avoided. Cardiotomy suction results in considerable activation of the coagulation system and should therefore be restricted and replaced by cell saving whenever possible.

Aged↗
PubMed2005

Prediction of cardiac function after weaning from ventricular assist devices.

OBJECTIVE: We analyzed the factors influencing the cardiac function of patients after weaning from ventricular assist devices and established a prognostic index. METHOD: A multivariate analysis was performed using the Cox proportional hazards model of the clinical parameters of 28 patients with end-stage heart failure before implantation of a ventricular assist device and directly before weaning from the device. RESULTS: After weaning from the ventricular assist devices, 14 of the 28 investigated patients showed stable cardiac function, and 12 had recurrent heart failure, but only 1 of them died before transplantation or implantation of another ventricular assist device, and 2 patients died of causes unrelated to heart failure. In addition to left ventricular ejection fraction, the duration of symptomatic heart failure and left ventricular intracavitary dimensions in diastole measured before ventricular assist devices weaning were the major factors influencing cardiac function after weaning. In the group of patients with heart failure duration less than 3 years, only 2 of 13 cases were recurrent, but in the group with heart failure duration more than 3 years, 10 of 15 cases were recurrent. In 10 patients with 40 to 50 mm left ventricular intracavitary dimensions in diastole before weaning, only 1 case was recurrent. In 10 patients with 51 to 55 mm left ventricular intracavitary dimensions in diastole, 3 cases were recurrent. In the group with left ventricular intracavitary dimensions in diastole more than 56 mm, all 8 cases were recurrent. A prognostic index was calculated using the following formula: prognostic index = -10.10 + 0.208 (heart failure duration in years) + 0.173 (pre-explantation left ventricular intracavitary dimensions in diastole in millimeters). In the group with a prognostic index less than 0, only 2 of 16 cases were recurrent, and the rate of stable cardiac function in the 51st month after weaning was 83.6%. In the group with a prognostic index greater than 0, 10 of 12 cases were recurrent, and the rate of stable function in the 57th month was 0.0%. CONCLUSION: In patients with off-pump left ventricular ejection fraction greater than 40%, the duration of symptomatic heart failure and the left ventricular intracavitary dimensions in diastole measured before weaning yield a useful index to predict long-term cardiac function after weaning from ventricular assist devices.

Device Removal↗
PubMed2005

Ahnak is critical for cardiac Ca(V)1.2 calcium channel function and its beta-adrenergic regulation.

Defective L-type Ca2+ channel (I(CaL)) regulation is one major cause for contractile dysfunction in the heart. The I(CaL) is enhanced by sympathetic nervous stimulation: via the activation of beta-adrenergic receptors, PKA phosphorylates the alpha1C(Ca(V)1.2)- and beta2-channel subunits and ahnak, an associated 5643-amino acid (aa) protein. In this study, we examined the role of a naturally occurring, genetic variant Ile5236Thr-ahnak on I(CaL). Binding experiments with ahnak fragments (wild-type, Ile5236Thr mutated) and patch clamp recordings revealed that Ile5236Thr-ahnak critically affected both beta2 subunit interaction and I(CaL) regulation. Binding affinity between ahnak-C1 (aa 4646-5288) and beta2 subunit decreased by approximately 50% after PKA phosphorylation or in the presence of Ile5236Thr-ahnak peptide. On native cardiomyocytes, intracellular application of this mutated ahnak peptide mimicked the PKA-effects on I(CaL) increasing the amplitude by approximately 60% and slowing its inactivation together with a leftward shift of its voltage dependency. Both mutated Ile5236Thr-peptide and Ile5236Thr-fragment (aa 5215-5288) prevented specifically the further up-regulation of I(CaL) by isoprenaline. Hence, we suggest the ahnak-C1 domain serves as physiological brake on I(CaL). Relief from this inhibition is proposed as common pathway used by sympathetic signaling and Ile5236Thr-ahnak fragments to increase I(CaL). This genetic ahnak variant might cause individual differences in I(CaL) regulation upon physiological challenges or therapeutic interventions.

Animals↗
PubMed2005

Small vessel disease after heart transplantation: impact of immunologic and nonimmunologic risk factors.

To determine risk factors for small vessel disease after heart transplantation (HTx), characteristics of donors and organ harvesting were evaluated in 246 HTx patients (205 male, 41 female, mean survival 5.4 years). In right ventricular endomyocardial biopsies (EMB, n = 5421) evidence of microvascular disease [endothelial cell (EC) swelling/vessel wall thickening] was evaluated by light microscopy (hematoxylin and eosin staining, x 200). Mild EC swelling/vessel wall thickening were found in 204 and 213 patients, severe EC swelling/vessel wall thickening were present in 23 and 142 patients respectively. Evidences of mild and severe acute cellular rejection were found in 2064 and 421 EMB respectively. Microvascular disease was positively correlated with mild acute rejection episodes (P < 0.05). EC swelling was more frequent in patients with donors dying of craniocerebral trauma. No correlations were present to further demographical data. Microvascular alterations after HTx seem to be the result of an immunologic conflict rather than to depend on nonimmunologic factors.

Adult↗
PubMed2005

The more closed the bypass system the better: a pilot study on the effects of reduction of cardiotomy suction and passive venting on hemostatic activation during on-pump coronary artery bypass grafting.

Cardiac surgery with cardiopulmonary bypass (CPB) leads to a powerful activation of the hemostatic system. We assessed to what extent this activation can be attenuated by comparing three different perfusion regimens for on-pump coronary artery bypass grafting (CABG): 1) use of a closed CPB system with aspiration of blood from the operation field via the cardiotomy suction line and active venting of the heart via a roller pump; 2) use of a closed CPB system avoiding aspiration of blood from the operation field via the cardiotomy suction line, but with active venting of the heart; and 3) use of a closed system, avoidance of aspiration of blood from the operation field via the cardiotomy suction line and with passive venting of the heart into the collapsible venous reservoir. Our data show that avoidance of aspiration of blood via the cardiotomy suction line significantly reduces hemostatic activation during on-pump CABG. However, further attenuation of hemostatic activation can be achieved by further closing the system and minimizing the blood/air interface by passive venting of the heart.

Blood Coagulation↗
PubMed2005

Seventeen-year clinical results of 1,037 Mitroflow pericardial heart valve prostheses in the aortic position.

BACKGROUND AND AIM OF THE STUDY: It is generally believed that the pericardial tissue valve is associated with a greater propensity to early structural failure and subsequent valve-related complications. However, a modified valve design during recent years has considerably improved the clinical durability of this bioprosthesis. METHODS: Between April 1986 and December 2003, single Mitroflow pericardial valve prostheses were inserted in the aortic position in 1,037 patients (mean age 72.4 +/- 8.4 years). Coronary artery bypass grafting (CABG) was performed in 373 patients (36%). Preoperative echocardiographic findings of structural valve deterioration (SVD) were confirmed at reoperation. Total follow up was 5,022 patient-years (pt-yr) (mean 4.85 +/- 4.7 years) and was 99.7% complete (three patients lost). RESULTS: Early (30-day) mortality was 2.9% for elective surgery; 434 patients (41.9%) died during the follow up period. Actuarial survival at 17 years was 23.2 +/- 2%. Actuarial freedom from valve-related mortality at 17 years was 92.0 +/- 2.2%, whereas the linearized mortality rate was 0.4%/pt-yr. Linearized valve-related complications occurred at a rate of 3.6%/pt-yr (n = 122). SVD of Mitroflow bioprostheses occurred at a rate of 1.0%/pt-yr, and caused stenosis (36.7%), insufficiency (20.4%) and combined stenosis and insufficiency (42.9%). Actual freedom from SVD at 17 years was 95.3 +/- 0.7% for all patients, 96.2 +/- 0.6% for those aged > 60 years, and 99.0 +/- 0.4% for those aged > 70 years. CONCLUSION: The Mitroflow pericardial bioprosthesis, in the aortic position, provides an excellent clinical performance and a low rate of valve-related morbidity, mortality and reoperation for up to 17 years. The prosthesis also demonstrates satisfactory hemodynamic performance, and is therefore recommended for patients aged > or = 70 years and for those aged 60-69 years with comorbidities.

Adult↗