Impact of cyclosporine on cardiac transplantation in Berlin.
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Biomedical subjects
Publications and source records attributed to R Hetzer.
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BACKGROUND: The role of B cells and macrophages in microvascular disease after heart transplantation remains controversial. METHODS: Out of a total of 809 endomyocardial biopsies without evidence of acute cellular rejection (n = 422, 72 females and 350 males, median age 46 years), 393 without evidence of the quilty phenomenon were investigated zero to ten years after heart transplantation. Vascular reaction (endothelial cell swelling and vessel wall thickening) was graded by H&E staining, and immunohistochemistry was performed for T cells (clone UCHL1), B cells (clone L26) and macrophages (clone KP1) and evaluated semi-quantitatively (light microscopy x 200). RESULTS: Positive reaction for T cells and macrophages as well as evidence of endothelial cell swelling decreased with time after heart transplantation. Positive reactions for B cells were less frequent and increased slightly during the observation time, while vessel wall thickening dominated the last observation interval between the fourth and tenth years. Severity of vascular reaction was independent of immunohistochemical evidence of B cells or macrophages. CONCLUSIONS: While activation of the humoral and the non-specific immunological system is common after heart transplantation, microvascular alterations seem to develop independently of these findings.
UNLABELLED: Between August 1989 and July 2003 14 Jehovah's Witness children with congenital heart defects (CHD) aged under 14 years (median 2.9 years) and with a median weight of 14 kg underwent 16 operations with cardiopulmonary bypass (CPB). Five children had been operated on previously between one to three times. Preoperatively, 7 children were prepared with oral iron supplementation and 10 received erythropoietin. Mean hemoglobin (Hb) at admission was 14.4 g/dl (range 10.9 - 19.2). The cardiopulmonary bypass (CPB) circuit was modified to reduce total priming volume. High doses of aprotinin were administered. The modified ultrafiltration (MUF) circuit, used in 7 patients, was parallel to the ECC circuit with continuous circulation of the blood through a small shunt between the arterial and venous lines. Operations performed consisted of VSD closure (3 pts.), ASD closure (3 pts.), Fontan operation (2 pts.), and complete AV canal correction, aortic commissurotomy, Ross operation, Glenn shunt, cor triatriatum correction, MV reconstruction combined with left outflow tract stenosis resection, correction of absent pulmonary valve syndrome, and correction of tetralogy of Fallot in one patient each. There were no deaths. Mean duration of CPB was 192 min and mean aortic cross-clamp time 40 min. The Hb value at the end of the operation was 4.9 - 14.5 g/dl (mean 9.6) and at discharge it was 7.1 - 14.5 g/dl (mean 15.5). No blood or blood products were used in any patient. CONCLUSION: Bloodless cardiac surgery with and without CPB can be safely performed in Jehovah's Witness infants and children.
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AIM: Graft vessel disease (GVD) is one of the main limiting factors to long-term survival after adult heart transplantation (HTx). The incidence of epicardial and microvascular GVD in paediatric patients was studied. METHODS: A total of 137 coronary angiographies from 130 paediatric HTx and heart and lung transplant (HLTx) patients (70 male, 60 female, aged 0-18 y) were evaluated according to the Stanford classification and its supplements (minor vessel alterations). In H&E stainings from right ventricular endomyocardial biopsies (EMB = 397), light microscopic diagnosis of acute cellular rejection (ISHLT classification) and vascular reaction (morphology of endothelial cells and vessel walls) was performed. RESULTS: Moderate rejection was present in 32.8% and severe rejection in 13.3% of EMB. Microvascular EC swelling was found in 33.5% and vessel wall thickening in 53.8% of EMB. The results of the coronary angiographic investigations were: Stanford lesions = 61.2%, peripheral obliterations = 52.5%, diameter fluctuations = 86.3%, pathologic tapering = 64.0%, calcifications = 10.8%. Long-term survivors (> or =5 y) showed macrovascular alterations in 78% of cases and microvascular alterations in 67% of cases. CONCLUSION: The development of micro- and macrovascular GVD is one of the predominant complications in long-term survivors after paediatric HTx and HLTx.
Gender differences in the syndrome of heart failure (HF) occur in etiology and pathophysiology and lead to differences in the clinical presentation and course of the syndrome. In addition, gender specific treatment responses and gender associated differences in the behavior of treating physicians are found. Hypertension and diabetes play a major role as causes of HF in women and both interact in their pathophysiology with the renin angiotensin system (RAS). Modulation of the RAS by estrogens explains specific differences between pre- and post-menopausal women and men. Myocardial growth processes and myocardial calcium handling are differentially regulated in female and male myocytes. Myocardial remodeling with age and as a consequence of mechanical load differs in women and men. For yet unknown reasons, HF with preserved systolic function seems to be more frequent in women than in men and the clinical course of systolic HF is different in both genders. Medical therapy in heart failure has usually not been specified according to gender and gender specific analysis has been neglected in most large survival trials. Only a post-hoc analysis of gender differences led to the recognition of increased mortality with digitalis therapy in women. Single studies on angiotensin converting enzyme inhibitors (ACEI) or beta-receptor blockers did not reach significant end points in women whereas meta-analyses showed overall positive effects. Side effects of ACEI are more common and pharmacokinetics of beta-blockers are different in women. Angiotensin receptor blockers (ARB) are equally well tolerated in women and men. RAS inhibition may be particularly advantageous in postmenopausal women in whom the natural modulation of the RAS by estrogens is lost.
INTRODUCTION: Assessment of systolic and diastolic ventricular function in children and adults with morphologically and functionally univentricular heart is difficult using the conventional echocardiographic methods. Quantitative assessment of systolic and diastolic wall motion by TDE may provide information on abnormal systolic and diastolic ventricular function. Thus, the object of this study was to analyze the patterns of anterior and posterior wall motions in children with univentricular heart after palliative Fontan operation in comparison to normal subjects. PATIENTS AND METHODS: We investigated 21 patients of an average age of 10.1 years (range 4.2 to 32 years) with the primary diagnosis of univentricular heart and tricuspid atresia after a median period of 4.3 (range 1.2 to 8) years after cavo-pulmonary anastomosis (Fontan procedure) and in comparison to a normal collective of children without cardiovascular malformations. For investigation we used the novel tissue Doppler echocardiography (TDE) (EchoPack 6.3.6, Vingmed, Norway). Thereby we chose the standardized apical view and evaluated the left and right annular systolic (S(T)), early diastolic (E(T)) and atrial (A(T)) motion. We also registered the acceleration and deceleration time of each obtained curve. RESULTS: In comparison to the posterior myocardial wall the velocities at the anterior wall of the rudimentary ventricle were significantly reduced in all patients with tricuspid atresia and univentricular heart (p<0.0001). Particularly the annular systolic and diastolic wall motions of the rudimentary ventricle as well as their deceleration and acceleration time in patients with univentricular hearts differed significantly from those in healthy persons. CONCLUSION: Abnormal myocardial wall motion is detectable in children and adults with univentricular heart after palliative cardiac procedures using tissue Doppler echocardiography. The hemodynamic value of the measured abnormal wall motions, however, need further comparative studies.
Ebstein's anomaly is a rare congenital heart defect in which the hinges of the septal and/or posterior leaflets are displaced downward to the right ventricle. The anterior leaflet is usually not displaced but is enlarged and sail-like and valve closure is likewise displaced downwards. Since 1988 we have operated on 22 patients with Ebstein's anomaly using a modified repair technique of the tricuspid valve. This technique restructures the valve mechanism at the level of the true tricuspid annulus by using the most mobile leaflet for valve closure without plication of the atrialized chamber. We evaluated our long-term results with regard to functional capacity (New York Heart Association functional class), tricuspid valve function, rhythm disturbances and re-operation rate. We quantified the right ventricular function by measuring flow velocity integral of the pulmonary artery (VTIPA). All patients survived the operation. There were two hospital deaths (9%) and the late mortality was 4.5%. The mean followup period was 9 years (range, 1.5 to 13 years) for 19 patients. So far no re-operation has been necessary. Preoperatively, the majority of all patients were in NYHA classes III and IV (79%). After the first postoperative follow-up examination (2.9 months), 17 patients were in NYHA class II. Long-term follow-up examinations showed an additional improvement of 11 patients to NYHA class I. Echocardiographic studies demonstrated a significant improvement of tricuspid valve function. No tricuspid valve stenosis was observed. Significant improvement of VTI(PA) was observed. Analysis of the postoperative deaths demonstrated that all patients were in NYHA class III or IV and had a cardiothoracic ratio of 0.65 or more. A severe reduction in functional capacity seems to be an additional risk factor for mortality beside a cardiothoracic ratio greater than 0.65. We conclude that reconstruction of the tricuspid valve without ventricle plication not only achieves good functional results immediately after the operation but that follow-up examinations demonstrate stable or improved functional capacity in the long term. We postulate that incorporation of the atrialized chamber into the right ventricle may contribute to right ventricular contraction and thereby account for the improved functional capacity of the patients.
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AIMS: To directly compare the differential effects of oxygen, prostacyclin and iloprost (aerosolized and intravenous) in primary pulmonary hypertension. METHODS AND RESULTS: Twenty-one patients with severe primary pulmonary hypertension underwent right heart catheterization following oxygen inhalation, inhalation of aerosolized iloprost, intravenous prostacyclin or intravenous iloprost. The stability of the iloprost solution was tested for up to 4 weeks. Oxygen slightly decreased pulmonary vascular resistance. Intravenous prostacyclin (7.2+/-3.4 ng kg(-1) min(-1)) reduced pulmonary (1772+/-844 vs 1325+/-615 dyn s cm(-5), P<0.001) and systemic vascular resistance, and arterial and right atrial pressure, while cardiac output increased. Iloprost inhalation diminished pulmonary (1813+/-827 vs 1323+/-614 dyn s cm(-5), P<0.001) and systemic vascular resistance, and pulmonary artery (58+/-12 vs 50+/-12 mmHg,P<0.001) and right atrial pressure, while cardiac output increased. With intravenous iloprost (1.2+/-0.5 ng kg(-1) min(-1), n=8) a decrease in pulmonary (2202+/-529 vs 1515+/-356 dyn s cm(-5), P<0.05) and systemic vascular resistance and right a trial pressure occurred while cardiac output increased. Iloprost solution remained stable for 33 days while losing <10% (4 degrees C) of its active drug concentration.Conclusions Intravenous iloprost and prostacyclin have very similar haemodynamic profiles. In contrast, only inhaled iloprost exerted selective pulmonary vasodilation, reducing pulmonary vascular resistance and pulmonary artery pressure without systemic vasodilation. The longer half-life and extended stability despite lower costs render iloprost an attractive alternative to chronic prostacyclin treatment in primary pulmonary hypertension.
OBJECTIVE: Single ventricle palliation is rarely performed in adults and the results are less optimal than in children. In this article we analyze our experience with the modified Fontan operation in this age group. METHODS: Data of 15 consecutive patients with single ventricle with a mean age of 26 (range 16-38) years, who underwent Fontan operation between 3/92 and 1/2000 were retrospectively analyzed. Five patients had previously had an aortopulmonary shunt in childhood and two patients had previously received a bi-directional cavopulmonary shunt as adults. Eleven patients were preoperatively in NYHA class III and four in class II. The main factors for the selection of the patients before surgery were well-developed pulmonary arteries with lower lobe index 120+30 mm/m(2), pulmonary artery pressure <18 mmHg, good cardiac function and enddiastolic systemic ventricular pressure <12 mmHg. The lateral tunnel Fontan operation (LTFO) was performed in ten patients and extracardiac Fontan operation (ECFO) in five. A fenestration 4-5 mm in size was constructed in all patients with LTFO and in three of five patients with ECFO. RESULTS: There was one intraoperative and one late death (total mortality 13%). The mean extubation time and hospital stay were 24 h and 21 days, respectively. Severe postoperative complications were observed in three patients (20%). Two LTFO patients out of a total of eight patients (53%) with perioperative arrhythmias received a permanent pacemaker due to bradyarrhythmia. During the median follow-up of 5.0 (range 2.3-10.1) years, four patients developed arrhythmias; one of them had new onset bradyarrhythmia after LTFO and required permanent pacemaker implantation. The median postoperative oxygen saturation was 93% (range 90-98%). NYHA class improved significantly in 12 survivors. Cardiac catheterization (0.5-4 years postoperatively, n=12) showed excellent Fontan hemodynamics in all patients. CONCLUSIONS: The modified Fontan operation can be performed in adults with acceptable early and midterm mortality and morbidity and leads to either complete or marked relief of cyanosis and enhanced exercise tolerance in all survivors. Postoperative arrhythmias are one of the main drawbacks but the incidence of arrhythmias after ECFO seems to be lower. The long-term follow-up has yet to be established.
Defects in nine sarcomeric protein genes are known to cause hypertrophic cardiomyopathy (HCM). Mutation types and frequencies in large cohorts of consecutive and unrelated patients have not yet been determined. We, therefore, screened HCM patients for mutations in six sarcomeric genes: myosin-binding protein C3 (MYBPC3), MYH7, cardiac troponin T (TNNT2), alpha-tropomyosin (TPM1), cardiac troponin I (TNNI3), and cardiac troponin C (TNNC1). HCM was diagnosed in 108 consecutive patients by echocardiography (septum >15 mm, septal/posterior wall >1.3 mm), angiography, or based on a state after myectomy. Single-strand conformation polymorphism analysis was used for mutation screening, followed by DNA-sequencing. A total of 34 different mutations were identified in 108 patients: 18 mutations in MYBPC3 in 20 patients [intervening sequence (intron) 7 + 1G > A and Q1233X were found twice], 13 missense mutations in MYH7 in 14 patients (R807H was found twice), and one amino acid change in TPM1, TNNT2, and TNNI3, respectively. No disease-causing mutation was found in TNNC1. Cosegregation with the HCM phenotype could be demonstrated for 13 mutations (eight mutations in MYBPC3 and five mutations in MYH7). Twenty-eight of the 37 mutation carriers (76%) reported a positive family history with at least one affected first-grade relative; only eight mutations occurred sporadically (22%). MYBPC3 was the gene that most frequently caused HCM in our population. Systematic mutation screening in large samples of HCM patients leads to a genetic diagnosis in about 30% of unrelated index patients and in about 57% of patients with a positive family history.
After the first transplantation thirty-five years ago, heart transplantation has become an established and surgically widely standardized treatment modality for patients with end-stage heart failure. The improved medical therapy and alternative treatment options like revascularisation (CABAG), electrical resynchronization by a three-chamber pacemaker system or the implantation of mechanical assist device systems as well as the development of risk factor score systems to calculate the prognosis of patients with heart failure requires a new assessment of the indication for heart transplantation. The large number of heart transplanted patients and the results of randomized studies with new immunosuppressive drugs allow to calculate the risk, benefit and limitation of transplantation with relatively good reliability. These experiences and knowledge obtained and the German Transplantation Law, which passed the parliament in 1999, led to the establishment of a new heart allocation system. Additionally, by the central documentation of all transplantations in Germany, it becomes possible to compare the results of heart transplantations for better quality control.
A 26 year old man who presented with the first signs of right heart failure was found to have a large congenital aneurysm of the aortic sinus of Valsalva and of the left coronary sinus. These were combined with left heart anomalies in the form of a bicuspid aortic valve, a rare variant of a persistent left superior vena cava with blood flow from the left atrium through the brachiocephalic vein into the superior vena cava and a kink in the aortic arch. An aortic coarctation had been corrected with a patch 12 years earlier. Although the aneurysm was not perforated and there were no clinical signs of infarction, the aneurysm was resected prophylactically and the left coronary artery was reinserted through a bypass with a Gore-Tex conduit. The case is noteworthy because this diagnosis is very rare and its early treatment may prevent several complications. The clinical features, treatment, and outcome are discussed.
BACKGROUND AND OBJECTIVE: Left ventricular function is the most important predictor of survival in patients with coronary artery disease. It is also an important indicator for hospital mortality after operation for end-stage coronary artery disease. In our study we investigated, how preoperative ventricular dysfunction influences long term survival after coronary bypass surgery. PATIENTS AND METHODS: Between 4/1986 and 12/2000, 1751 patients (1440 men/311 women) with left ventricular ejection fraction (LVEF) 10-30% underwent coronary bypass grafting (CABG) at the Deutsches Herzzentrum Berlin. The age of the patients was calculated to an average of 59,2 years. The prime criterion for CABG was ischemia ("hibernating myocardium") diagnosed by myocardial scintigraphy, echocardiography and in some cases with magnetic resonance imaging and positron emission tomography. RESULTS: Operative mortality for the group was 7,1%. The actuarial survival rate was 87,6% after 2 years, 76,0% after 5, and 53,3% after 9. 455 had LVEF 10-20%, in these actuarial survival was 79,8% after 2 years, 63,0% after 5 and 45,7% after 9 years. CONCLUSION: We conclude that CABG can be used successfully to improve life expectancy of patients with end-stage coronary artery disease. CABG leads to acceptable prognosis for these high-risk patients when the myocardium is preoperatively identified as being viable.
Patients with a bicuspid aortic valve tend to develop local enlargement in the convexity of the ascending aorta. There is controversial discussion as to whether this is a dilatation caused by abnormal hemodynamic stress or an aneurysm due to a common developmental defect of the aortic valve and the aortic media. Systematic studies of aortic wall specimens from patients with different diameters of the ascending aorta have not been available until now. We investigated histologically (HE, E.v.G., alpha-Actin, Alcian blue/van Gieson) aortic wall tissue obtained from 107 patients (31 female, 76 male, mean age 60.9+/-12.8 years) with a bicuspid aortic valve. According to the preoperative measurement of the ascending aorta diameter, which was done by CT scan, angiography or echocardiography, the patients were divided into three groups [Group 1: ascending aorta diameter <3.8 cm; Group 2: diameter >/=3.8-4.9 cm and Group 3: diameter >/=5.0 cm]. We looked for histological signs of dilatation or more severe structural changes. All patients of group 1 showed normal findings in histological examination. In 23 of 43 patients in group 2 (65.1%), we found histological signs of dilatation. Histological signs of dilatation were present in all patients in group 3. We conclude that in patients with a bicuspid aortic valve histological signs of dilatation were more frequently found with increasing diameter of the ascending aorta. More severe histological changes, such as cystic media necrosis, were not present.
We report the case of a 45 year old man presenting to our emergency ward with acute onset of typical chest pain. The ECG showed ST-segment depression in the postero-lateral leads without elevation of any cardiac enzymes. The coronary angiogram showed a three-vessel disease with a subtotal, short stenosis of the right coronary artery and a severe ostial stenosis of the left main coronary artery. An operative revascularization with a venous graft to the right coronary artery and a angioplasty with an autologous vein patch of the left main coronary artery were performed. No peri- or postoperative complications occurred. Because of the importance of the left main coronary artery, the patient underwent an early post-operative coronary angiogram with intravascular ultrasound (IVUS) to confirm the patency of the patch angioplasty. We discuss the historical development, the indications and the main advantages of the patch angioplasty in comparison to conventional CABG procedures. The main issue of the presentation is the special value of IVUS in the pre- and postoperative assessment of the left main coronary artery. Within the last few years, IVUS has emerged from a pure research tool to the gold standard of coronary imaging. It is playing a more and more important role in the assessment of angiographically unclear lesions, mainly in the left main stem and its bifurcation. In addition, IVUS has a large influence in clinical decision making, e.g., reverral to CABG or PCI. It is also a powerful tool for optimizing the operative setting and provides the best possible postoperative control.