Partial versus Complete Sternotomy for Aortic Valve Replacement-Multicenter Study.

BACKGROUND: The benefits of minimally invasive techniques in cardiac surgery remain poorly defined. We evaluated the short- and mid-term outcomes after surgical aortic valve replacement through partial upper versus complete median sternotomy (MS) in a large, German multicenter cohort. METHODS: A total of 2,929 patients underwent isolated surgical aortic valve replacement via partial upper sternotomy (PUS, n = 1,764) or MS (n = 1,165) at nine participating heart centers between 2016 and 2020. After propensity-score matching, 1,990 patients were eligible for analysis. The primary end point was major adverse cardiac and cerebrovascular events (MACCE), a composite of death, myocardial infarction, and stroke at 30 days and in follow-up, up to 5 years. Secondary end points were acute kidney injury, length of hospital stay, transfusions, deep sternal wound infection, Dressler's syndrome, rehospitalization, and conversion to sternotomy. RESULTS: Unadjusted MACCE rates were significantly lower in the PUS group both at 30 days (p = 0.02) and in 5-year follow-up (p = 0.01). However, after propensity-score matching, differences between the groups were no more statistically significant: MACCE rates were 3.9% (PUS) versus 5.4% (MS, p = 0.14) at 30 days, and 9.9 versus 11.3% in 5-year follow-up (p = 0.36). In the minimally invasive group, length of intensive care unit (ICU) stay was shorter (p = 0.03), Dressler's syndrome occurred less frequently (p = 0.006), and the rate of rehospitalization was reduced significantly (p < 0.001). There were 3.8% conversions to full sternotomy. CONCLUSION: In a large, German multicenter cohort, MACCE rates were comparable in surgical aortic valve replacement through partial upper and complete sternotomies. Shorter ICU stay and lower rates of Dressler's syndrome and rehospitalization were in favor of the partial sternotomy group.

Telemedicine-guided, very low-dose international normalized ratio self-control in patients with mechanical heart valve implants.

AIM: To study in patients performing international normalized ratio (INR) self-control the efficacy and safety of an INR target range of 1.6-2.1 for aortic valve replacement (AVR) and 2.0-2.5 for mitral valve replacement (MVR) or double valve replacement (DVR). METHODS AND RESULTS: In total, 1304 patients undergoing AVR, 189 undergoing MVR and 78 undergoing DVR were randomly assigned to low-dose INR self-control (LOW group) (INR target range, AVR: 1.8-2.8; MVR/DVR: 2.5-3.5) or very low-dose INR self-control once a week (VLO group) and twice a week (VLT group) (INR target range, AVR: 1.6-2.1; MVR/DVR: 2.0-2.5), with electronically guided transfer of INR values. We compared grade III complications (major bleeding and thrombotic events; primary end-points) and overall mortality (secondary end-point) across the three treatment groups. FINDINGS: Two-year freedom from bleedings in the LOW, VLO, and VLT groups was 96.3, 98.6, and 99.1%, respectively (P = 0.008). The corresponding values for thrombotic events were 99.0, 99.8, and 98.9%, respectively (P = 0.258). The risk-adjusted composite of grade III complications was in the per-protocol population (reference: LOW-dose group) as follows: hazard ratio = 0.307 (95% CI: 0.102-0.926; P = 0.036) for the VLO group and = 0.241 (95% CI: 0.070-0.836; P = 0.025) for the VLT group. The corresponding values of 2-year mortality were = 1.685 (95% CI: 0.473-5.996; P = 0.421) for the VLO group and = 4.70 (95% CI: 1.62-13.60; P = 0.004) for the VLT group. CONCLUSION: Telemedicine-guided very low-dose INR self-control is comparable with low-dose INR in thrombotic risk, and is superior in bleeding risk. Weekly testing is sufficient. Given the small number of MVR and DVR patients, results are only valid for AVR patients.

Clinical impact of a new bioprosthetic aortic valve: the St. Jude Medical Trifecta™.

BACKGROUND: The St. Jude Medical (SJM) Trifecta™ aortic valve was designed to face common issues such as high transvalvular pressure gradients and low effective orifice areas (EOAs), which lead to prosthesis-patient mismatch after implanting small valve sizes. To reduce the obstruction of the left ventricular outflow tract, the Trifecta™ was designed as a stented valve for supraannular placement. The aim of this study was to evaluate the early hemodynamic performance of this new valve. METHODS: Between September 2010 and February 2013, 380 patients underwent an aortic valve replacement (AVR) using the SJM Trifecta™. Patients were subsequently followed up for two years and data records were analyzed retrospectively. Mean patient age was 73 years (range 33-93 years), 58% were male. The average mean preoperative pressure gradient was 45mmHg, with an EOA of 0,73cm2. The majority of patients (62%) were in NYHA class III. Indication for AVR was valve stenosis or insufficiency in 95%, presence of endocarditis caused the AVR in 5%. RESULTS: The 30-day-mortality was 4% (n=16; mean log EuroSCORE 20.9%), including two intraoperative non-valve-related cardiac deaths (0.52%) and one valve-related death due to lethal aortotomy bleedings (0.26%). 25 patients died during the follow-up period, 9 of them in a valve-related manner. At discharge, no valve thromboses or prosthesis failures could be identified. The average EOA and mean pressure gradient at discharge was 1.36cm2 and 11mmHg for 19mm valves and 2.1cm2 and 7mmHg for 25mm valves. CONCLUSIONS: The new SJM Trifecta™ demonstrates excellent early hemodynamics over all valve sizes. In particular, large EOAs and low gradients in small valves attest a satisfying outcome after implantation. Further data is needed to investigate the stableness of these results over long-term follow up.

Preoperative hemostasis and its association with bleeding and blood component transfusion requirements in cardiopulmonary bypass surgery.

BACKGROUND: Variables of hemostasis before surgery might indicate an elevated risk of bleeding. We determined hemostasis tests and standardized bleeding history and their association with bleeding and transfusion requirements in cardiopulmonary bypass (CPB) surgery. STUDY DESIGN AND METHODS: In a prospective trial, variables from 104 patients were associated with postsurgical bleeding and with red blood cells (RBCs) and platelet concentrate (PC) transfusions. Variables included standardized bleeding history, prothrombin time (PT), fibrinogen, fibrin monomers, Factor VIII, von Willebrand factor (VWF), multiple electrode aggregation (MEA), and the day of aspirin or thienopyridine withdrawal before operation. RESULTS: Multiple linear regression revealed bleeding history score, ADP-induced MEA, CPB time, and hemoglobin (Hb) independently associated with postoperative bleeding and bleeding history, arachidonic acid (AA)-induced MEA, CPB time, and PT associated with RBC transfusions. The logistic regression model for the outcome of bleeding within 24 hours after operation indicated ADP-induced MEA, the day of aspirin withdrawal before operation, and CPB time as predictors. AA-induced MEA, CPB time, Hb, and PT were predictors of RBCs transfusion. ADP-induced MEA, the day of aspirin withdrawal, PT, and VWF were associated with PC transfusion. CONCLUSIONS: A standardized bleeding history may help to identify patients undergoing CPB surgery whose risk of bleeding is elevated. ADP-induced MEA appears to predict postoperative bleeding and PC transfusion requirements, while AA-induced MEA and preoperative Hb indicate the need for RBCs. The time of aspirin withdrawal before surgery influences perioperative blood loss and PC transfusion.

Transcatheter mitral valve implantation versus conventional redo surgery for degenerated mitral valve prostheses and rings in a multicenter registry.

OBJECTIVES: Degeneration of mitral prostheses/rings may be treated by redo surgery, and, recently, by transcatheter valve-in-valve/ring implantation. This multicenter registry presents results of transcatheter valve-in-valve and repeat surgery for prostheses/rings degeneration. METHODS: Data provided by 10 German heart centers underwent propensity score-matched retrospective analysis. The primary endpoint was 30-day/midterm mortality. Perioperative outcome was assessed according to the Mitral Valve Academic Research Consortium criteria. Further, the influence of moderate or greater tricuspid regurgitation (TR) on 30-day/midterm mortality was analyzed. RESULTS: Between 2014 and 2019, 273 patients (79 transcatheter mitral valve-in-valve [TM-ViV] and 194 redo mitral valve replacement [Re-MVR]) underwent repeat procedure for mitral prosthesis/ring degeneration. Propensity score matching distinguished 79 patient pairs. European System for Cardiac Operative Risk Evaluation (EuroSCORE) II-predicted risk was 15.7 ± 13.7% in the TM-ViV group and 15.0% ± 12.7% in the Re-MVR group (P = .5336). TM-ViV patients were older (74.73 vs 72.2 years; P = .0030) and had higher incidence of atrial fibrillation (54 vs 40 patients; P = .0233). Severe TR incidence was similar (17.95% in TM-ViV vs 14.10%; P = .1741). Sixty-eight TM-ViV patients previously underwent mitral valve replacement, whereas 41 Re-MVR patients underwent valve repair (P < .0001). Stenosis was the leading degeneration mechanism in 42 TM-ViV versus 22 Re-MVR patients (P < .0005). The 30-day/midterm mortality did not differ between groups. Moderate or greater TR was a predictor of total (odds ratio [OR], 4.36; P = .0011), 30-day (OR, 3.76; P = .0180), and midterm mortality (OR, 4.30; P = .0378), irrespective of group. CONCLUSIONS: In both groups, observed mortality was less than predicted. Redo surgery enabled treatment of concomitant conditions, such as atrial fibrillation or TR. TR was shown to be a predictor of total, 30-day, and midterm mortality in both groups.

Endocarditis at a large community hospital with on-site cardiac surgery.

OBJECTIVE: Infective endocarditis (IE) is still a serious disease. The currently published EURO-ENDO registry showed a rate of surgery of 51.2% and a lower mortality in operated IE patients. We hypothesized differences between our data and the registry. METHODS: Retrospective single centre registry on the hospital course of patients with IE. RESULTS: In four years, 171 IE patients were treated at our hospital. Mean age of patients was 66.5 ± 13.8 years and 62.6% of patients were transferred from other hospitals. There were 85 (49.7%) patients with native valve IE (NVE), 53 (31%) with prosthetic valve IE (PVE) and 33 (19.3%) with either intra-cardiac device related IE (n = 29) or IE associated with central access lines (n = 4) (DRE). A total of 81.3% (n = 139) of patients were sent to cardiac surgery. Using a logistic regression model to analyse predictors of conservative instead of surgical therapy the only independent variables were: presence of large vegetation or abscesses (OR: 0.36, 95%CI 0.15-0.83; p = 0.016) and age (for each ten years) (OR: 1.61, 95%CI 1.11-2.32, p = 0.01). Hospital mortality was 21.6% (n = 37/171), with no difference (p = 0.97) between those who were operated (21.6%, n = 30/139) and those treated conservatively (21.9%, n = 7/32). Comparing those treated conservatively without an indication for surgery with those with an indication, mortality was 9.5% versus 45.5%, p = 0.02. CONCLUSIONS: In this registry from a hospital with on-site cardiac surgery more than half of patients were referred. The rate of patients treated surgically was 81.3%. Hospital mortality was 21.6%, with no difference between operated and conservatively treated patients.

Negative pretransplant serostatus for Toxoplasma gondii is associated with impaired survival after heart transplantation.

Chronic Toxoplasma gondii infection is known to trigger potentially adverse immunoregulatory changes, but limited data exist on long-term implications for heart transplant (HTX) recipients. We evaluated the risk of all cause mortality regarding T. gondii serostatus prior to HTX. Pre-HTX T. gondii serostatus was obtained in 344 recipients and 294 donors. Mean age was 52.1 +/- 10.2 years and mean follow-up time after HTX was 5.7 (+/-5.5, median 3.5) years. All seronegative patients received prophylaxis with pyrimethamine/sulfomethoxazole or cotrimoxazol for 6 months after transplantation. Multivariate survival analysis adjusted for diabetes mellitus, pre-HTX renal function, recipient age, type of primary immunosuppression (i.e. HTX before 2001), cytomegalovirus (CMV) high-risk status, ischemic time, and number of treated rejection episodes was performed. Overall, 190 recipients (55.2% of total) were seronegative and 154 (44.8% of total) were seropositive for T. gondii prior to HTX. One hundred and fifty-two recipients died during follow-up (44.2% of total). Negative recipient Toxoplasma serostatus was associated with a significantly higher risk of all-cause mortality (P = 0.0213). Recipient T. gondii serostatus did not influence the number of cellular or humoral rejection episodes. Analyses of specific causes of death showed a trend toward a higher number of infection-related deaths in the seronegative subgroup (P = 0.13). No statistically significant effects of T. gondii donor/recipient seropairing, or seroconversion were observed. Negative preoperative serostatus for T. gondii in HTX recipients appears to be an independent risk factor associated with increased all-cause mortality. The cause of impaired survival in Toxoplasma seronegative recipients is currently unclear; possible explanations include an alteration of immune-reactivity/-regulation or adverse effects of prophylactic medication.

Prophylactic implantation of cardioverter-defibrillator in patients with severe cardiac amyloidosis and high risk for sudden cardiac death.

BACKGROUND: Cardiac light-chain amyloidosis carries a high risk for death predominantly from progressive cardiomyopathy or sudden death (SCD). Independent risk factors for SCD are syncope and complex nonsustained ventricular arrhythmias. OBJECTIVE: The purpose of this study was to test whether prophylactic placement of an implantable cardioverter-defibrillator (ICD) reduces SCD in patients with cardiac amyloidosis. METHODS: Nineteen patients with histologically proven cardiac amyloidosis and a history of syncope and/or ventricular extra beats (Lown grade IVa or higher) received an ICD. RESULTS: During a mean follow-up of 811 +/- 151 days, two patients with sustained ventricular tachyarrhythmias were successfully treated by the ICD. Two patients underwent heart transplantation, and seven patients died due to electromechanical dissociation (n = 6) or glioblastoma (n = 1). Nonsurvivors more often showed progression of left ventricular wall thickness, low-voltage pattern, ventricular arrhythmias (Lown grade IVa or higher), and higher N-terminal pro-brain natriuretic peptide levels than did survivors. Bradycardias requiring ventricular pacing (VVI 40/min <1%, DDD 60/min 6% +/- 1%) occurred only rarely. CONCLUSION: Patients with cardiac amyloidosis predominantly die as a result of electromechanical dissociation and other diagnoses not amenable to ICD therapy. Selected patients with cardiac amyloidosis may benefit from ICD placement. Better predictors of arrhythmia-associated SCD and randomized trials are required to elucidate the impact of ICD placement in high-risk patients with cardiac amyloidosis.

Treatment options for severe cardiac amyloidosis: heart transplantation combined with chemotherapy and stem cell transplantation for patients with AL-amyloidosis and heart and liver transplantation for patients with ATTR-amyloidosis.

OBJECTIVE: Cardiac amyloidosis (CA) is associated with a poor prognosis and a survival rate of less than 30% 2 years after clinical manifestation. Considered as a semi-malignant disease, CA is often a contraindication for HTx; however, depending on the type of CA, there are excellent treatment regimes that can be combined with HTx. In AL-amyloidosis, chemotherapy and stem cell transplantation are necessary and in TTR-amyloidosis, where the liver is the source of the pathologic protein, liver transplantation is recommended after HTx. METHODS AND RESULTS: More than 60 patients with AL-amyloidosis and more than 25 patients with ATTR-amyloidosis have been investigated at our centre. Eighteen patients showed signs of end-stage heart failure. Four patients died within 1 month after listing for HTx. Seven patients with AL (mean age 41.8 years) and five patients with ATTR-amyloidosis (mean age 42.6 years) were successfully transplanted with an actual survival rate of 91.6%. One patient died 8 months after HTx due to infection. Five AL patients received chemotherapy and SCT and one ATTR patient was liver transplanted. Three AL patients showed complete remission of amyloidosis. CONCLUSIONS: Cardiac amyloidosis is a potentially curative disease after HTx when combined with either chemotherapy and SCT or LiverTx depending on the type of the amyloidosis. Due to the natural course of the disease, urgent HTx after cardiac manifestation is mandatory. With this approach, excellent survival rates and even remission of the underlying disease is possible.

Inducible NO synthase expression in endomyocardial biopsies after heart transplantation in relation to the postoperative course.

OBJECTIVE: Ischemia and reperfusion during heart transplantation cause damage to cardiomyocytes and endothelial cells and may initiate later acute rejection. Free oxygen radicals generated by iNOS are widely accepted to be responsible for ischemic injury. Increased iNOS expression on cardiac tissue may represent a more intensive tissue injury during ischemia and reperfusion in heart transplantation. The aim of this study was, therefore, to test the hypothesis that increased iNOS expression in early postoperative endomyocardial biopsies correlates with rejection or infection episodes in the later postoperative course. PATIENTS AND METHODS: Right ventricular endomyocardial biopsies were obtained from heart transplantation recipients at transplantation and during the first 2 weeks postoperatively. The recipients were divided into three groups depending on the postoperative course during the first year after transplantation: patients in group 1 had an uncomplicated postoperative course, patients in group 2 developed significant signs of postoperative infection, while patients in group 3 presented with acute rejection (< or =grade 2R ISHLT). The expression was analyzed in a semi-quantitative score. RESULTS: iNOS expression was found in cardiomyocytes, endothelial cells, infiltrating cells, and vascular smooth muscle cells. At the time of heart transplantation, the expression was significantly increased in the rejection group compared to the other groups. This increase was even more pronounced in week 2. CONCLUSIONS: The present study shows that an increased iNOS expression at the time of heart transplantation could precede an acute rejection in the later postoperative course. Thus, measurements of iNOS expression may be of predictive value for an increased rejection risk and therefore offer the possibility of earlier therapeutic intervention.

Biomarkers after heart transplantation: nongenomic.

Patient monitoring following heart transplantation aims to detect complications (eg, acute graft rejection, vasculopathy, infection) early and contributes to risk prognostication. Numerous biomarkers of different biologic pathways have been evaluated as ancillary diagnostic and prognostic tools to reduce the need for invasive and expensive technical investigations. With the possible exception of cardiac troponins and N-type natriuretic peptides, no biomarkers have become established firmly in posttransplant patient surveillance. This article aims to show that the identification of a single biomarker that meets all needs (noninvasive diagnosis of rejection, prediction of transplant vasculopathy, survival prognostication) is unlikely. Rather, multiple marker strategies, including gene-based tests, are likely to enhance future monitoring quality and enable individualized risk-adapted patient management.

A clinical study of annular geometry and dynamics in patients with ischemic mitral regurgitation: new insights into asymmetrical ring annuloplasty.

OBJECTIVE: Recent studies in animals showed that regional annulus distortion is a major determinant of ischemic mitral regurgitation (IMR) and accordingly suggested new surgical approaches with asymmetrical annuloplasty rings. As accurate measurement of annulus in patients is still a challenge, we performed this study to analyze the changes in three-dimensional annular geometry in patients with IMR compared to primary valvular lesions. METHODS: We studied 110 patients divided into three groups: (1) 30 with coronary artery disease without IMR, (2) 38 with chronic IMR, and (3) 42 with MR due to primary valvular lesions. Longitudinal and septal-lateral annulus diameters; global diastolic and systolic annular area and its percentual shortening, diastolic and systolic areas of six regions corresponding to the segmental Carpentier classification were measured by 3D-echocardiography. The degree of MR was assessed by three-dimensional color Doppler. Global and regional left ventricular geometry were assessed by sphericity index and by measuring anterior and posterior tethering of papillary muscles. RESULTS: Patients with significant IMR (group 2) showed larger longitudinal (52.7+/-3.9 mm vs 41.8+/-2.9 mm; p<0.01) and antero-lateral (31.8+/-3.5mm vs 26.7+/-2.8mm; p<0.01) annular diameters than the patients with MR due to primary valvular lesions (group 3). Diastolic (997.8+/-64.9 mm(2) vs 700.7+/-46.8mm(2); p<0.01) and systolic (894.9+/-57.3mm(2) vs 547.3+/-35.0mm(2); p<0.01) annular areas were larger in group 2 than in group 3. Annular area change was significantly lower in the group with ischemic mitral regurgitation than in the group with primary valvular lesions (10.3+/-1.1% vs 21.9+/-1.6%; p<0.01). Regional annular areas of the six sectors were homogeneously larger in group 2 than in group 3. The sector P3 did not show larger area than the other ones. The degree of MR, as assessed by the volumes of regurgitant jets, was higher in the group with primary valvular lesions than in the patients with IMR (32.6+/-13.4 cm(3) vs 23.1+/-11.1cm(3); p<0.01). CONCLUSIONS: This study showed that annular enlargement in patients with IMR affects the different annular regions to the same extent. An ideal surgical repair of IMR should be individually tailored after quantitative assessment measurement of geometry and function of each single component of the mitral valve complex.

Morphometric changes of the right ventricle in the first two weeks after clinical heart transplantation: analysis of myocardial biopsies from patients with complicated versus uncomplicated course.

OBJECTIVE: The early phase following heart transplantation (HTx) is characterized by the development of right ventricular myocardial fibrosis (MF) and cardiomyocyte hypertrophy (CH). The question is if there are differences in development of MF and CH between patients with complicated versus patients with uncomplicated postoperative course. METHODS: Endomyocardial biopsies were taken from 58 donor hearts before implantation and one and two weeks after HTx. According to the clinical course in the first year after HTx and the rejection grading (ISHLT), four groups were classified: (a) uneventful course, (b) transplant failure, (c) infections, and (d) rejection episodes > or = 1R. The volume densities of various tissue components and cardiomyocyte diameters were measured by stereological and morphometrical methods. RESULTS: From implantation to the first two weeks, most groups showed a significant increase of endomysial and perimysial connective tissues. There was a significant CH recognizable, especially in the rejection group. However, nucleus surface, a hypertrophy parameter, showed no significant change during follow-up. There were no statistically significant differences in volume densities of interstitial space, capillaries, nuclei and cardiomyocytes between the collectives and points in time. Sarcomere length as marker of contraction status of cardiomyocytes remained at the same level and showed no significant differences. Demographic data showed no significant differences and will be presented. CONCLUSIONS: Patients with complicated and uncomplicated courses show different degrees of histopathological changes after HTx. The extent of hypertrophy differs especially between the collectives. Measurement of endomysial connective tissue points to later postoperative course in the recipient. These findings may reflect a pattern of remodeling specific to the transplanted heart.

Risk stratification in cardiac amyloidosis: novel approaches.

Amyloidosis is a term for diseases with extracellular deposition of insoluble beta-fibrillar proteins in different organs. The heart is primarily involved in more than half of patients with immunoglobulin light-chain amyloidosis or hereditary amyloidosis and associated with poor prognosis. Different traditional diagnostic tools that have been described for risk stratification lack of sufficient sensitivity and specificity for patient survival. Until November 2004 in 50 consecutive patients with light chain amyloidosis and 15 patients with hereditary amyloidosis electrocardiography, echocardiography, Holter monitoring, cardiopulmonary exercise test, lung function testing, tilt-test, and laboratory investigations have been performed at our department. Cardiac amyloidosis was found in 32 patients. Interventricular septum (14.3+/-0.5 mm vs. 12.3+/-0.7 mm, P<0.05), plasma NT-proBNP (7154+/-2122 ng/l vs. 380+/-113 ng/l; P<0.01), cardiac Troponin T (0.105+/-0.030 vs. 0.019+/-0.010 microg/l; P<0.05) were increased in patients with cardiac amyloidosis as compared to patients light chain amyloidosis but no cardiac involvement. Maximal inspiratory (Pimax) and expiratory (Pemax) mouth pressure were decreased with CA compared to controls. Correlation of NT-proBNP and interventricular septum thickness (r=0.53, P=0.029) as well as and Pimax (r=0.72, P<0.01) or Pemax (r=0.69; P<0.01) was noticed. A correlation of grade of arrhythmias in Holter monitoring and syncopes was not observed. Cardiac involvement of amyloid disease carries a poor prognosis and is not well characterized by classic heart failure determinants. Heart transplantation based on novel risk markers including NT-proBNP might be a suitable therapeutic approach for patients with manifest cardiac amyloidosis, but will require alternative patient selection and listing criteria.

Effectivity of a T-cell-adapted induction therapy with anti-thymocyte globulin (Sangstat).

BACKGROUND: Cytolytic induction therapy with anti-thymocyte globulin (ATG) should induce effective immunosuppression, with a low rate of rejection in the initial phase after heart transplantation. Induction therapy with ATG allows post-operative renal recovery without the negative effects of highly nephrotoxic cyclosporine levels. An increased rate of infection is a common problem, however, and has been associated with "over-immunosuppression" early after transplantation. Therefore, we investigated whether reduced T-cell-adapted ATG induction therapy could be performed without increasing the risk of graft loss by rejection and whether reductions in infection rates and costs are possible. METHODS: Between March 1999 and December 2002, T-cell-adapted ATG induction therapy with ATG (Sangstat) (1.5 mg/kg) was given to 62 heart transplant recipients (study group) starting on post-operative Days 1 to 6. T-lymphocyte sub-populations were screened daily using flow cytometry. If total lymphocytes were <100/microl (reference 1,300 to 2,300/microl), T-helper lymphocytes (CD4+) <50/microl (reference >500/microl) and T-suppressor cells (CD8+) <50/microl (reference >300/microl), then no ATG was given. Further immunosuppression was continued with triple therapy consisting of methylprednisolone, azathioprine and cyclosporine. An historic group of heart transplant recipients given a full-dose ATG regimen for 8 days served as controls. These recipients were treated with ATG (Merieux 1.5 mg/kg) until reaching monoclonal cyclosporine levels of >300 mg/dl. Additional immunosuppressive treatment did not differ. Patients in both groups received systemic antibiotics (Imipenem) peri-operatively. Results of routine endomyocardial biopsies and rates of infections were examined. RESULTS: Study group patients were older (52 +/- 10 vs 49 +/- 14 years). In the study group, mean cumulative ATG dose was reduced significantly to 596 +/- 220 mg (p < 0.05) for 3.9 +/- 1.6 days compared with 1,159 +/- 376 mg for 6.9 +/- 1.1 days in the control group. The rate of cytomegalovirus (CMV) seroconversion was 23% in the study group compared with 13% in the control group. Rate of deep sternal infections was lower in the study group (1.6% vs 3.2%). The mean rejection rate in the first 3 months was 0.4 +/- 0.7 for the study patients (185 biopsies) vs 1.1 +/- 1.7 for controls (237 biopsies). All biopsies with ISHLT Grade >2 were treated successfully with 1,000 mg of methylprednisolone intravenously for 3 days. Both groups showed a similar 1-year survival rate (study 88%, control 89%). CONCLUSIONS: T-cell-adapted ATG induction therapy can be a helpful tool for individualized immunosuppression. It is not associated with an increased rate of rejection. Lower doses of immunosuppression help to minimize the rates of infection. In addition, cytolytic induction therapy combined with reduced ATG results in significant cost reduction.

Cystic thymoma.

Thymic cysts are rare lesions located along the anatomical course of the third pharyngeal pouch. While most of the cases represent congenital cysts, they may also be related to neoplasms. We report a case of a micronodular thymoma with lymphoid stroma, which was completely built of small cysts, discuss the pathologic features of this tumor type and review the etiology and other aspects of thymic cysts.

Influence of different implantation techniques on AV valve competence after orthotopic heart transplantation.

OBJECTIVE: About a decade after the introduction of the bicaval and pulmaonary venous heart transplantation technique a reduction of tricuspid and mitral valve incompetence compared to the standard technique by Lower and Shumway is still discussed controversially. We used this technique regularly since the year 1993 and report about our 10 years experience. METHODS: A total of 297 patients were transplanted at our institution between 1989 and 2003, 158 with the standard and 139 in the total orthotopic technique (TOHT). Ninety-four of the standard and 72 of the TOHT group were followed up as outpatients and were examined with right-heart catheterisation and trans-thoracic echocardiography. RESULTS: Patients in both groups were similar in demographic data. Right heart catheterisation showed no statistical significant differences between the two groups. The left atrium was significantly enlarged in the standard group. The TOHT group showed a significant reduction of tricuspid regurgitation in 5-year follow up echocardiography. CONCLUSION: This study showed excellent long-term survival rates for both groups. The significant reduction of left atrial size and atrio-ventricular valve regurgitation in the TOHT group might have important impact on the long-term preservation of cardiac function. Total orthotopic heart transplantation with bicaval and pulmonary venous anastomosis should be preferred for heart transplantation.

Fibroelastoma Recurrence in Left Ventricle: Rarity of Primary Cardiac Tumor.

Cardiac papillary fibroelastoma (CPF) is a primary cardiac neoplasm usually detected by echocardiography. Left ventricular fibroelastomas are extremely rare. The incidence of CPF is between 0.0017 and 0.33% during autopsy studies. We report a 70-year-old man who had papillary fibroelastoma discovered and resected in 2005 that recurred in 2013. The tumor grew rapidly from 2013 to 2014. A bioprosthetic mitral valve was placed in 2014. Due to the location and nature of the recurrent tumor, mitral valve replacement was the treatment of choice to prevent a third recurrence of the fibroelastoma. The patient was discharged from the hospital on postoperative day 9.

Allograft rejection of ISHLT grade >/=3A occurring late after heart transplantation--a distinct entity?

BACKGROUND: The significance of International Society of Heart and Lung Transplantation (ISHLT) grade >/=3A rejection detected by routine endomyocardial biopsies beyond 2 years post-transplant remains uncertain. METHODS: We performed a retrospective analysis of our single-institution database consisting of 4,041 biopsies (188 patients) from 1986 to 2001. Incidence, clinical correlates and outcome of ISHLT grade >/=3A rejection beyond 2 years post-transplant were analyzed. RESULTS: A total of 307 ISHLT grade >/=3A rejection episodes was diagnosed up to 10 years after transplantation, 69 of which occurred later than 2 years post-transplant in 33 of 139 patients ("late rejection") at therapeutic levels of immunosuppression. Late rejection was only marginally correlated with the incidence of moderate rejection within the first 2 post-transplant years (p = 0.09). The incidence of moderate rejection per patient-year decreased from 1.05 in Year 1 over 0.11 in Year 5 to 0.04 in Year 10. The technical failure rate of biopsies remained low throughout the post-transplant period (range 0.7% to 2.4%). Spontaneous resolution of ISHLT grade >/=3A rejection beyond 2 years post-transplant occurred in all 17 patients in whom specific anti-rejection therapy had been electively withheld. Mortality beyond 2 years post-transplant was lower (p = 0.033) in the "late rejecting" group (n = 33) than in the control group (n = 106). CONCLUSIONS: Endomyocardial biopsy continues to detect episodes of moderate rejection even very late after heart transplantation, without a close correlation with the rejection frequency in the early post-transplant period. Even without specific treatment, late rejection carries a benign clinical prognosis and may represent a separate biologic entity. Potential long-term effects-for instance, on the pathogenesis of transplant vasculopathy-need further elucidation.