Munich lung transplant group: waiting list during the first 9 months of the lung allocation score era.

OBJECTIVE AND METHODS: The Eurotransplant Foundation introduced the lung allocation score (LAS) in Germany on December 10, 2011. We analyzed characteristics of the Munich Lung Transplant Group (MLTG) waiting list during the first 9 months after the introduction of the LAS. RESULTS: A mean number of 39 ± 1 patients were constantly listed for lung transplantation and 60 transplants were performed by the MLTG during the observation period. While the majority (42 ± 0%) of patients waiting for transplant comprised chronic obstructive pulmonary disease (COPD)/emphysema patients, only 26% of transplanted patients suffered from COPD/emphysema. Instead, the majority (42%) of transplanted patients suffered from interstitial lung disease. Waiting times did not markedly change in the LAS era. Notably, patients with interstitial lung disease had shorter waiting times when compared with patients suffering from COPD/emphysema and cystic fibrosis, both on the waiting list and at the time of transplant. CONCLUSION: The MLTG lung transplant waiting list has not markedly changed during the first 9 months after the introduction of the LAS. Our data indicate that the LAS accommodates disease-specific patient statuses well. Although patients with interstitial lung disease are preferably transplanted, the LAS system provides a very reasonable basis to also list and transplant COPD/emphysema patients.

Gender does matter: gender-specific outcome analysis of 67,855 heart transplants.

BACKGROUND: Gender differences between donor and recipient might have an impact on the outcome after heart transplantation (HT). Data of more than 67,000 patients registered at the International Society of Heart Lung Transplantation (ISHLT) were reviewed focusing on the influence of gender differences on short- and long-term outcome after HT. METHODS: We performed a retrospective analysis of 67,855 cardiac allograft recipients. They received orthotopic HT between January 1, 1980 and June 30, 2009. In contrast to other studies the data for gender differences (donor gender and recipient gender) were calculated with respect to actuarial and conditional survival (without 30-day mortality). RESULTS: One-year survival was highest in male recipients of male donor hearts (mR/mD: 83.74%). The lowest 1-year outcome showed male recipients of female donor organs (mR/fD: 78.95%). Best 5-year survival rates were shown by male recipients with male donor organs (70.75%, p < 0.0001). These differences disappeared in survival conditional to 1 year, indicating that gender predominantly influences short-term outcome. CONCLUSIONS: The combination male recipient/female donor carries a higher risk for early mortality, whereas female recipients/male donor reveals favorable short-term results. Gender-matched HT would be ideal, but not suitable in practice because of the shortage of organs.

The Munich-LTX-Score: predictor for survival after lung transplantation.

BACKGROUND: The purpose of this study was to create a prognostic score calculated one yr after LTX based on post-transplant factors inclusive of donor and recipient characteristics that could be used to predict long-term survival in patients after lung transplantation (LTX). METHODS: Uni- and multivariate analysis in 206 consecutive LTX patients identified independent risk factors for post-transplant mortality and onset of bronchiolitis obliterans syndrome. Munich-LTX-Score is devised by summing up each identified risk factor. RESULTS: Multivariate analyses revealed acute rejection, lymphocytic bronchiolitis, donor age ≥ 55 yr, and HLA-A ≥ 2-/DR ≥ 2 mismatch and single LTX to be independent negative predictors for long-term survival (p < 0.05). Munich-LTX-Score identified three discrete groups: low-, moderate-, and high risk. The actuarial five-yr survival after score calculation one yr after LTX of the entire cohort was 58%, compared with 91% in low-, 54% in moderate-, and 0% in the high-risk group (p < 0.001). CONCLUSION: Within our cohort of patients calculation of the Munich-LTX-Score, consisting of donor-, recipient-, and post-transplant characteristics, one yr after LTX allowed to predict long-term survival of lung transplant recipients. After prospective validation, this score could identify patients who may benefit from intensified surveillance after LTX.

Long-term outcomes after 1000 heart transplantations in six different eras of innovation in a single center.

The objective of this study was to evaluate long-term outcomes of cardiac transplantation (HTx) in different eras of innovation at a single center during a period of 27 years. We performed a retrospective analysis of 960 cardiac allograft recipients (40 re-HTx) between 1981 and 2008. The results of six different eras based on milestones in HTx were analysed: Era 1: the early years (n = 222,1981-1992); era 2: introduction of inhalative nitric oxide, prostanoids, University of Wisconsin solution (UW) replacing Bretschneider's solution (HTK,n = 118, 1992-1994); era 3: statins (n = 102, 1994-1995); era 4: tacrolimus(n = 115, 1995-1996); era 5: mycophenolate mofetil (MMF, n = 143, 1997-2000) and era 6: sirolimus (n = 300, 2000-2008). Outcome variables weresurvival, freedom from cardiac allograft vasculopathy (CAV) and from acute rejection episodes (AREs). Differences in survival was found comparing era 1 and era 2 with era 4 and era 6 (P < 0.001). Organ preservation through UW demonstrated a significantly better survival as compared with HTK(P < 0.001). Less AREs occurred in patients receiving tacrolimus-sirolimus ortacrolimus-MMF (P < 0.001). Patients receiving tacrolimus-MMF showed less CAV than when treated with cyclosporine-MMF (P < 0.005). There were more ventricular assist device implantations and more re-HTx in era 6 (P < 0.0001)than when compared with other eras. Although the causes for improvement in survival over time are multifactorial, we believe that changes in immunosuppressive therapy have had a major impact on survival.

Calcineurin inhibitor withdrawal and conversion to mycophenolate mofetil and steroids in cardiac transplant recipients with chronic renal failure: a word of caution.

BACKGROUND: Chronic renal failure (CRF) is a common complication of calcineurin inhibitor (CNI)-based immunosuppression following cardiac transplantation (HTx). The aim of this prospective study was to evaluate the impact of an immunosuppressive conversion from CNIs to mycophenolate mofetil (MMF) and steroids in cardiac transplant recipients with CRF on renal and cardiac graft function. METHODS: Since 1999, 12 HTx recipients (10 men; 58 +/- 3.6 yr of age; 8.7 +/- 4.2 yr after HTx) with CNI-based immunosuppression and a calculated creatinine clearance (CreaCl) <50 mL/min were included. Most patients (10/12) were on cyclosporine and two patients were on tacrolimus prior inclusion. MMF was started with 0.5 g/d and adjusted according to the target trough levels (2-4 ng/mL). Prednisone dosage was 0.4 mg/kg. Subsequently, CNIs were completely withdrawn. Acute rejection episodes were excluded one and three months after conversion by endomyocardial biopsy and by echocardiography every three months thereafter. RESULTS: After a mean follow-up of 20 +/- 16 months, CreaCl improved significantly: pre-conversion vs. post-conversion: 32.8 +/- 12.2 mg/dL vs. 42.8 +/- 21.14 mg/dL, p = 0.03. However, four acute rejection episodes occurred and patients were reconverted to CNIs. Additionally, six patients had a new onset of graft vessel disease (GVD) one yr after conversion. As a result of these adverse events, the study was stopped after inclusion of only 12 of the scheduled 30 patients. CONCLUSIONS: Conversion to MMF and steroids after HTx improves renal function, but increases the risk for recurrent rejection and GVD. Therefore, MMF and steroids should only be considered in patients with a markedly low risk for rejection.

Mediastinal pheochromocytoma with single coronary blood supply: a case report.

Primary pheochromocytomas located outside the adrenal glands account for only 10% of all pheochromocytomas. Mediastinal pheochromocytomas are even rarer and usually represent a therapeutic challenge as they often infiltrate adjacent structures. We report the case of a large primary mediastinal pheochromocytoma in a 65-year-old patient presenting with a sudden angina-like chest pain and dyspnea. Thoracic multislice computed tomography showed an 8 x 5 x 6-cm retrocardiac mass causing compression of both atria and infiltrating the left superior pulmonary vein. The tumor was highly vascularized and presented a blood supply derived from the circumflex artery. The mass was successfully removed by open heart surgery, and the patient was discharged 10 days postoperatively.

Impact of donor serum sodium levels on outcome after heart transplantation.

We investigated the impact of elevated donor serum sodium levels on outcome after heart transplantation in 336 consecutive heart transplantations. Mean donor serum sodium was 148.2+/-10.2 mmol/liter (range 116 to 180 mmol/liter). Recipients were divided into 4 groups with serum sodium levels of 141, 147 and 155 mmol/liter, resulting in sodium levels of: 133+/-6.1 mmol/liter for Quartile A; 144+/-4.2 mmol/liter for Quartile B; 151+/-4.3 mmol/liter for Quartile C; and 162+/-6.6 mmol/liter for Quartile D, respectively (mean+/- standard deviation). Mean occurrence of primary graft failure (PGF) was 3.6% with the following quartile breakdown: A, 3.6%; B, 4.8%; C, 3.6%; and D, 2.4% (p=non-significant [NS]). Mean 5-year survival was 81.32% with: A, 83.51%; B, 76.03%; C, 80.47%; and D, 85.25% (p=NS). Coronary allograft vasculopathy (CAV) occurred in 19% of patients with a quartile breakdown of: A, 16.5%; B, 21%; C, 20%; and D, 14.5% (p=NS). No impact of donor serum sodium levels was seen on early post-operative results or on long-term outcome, indicating that cardiac allografts from donors with elevated sodium levels may be transplanted successfully with favorable results.

Effects of heparin-mediated extracorporeal low-density lipoprotein precipitation beyond lowering proatherogenic lipoproteins--reduction of circulating proinflammatory and procoagulatory markers.

In addition to hypercholesterolemia, proinflammatory and prothrombotic markers have been suggested to play an important role in atherogenesis. We examined whether heparin-mediated extracorporeal low-density lipoprotein precipitation (HELP) therapy modulates the circulating levels of proinflammatory and prothrombotic markers. Twenty-two coronary heart disease (CHD) patients undergoing regular HELP-apheresis (18 males, 4 females, mean age 57.3 +/- 10.9 years) were enrolled in this study. A single HELP therapy treatment significantly decreased the circulating levels of high sensitivity C-reactive protein (hs-CRP), soluble vascular adhesion molecule-1 (sVCAM-1), soluble E-selectin, lipopolysaccharide binding protein (LBP), endothelin-1 (ET-1), and monocyte chemoattractant protein-1 (MCP-1) on average by 67, 37, 24, 27, 24, and 15%, respectively. Prothrombotic factors including fibrinogen, tissue factor (TF), soluble CD40 ligand (sCD40L), and homocysteine were decreased by 66, 27, 16, and 22%, respectively. In accordance with previous studies HELP therapy reduced total cholesterol, low density lipoprotein (LDL) cholesterol, and Lp(a) mass by 50, 61, and 62%, respectively. Our data suggest that simultaneous reduction of proinflammatory and prothrombotic factors together with atherogenic lipoproteins by HELP-apheresis may contribute to improvement of endothelial dysfunction and thereby inhibit progression of atherosclerotic lesions and stabilize the existing plaque.

Tacrolimus or cyclosporine: which is the better partner for mycophenolate mofetil in heart transplant recipients?

BACKGROUND: The aim of this single-center study was to investigate whether trough level adjusted mycophenolate mofetil (MMF) is more efficacious in combination with tacrolimus (TAC) or cyclosporine (CsA) and to evaluate the impact of either drug on MMF dosage. METHODS: Sixty patients (TAC, n = 30; CsA, n = 30) undergoing heart transplantation were randomized into a prospective, open-label, controlled trial. Immunosuppression consisted of TAC or CsA in combination with MMF and corticosteroids. Target blood trough levels of TAC, CsA, and mycophenolic acid (MPA) were in the range of 10 to 15 ng/mL, 100 to 300 ng/mL, and 1.5 to 4.0 microg/mL, respectively. Acute rejection episodes (ARE); survival data; and adverse events with a special emphasis on infections, diabetes, hypertension, hypercholesterolemia, and the development of graft vessel disease (GVD) were recorded. RESULTS: Baseline characteristics were well balanced. All patients were successfully withdrawn from corticosteroids within 6 months of transplant. Freedom from acute rejection was significantly higher (P = 0.0001) and the incidence of ARE per 100 patient days significantly lower in the TAC-MMF group than in the CsA-MMF group (0.03 vs. 0.15; P = 0.00007). Overall patient survival during follow-up was similar (93% vs. 90%). To achieve the targeted MPA blood levels, a significantly lower dose of MMF was required for TAC versus CsA patients. After a follow-up time of 2 years, the mean GVD score was 1.85 +/- 3.18 in the TAC-MMF group and 3.95 +/- 4.8 in the CsA-MMF group (P = 0.08). CONCLUSIONS: At the selected doses and target levels for TAC and CsA used in this study, trough level adjusted MMF was more efficacious in combination with TAC for prevention of ARE. Furthermore, CsA patients need significantly more MMF to achieve similar MPA levels.

Heart transplantation: an approach to treating primary cardiac sarcoma?

Treating rare, primary cardiac soft-tissue sarcomas (C-STS) with heart transplantation (HTx) is controversial. Conventional tumor resection only partially alleviates the disease, and patients die of local recurrence of the tumor or of distant metastases. Heart transplantation offers the opportunity to eradicate the primary malignancy completely. In our experience of 4 patients with C-STS indicates, HTx followed by post-operative chemotherapy does not affect the long-term outcome. However, pre-operative chemotherapy can regress tumors in chemosensitive C-STS and potentially eradicate early micrometastases. Consecutive HTx for responders may then offer a chance of long-term survival.

Clinical results with an ePTFE inflow conduit for mechanical circulatory support.

BACKGROUND: Neurologic complication is an adverse event associated with mechanical circulatory support. To decrease the incidence of embolic cerebrovascular accidents (CVA) during support with the Novacor left ventricular assist system (LVAS), an expanded polytetrafluoroethylene (ePTFE) inflow conduit has been developed and introduced clinically. METHODS: Using clinical data from Europe and Canada, we conducted a retrospective analysis of the incidence of embolic CVA with the ePTFE inflow conduit (n=88) in comparison with the previously used polyester inflow conduits (n=310, including Vascutek n=155 and Cooley n=155). We calculated freedom from embolic CVA, risk reduction for embolic CVA, and linearized rates of embolic CVA. RESULTS: A significant decrease in the incidence of embolic CVA was demonstrated with the ePTFE conduit (ePTFE 10% vs polyester 23%, p=0.002). Kaplan-Meier analysis of freedom from embolic CVA at 180 days after implantation was 86% for the ePTFE group vs 72% for the polyester group (log-rank test, 0.0185). We also found an associated risk reduction of 55% in CVA occurrence in the ePTFE group when compared with the Polyester group (hazard ratio, 0.445; 95% confidence limit, 0.222-0.890; p=0.0221). Linearized CVA rates also were decreased at all time intervals after implantation in the ePTFE group. CONCLUSIONS: Preliminary clinical results with the newly introduced ePTFE inflow conduit provide compelling evidence that the ePTFE conduit material significantly decreases thromboembolic complications during mechanical circulatory support with the Novacor LVAS.

Professional parachuting: the risk of acute aortic dissection.

Acute aortic dissection is a rare disease, but if it occurs rapid diagnosis and therapy are needed. It is usually seen in elderly patients with long-term persistent arterial hypertension. In younger patients, it is mainly caused by congenital connective tissue disorders, such as Marfan syndrome, or by trauma. We present here a 34-year-old male patient with an acute type A aortic dissection. This patient was a professional parachutist and had carried out a large number of parachute jumps during his lifetime. He was admitted to the emergency department with acute chest pain. The symptoms were not related in time to a parachute jump. During a computed tomography scan, an aortic dissection was diagnosed. The patient was immediately referred to the operating room, and the ascending aorta was replaced by a conduit. After a regular postoperative course, the patient was discharged and recovered completely. Although acute aortic dissection is rare in young patients, it has to be considered in cases of acute chest pain. An immediate diagnosis and adequate therapy are essential to offer the patient a good clinical outcome and long-term survival.

A novel pulsatile bioreactor for mechanical stimulation of tissue engineered cardiac constructs.

After myocardial infarction, the implantation of stem cell seeded scaffolds on the ischemic zone represents a promising strategy for restoration of heart function. However, mechanical integrity and functionality of tissue engineered constructs need to be determined prior to implantation. Therefore, in this study a novel pulsatile bioreactor mimicking the myocardial contraction was developed to analyze the behavior of mesenchymal stem cells derived from umbilical cord tissue (UCMSC) colonized on titanium-coated polytetrafluorethylene scaffolds to friction stress. The design of the bioreactor enables a simple handling and defined mechanical forces on three seeded scaffolds at physiological conditions. The compact system made of acrylic glass, Teflon®, silicone, and stainless steel allows the comparison of different media, cells and scaffolds. The bioreactor can be gas sterilized and actuated in a standard incubator. Macroscopic observations and pressure-measurements showed a uniformly sinusoidal pulsation, indicating that the bioreactor performed well. Preliminary experiments to determine the adherence rate and morphology of UCMSC after mechanical loadings showed an almost confluent cellular coating without damage on the cell surface. In summary, the bioreactor is an adequate tool for the mechanical stress of seeded scaffolds and offers dynamic stimuli for pre-conditioning of cardiac tissue engineered constructs in vitro.

Coronary dilatation after heart transplantation.

BACKGROUND: The angiographic incidence of coronary dilatation (CD) in the nontransplant population is approximately 0.2% to 5%. The endothelial-dependent and -independent causes for CD are postulated. So far, the incidence and prognosis of CD after heart transplantation is unknown. METHODS: We retrospectively analyzed the annual coronary angiographies of 688 heart transplant recipients regarding the incidence of CD (defined as ≥1.5-fold localized increased vessel diameter or diffuse dilatation involving more than 50% of the coronary artery). A subgroup analysis of coronary epicardial (quantitative angiography) and microvascular (doppler flow measurement) vasomotor function in response to acetylcholine (endothelial dependent) and adenosine (endothelial independent) as well as intravascular ultrasound was performed in 177 patients. RESULTS: CD was detectable in 26 patients (3.8%) and was associated with stenosing coronary artery disease in 27% of the patients. Segments with CD tended to have less intimal hyperplasia compared with nondilated segments. A diffuse dilatation (type I-II) was present in 63% of the recipients. The right coronary artery was always involved. The patients with CD (5 of 177) showed a 31% reduced flow velocity in the dilated coronaries compared with the nondilated coronary arteries (P=0.03). Microvascular endothelial-independent function was impaired in CD by -29% (coronary flow reserve mean 1.9 vs. 2.7; P=0.04), whereas endothelial-dependent response was unchanged. Epicardial endothelial-dependent and -independent responses were not different between the groups. Incidence of CD was not associated with limited survival. CONCLUSION: The incidence of CD in the nontransplant population is similar to that in the transplanted population. However, the latter shows a more diffuse extent. Heart transplantation patients with CD had microvascular endothelial-independent functional limitations and flow deceleration, whereas survival was not affected.

Extracorporeal membrane oxygenation bridging to lung transplant complicated by heparin-induced thrombocytopenia.

In patients with acute respiratory failure and life-threatening impairment of pulmonary gas exchange, venovenous extracorporeal membrane oxygenation offers further therapeutic options. During extracorporeal membrane oxygenation treatment, systemic anticoagulation is usually achieved by heparin administration, which exposes patients to the risk of heparin-induced thrombocytopenia type II. We present a patient with acute respiratory distress syndrome on venovenous extracorporeal membrane oxygenation who experienced heparin-induced thrombocytopenia type II and in whom anticoagulation was continued with argatroban. Because respiratory failure did not resolve, the patient was bridged to lung transplant with extracorporeal membrane oxygenation. Argatroban anticoagulation was safely used until lung transplant (on day 114 after extracorporeal membrane oxygenation initiation) and after transplant in the presence of hepatic failure.

Heart-lung transplantation in patients with pulmonary atresia and ventricular septal defect.

OBJECTIVE: Heart-lung transplantation for patients with pulmonary atresia and ventricular septal defect is challenging. The aim of the study was to present a single-center experience with heart-lung transplantation in this difficult group of patients. METHODS: A retrospective review identified 9 patients aged 4.1 to 45.6 years (median, 25.4 years) with pulmonary atresia and ventricular septal defect who underwent heart-lung transplantation. Four (44.4%) patients had previous heart operations: 3 of them had palliative procedures (systemic-to-pulmonary shunts), and 1 had multistage correction. A standard transplantation method was used, with the exception of 1 patient with heterotaxy syndrome who underwent a modified operation. Major aortopulmonary collateral arteries were controlled by using various techniques. RESULTS: Follow-up ranged between 2 days and 12.6 years (median, 1.2 years). The hospital mortality rate was 22.2% (n = 2). In the late postoperative period, 3 patients died. The survival curve was similar to that of patients with other diagnoses undergoing heart-lung transplantation. The median length of intensive care unit stay was 58 days (range, 22-82 days), and the median length of hospital stay was 83 days (range, 35-136 days). The most common early complication was bleeding requiring re-exploration. In all cases the bleeding was proved to be from collateral vessels. CONCLUSIONS: Heart-lung transplantation in patients with pulmonary atresia and ventricular septal defect requires carefully planned and meticulously performed surgical intervention. This management should be taken into consideration as a future option if the specific anatomy is uncorrectable in early childhood, and the palliative procedures should be avoided.

Tacrolimus and mycophenolate mofetil as first line immunosuppression after lung transplantation.

The optimal maintenance therapy after lung transplantation remains to be established. The aim of this study was to analyse the impact of tacrolimus and mycophenolate mofetil (MMF) as first line immunosuppression on long-term survival and Bronchiolitis Obliterans Syndrome (BOS). From January 1996 through December 2006, all 155 recipients receiving tacrolimus and MMF as maintenance immunosuppression were included in this study. Tacrolimus and MMF was discontinued in 36 patients (23.2%). The overall survival rates were 91.6% at 6 months, 86.4% at 1 year, 74.9% at 3 years, 60.3% at 5 years and 32.4% at 10 years. The overall freedom from acute rejection was 74.6%, 63.2% and 59.4% at 1, 3, and 5 years respectively. The overall BOS-free survival was 95.6% at 1 year, 88.4% at 3 years, 69.5% at 5 years and 30.5% at 10 years. The development of BOS > or = 1 was associated with a significantly increased risk of death and reduced long-term survival. The combination of tacrolimus and MMF offers safe and reliable maintenance immunosuppression after lung transplantation. However, substantial improvements of long-term survival and freedom from BOS might only be achieved by a change in organ allocation policies and patient management beyond differential immunosuppressive protocols.

Detection of significant coronary artery stenosis with 64-slice computed tomography in heart transplant recipients: a comparative study with conventional coronary angiography.

PURPOSE: The present study evaluates clinical feasibility of cardiac multidetector computed tomography angiography (MDCTA) to detect significant stenosis of coronary vessels due to transplant vasculopathy (TVP) after heart transplantation (HTx). METHODS: Twenty-eight consecutive male HTx-recipients scheduled for their annual routine conventional coronary angiography (CCA) additionally underwent 64-slice MDCTA. RESULTS: Two patients were excluded from further MDCTA analysis. Out of 371 remaining coronary vessel segments evaluable by CCA, MDCTA was able to depict 302 (81.4%) in diagnostic image quality. On a segment based analysis, sensitivity, specificity, diagnostic accuracy (DA), negative predictive value (NPV), and positive predictive value (PPV) for detection of significant stenosis were calculated with 87.5%, 97.3%, 97.0%, 99.7%, and 46.7%, respectively. On a patient-based evaluation, sensitivity, specificity, DA, NPV, PPV were 100%, 81%, 84.6%, 100% and 55.6%, respectively. Evaluation of stenosis degree by MDCTA showed systematic overestimation of 4.4%. A moderate to good agreement comparing both modalities was found (Pearson's correlation coefficient: 0.64). CONCLUSION: High NPV suggesting 64-slice MDCTA being a reliable diagnostic tool for ruling out significant stenosis due to TVP in HTx patients. But its clinical value in these particular patients needs further investigation.

Assessment of cardiac allograft vasculopathy late after heart transplantation: when is coronary angiography necessary?

BACKGROUND: Cardiac allograft vasculopathy (CAV) represents a major prognostic factor in long-term survivors of heart transplantation (HTx). Reliable diagnosis of CAV late after HTx is important but remains the domain of invasive techniques such as coronary angiography. METHODS: To test alternative approaches, 54 consecutive HTx recipients (mean time since HTx: 52 months) were studied with intravascular ultrasound (IVUS), angiography, dobutamine stress echocardiography and immunofluorescence staining against anti-thrombin III (AT-III) in endomyocardial biopsies. Univariate and multivariate predictors as well as receiver-operating-characteristic (ROC) curves of different sets of predictors were calculated. RESULTS: Using IVUS as reference standard, CAV was present in 80% of subjects. Coronary angiography identified CAV correctly in only 44% of cases. If AT-III staining alone was used as a diagnostic criterion, CAV was correctly identified in 77% of subjects. In a multivariate analysis, only AT-III, donor age and echocardiography at rest emerged as independent predictors of CAV (p < 0.05 for all), yielding an excellent discriminative power. CONCLUSIONS: With almost equal reliability when compared with IVUS, CAV can be identified using information on donor age, wall motion score at rest and AT-III staining late after HTx. Coronary angiography may be limited to patients with a high probability score and should not be used routinely for surveillance of CAV.

Coronary endothelial vasomotor function and vascular remodeling in heart transplant recipients randomized for tacrolimus or cyclosporine immunosuppression.

OBJECTIVES: This study aimed to compare changes in coronary endothelial function, systemic endothelin-1 (ET-1) levels, and vascular remodeling in heart transplant recipients randomized to cyclosporin A (CyA) or tacrolimus (Tac) immunosuppression. BACKGROUND: Functional endothelial abnormalities and intimal thickening are sensitive measures of early cardiac allograft vasculopathy (CAV). METHODS: The randomized, prospective study was performed in two groups of 22 patients, maintained on Tac or CyA and mycophenolate mofetil immunosuppression, 1 and 12 months after heart transplantation. We investigated epicardial luminal diameter, coronary blood flow velocity, and ET-1 plasma levels at 1 and 12 months after transplantation. Structural coronary alterations were determined using intravascular ultrasound. RESULTS: Epicardial vasomotor function at baseline and during follow-up was comparable between the groups. Deterioration of microvascular endothelial function during follow-up was significantly enhanced in the CyA versus Tac group (p < 0.05). Circulating ET-1 concentration increased in the CyA group but significantly decreased over time in the Tac group (CyA +17% vs. Tac -25%; p < 0.05). The time-dependent increase in mean intimal area was significantly enhanced in the CyA versus Tac group, whereas the vessel area significantly increased during follow-up in the Tac compared with the CyA group. CONCLUSIONS: Epicardial endothelial function is comparable between CyA- and Tac-treated patients. Microvascular endothelial function deteriorates more in CyA-treated patients, a finding that correlates with enhanced ET-1 concentration and an increased intimal area during follow-up. The mean vessel area in the Tac group increased over time, indicating positive vascular remodeling. Tac is superior to CyA with respect to microvascular endothelial function, intimal thickening, and vascular remodeling.