Tuberculous meningitis in a lung transplanted patient.

A 57-year-old female lung transplant recipient developed tuberculosis after quadruple maintenance immunosuppression for acute cellular rejection with respiratory compromise. Deteriorating neurological status led to cerebral imaging and lumbar puncture, which showed Mycobacterium tuberculosis. Tuberculous meningitis with elevated intracranial pressure was treated for 2 weeks on a neurosurgical ward, and intensive care therapy was necessary for another 2 weeks. Complete neurological recovery was achieved after 3 months.

Transcranial Doppler sound detection of cerebral microembolism during transapical aortic valve implantation.

OBJECTIVE: Transapical aortic valve implantation (TAVI) is a new method that might reduce the surgical risk of conventional surgical aortic valve replacement in very high-risk patients. Increased downstream microembolization is expected in transapical aortic valve implantation. However, whether it usually occurs, how often, and its clinical relevance are not known. We report the results of ultrasound microembolic signal detection in the middle cerebral artery during the procedure. METHODS: Fifty patients (mean age: 80 ± 5 years; mean EuroSCORE: 36 ± 13 %) underwent transapical aortic valve implantation. Intraoperative transcranial Doppler (TCD) sound examination of both middle cerebral arteries (MCA) was used to identify high-intensity transient signals (HITS) and microembolic signals (MES) during seven phases of the procedure. Pre- and postoperative computed tomography of the brain and clinical neurological examinations were performed preoperatively and daily during the first postoperative week. RESULTS: During the procedure, HITS [right MCA: 435 ± 922 (range 9-5765); left MCA: 471 ± 996 (range 24-6432)] and MES [right MCA: 78 ± 172 (range 1-955); left MCA: 62 ± 190 (range 2-1553)] were detected in all patients. Most of the MES were recorded during valvuloplasty [right MCA: 3 ± 5.6 (range 0-31); left MCA: 2 ± 4.9 (range 0-30)] and positioning of the prosthetic valve in the aortic position [right MCA: 6 ± 5 (range 0-22); left MCA: 2 ± 6.9 (range 0-38)]. Postoperatively, there were no clinical signs of new cerebral embolism. CONCLUSIONS: Cerebral microemboli were detected by intraoperative transcranial Doppler sound examinations in all patients during transapical aortic valve implantation. Most of the signals were detected during balloon valvuloplasty and delivery of the prosthetic valve.

[Improvements in implantable mechanical circulatory support systems : literature overview and update]. / Fortschritte bei implantierbaren mechanischen Kreislaufunterstüzungssystemen : Literaturübersicht und Update.

In recent years, ventricular assist devices (VAD) supporting the left (LVAD), the right (RVAD) or both ventricles (BVAD) have rapidly emerged as the standard of care for advanced heart failure patients. Both the numbers and ages of patients in which they are used are rising worldwide, especially when used as a permanent support (bridge to destination, BTD). Due to the continuing lack of donor organs, these devices now represent a viable alternative to bridge patients to transplantation (BTT), with a 1-year survival rate of 86%. BTD, especially in long-term support, might be a valid, and the sole, option for those patients in whom heart transplantation is contraindicated. Patient selection, pre- and intra-operative preparation, as well as the timing of VAD implantation are important factors critical to successful circulatory support. While BTT remains the goal in the majority of patients, the number of permanent VADs (i. e. BTD) is rising significantly. Although explantation of a VAD system as a bridge to recovery (BTR) can be considered in only a small number of patients, it represents a very special part of this therapy modality.

Diagnosis and treatment of post-transplantation lymphoproliferative disorder in pediatric heart transplant patients.

PTLD is a severe complication in transplant recipients. Detection of increased EBV load in the peripheral blood acts as a surrogate marker for increased risk of PTLD development. We analyzed the time course of the disease, its severity, the organs involved, and mortality rates in our institutional experience of pediatric heart transplantation. This paper identifies risk factors for PTLD and describes the different ways of diagnosing and treating the disease. PTLD was screened for in 146 pediatric heart transplant patients using a retrospective analysis in patients who received transplantation before 1998. Prospective determination was performed in 72/146 patients transplanted after 1998 within the post-transplant follow-up. The occurrence of PTLD with all interventions, including tapering of immunosuppression, surgery, viral monitoring, and antiviral interventions, was recorded. PTLD was diagnosed in 12/147 (8.2%) children at a mean age of 7.2 +/- 3.3 yr after a mean post-transplant period of 3.2 +/- 2.2 yr. PTLD manifested in: lymph nodes (n = 4), intestine (n = 3), tonsils and adenoids (n = 2), eye (n = 2), and lung (n = 1). It was diagnosed in 7/12 as a monomorphic B-cell lymphoma and in four patients as a monomorphic Burkitt lymphoma, a polymorphic B-cell lymphoma, a T-cell rich or angiocentric lymphoma (Liebow) and as reactive plasmacytic hyperplasia (early lesion), respectively. Histology was not possible in one patient with ocular manifestation. EBV association was 83%. Risk factors in the comparison with patients without PTLD were age at time of Tx, primary EBV infection after Tx, use of Azathioprine and >or=3 doses of ATG. CMV mismatch and CMV infection, rejection episodes and steroids were not risk factors. Despite reduction of immunosuppression, treatment consisted of surgical procedures to remove tumor masses (n = 6), Rituximab (n = 5), polychemotherapy (n = 3), antiviral (n = 1) and autologous T-cell therapy (n = 1). All patients demonstrated full remission without death related to PTLD or treatment at 3.9 (1.3-6.2) yr median follow-up time. The manifestation of PTLD in pediatric heart transplant recipients is associated with EBV infection and is predominantly in the form of a B-cell lymphoma. A tight and specific follow-up including early assessment of immunity status and specific therapeutic intervention to improve cellular immunity is warranted and may contribute to a significant reduction of PTLD-related morbidity and mortality.

European Contegra multicentre study: 7-year results after 165 valved bovine jugular vein graft implantations.

OBJECTIVE: The valved bovine conduit "Contegra" for RVOT reconstruction became available for clinical use within a 100 % source data monitored and echo core lab controlled prospective European Multicentre Study, carried out from 1999 to 2006. We present the results of this study. METHODS: A total of 165 Contegras were implanted in 8 centres. The mean patient age was 3.9 years (2 days - 18 years, median 2.0). Total follow-up was 687 patient years. Diagnoses included: tetralogy of Fallot (64 patients, 39 %), truncus arteriosus (50, 30 %), double outlet right ventricle (16, 10 %), aortic valve disease/Ross procedure (11, 7 %), pulmonary valve atresia (10, 6 %), transposition of the great arteries (10, 6 %), 4 other malformations (2 %). Previous procedures were: 82 patients (50 %) - none; 37 (22 %) - valved conduit implantation; 14 (8 %) aortopulmonary shunt; 6 (4 %) catheter intervention. Follow-up appointments which included standardised echocardiography investigations were scheduled at 1, 3, 6, and 12 months, then annually. We evaluated freedom from death, explantation, intervention, stenosis, insufficiency, and degeneration. Results were stratified by age, diagnosis group and conduit size. RESULTS: The 5-year freedom-from rates were: explantation - 90 % (for patients aged 1 to 10 years) and 68 % (for younger patients); endocarditis - over 92 %; catheter intervention - 74 % (patients with congenital malformations); stenosis - 75 % and more (any group); insufficiency - 50 % (12 and 14 mm diameter conduits); any event - 13 % (patients under 1 year), 58 % (1 to 10 years), 82 % (> 10 years). Trace or mild insufficiency was a frequent, but not progressive finding. Mild calcification was detected in only 8 examinations. CONCLUSIONS: The performance of the Contegra conduit compares well with that of homografts when used to reconstruct paediatric right ventricular outflow tracts.

Prediction of short-term outcomes in patients with idiopathic dilated cardiomyopathy referred for transplantation using standard echocardiography and strain imaging.

OBJECTIVE: We sought to evaluate the short-term prognostic value of echocardiography including two-dimensional (2D) strain imaging in patients with end-stage idiopathic dilated cardiomyopathy (IDCM). METHODS: To evaluate the short-term (6-month) prognostic value of different parameters used for the assessment of IDCM patients referred for heart transplantation, we performed at the baseline transthoracic echocardiography including 2D strain imaging, N-terminal pro-BNP measurements, and exercise testing for all patients included in the study. After 6 months, all parameters, including endsystolic strain (ESS), peak systolic strain rate (SSR(max)), early and late diastolic strain rates, their ratio (diastolic strain rate E [DSR(E)], dialostolic strain rate A [DSR(A)], diastolic strain rate E and A wave ratio [DSR(E/A)]), and systolic intraventricular dyssynchrony indexes (IVDSI) were tested for their prognostic value to predict a patient's outcome. RESULTS: At the baseline stable patients had significantly lower transmitral E and A wave ratio (E/A), DSR(E/A), higher DSR(A) values, longer transmitral E wave deceleration time (DcT), higher longitudinal ESS and SSR(max) values, lower systolic circumferential and longitudinal IVDSI. CONCLUSION: The highest sensitivity for rapid heart failure progression was shown by DcT <100 ms, E/A > 1.5, DSR(A) < 0.3/s, circumferential IVDSI > 0.16, and longitudinal IVDSI > 0.22 (91%, 78%, 94%, 83%, and 75%, respectively).

Pulmonary interstitial and vascular abnormalities following cardiac transplantation.

Impairment of pulmonary diffusion (KCO) is frequently seen in patients following orthotopic heart transplantation (HTX). To assess potential histomorphological pulmonary causes of KCO abnormalities, we evaluated tissue samples from 73 patients who succumbed after HTX in the presence of KCO abnormalities, excluding those with infectious or primary pulmonary causes of death. In 97% of subjects, we observed considerable histomorphological changes in interstitial or vascular tissue or both. In 32% of samples, interstitial changes (eg, cell proliferation or fibrosis) were accompanied by vascular abnormalities, whereas more than two-thirds of the patients showed alterations in one of the two conditions. Hemosiderin-laden macrophages were observed in 48% of subjects. The mean alveolar-capillary wall thickness was significantly increased to 9.9 +/- 4.2 mum. The time of survival after HTX was not correlated with the incidence of pathological findings. The described vascular and interstitial pulmonary changes as well as the increased membrane thickness may cause the persistent impairment of KCO after HTX.

Enteric-coated mycophenolate-sodium in heart transplantation: efficacy, safety, and pharmacokinetic compared with mycophenolate mofetil.

Mycophenolic acid (MPA) is an effective immunosuppressive treatment for renal transplant recipients, but its effective use and best practice are not established in cardiac transplantation. This multicenter, single-blind, randomized, parallel group clinical trial prospectively evaluated the therapeutic equivalence of enteric-coated mycophenolate-sodium (EC-MPS) versus mycophenolate mofetil (MMF) in combination with cyclosporine (CyA) and steroids as determined by the primary objective of treatment efficacy during the first 6 months of treatment in 154 de novo heart transplant recipients. Both groups received equivalent doses of MPA, either 720 mg b.i.d EC-MPS or 1000 mg b.i.d MMF. EC-MPS showed a comparable efficacy and safety profile compared with MMF with significantly less dose reduction. Treatment failure occurred in 57.7% and 60.5% with EC-MPS and MMF, respectively, EC-MPS was therapeutically equivalent to MMF in cardiac transplantation.

Early clinical experience with the E-vita thoracic stent-graft system: a single center study.

AIM: The aim of this study was to evaluate the safety and efficacy of a new endovascular thoracic stent-graft, which was designed to overcome the restrictions of previously used stent-grafts. METHODS: Between May 2004 and March 2008 a prospective evaluation was conducted in 126 consecutive patients (71% men; age 64 [19-86] years). A total of 138 implantations were performed. E-vita stent-grafts were implanted for type-B dissection (N.=56), degenerative aneurysm (N.=25), penetrating aortic ulcer (N.=17), blunt traumatic lesions (N.=10), mobile atheroma (N.=1), suture aneurysms (N.=7) and revisionary surgery following previous endograft implantation (N.=22). All patients eligible for stent-grafting were treated with this system regardless of their clinical status and aortic pathology. The percentage of emergency procedures was 52% (N.=72). Per implantation a mean of 1.3 segments was implanted with an effective total covered length of the aorta of mean 204 mm, median 230 mm (0-450 mm). In 32 of 39 cases with more than one segment, the entire descending aorta was included in the procedure. RESULTS: The 30-day mortality rate was 12.3% (17 patients). All deaths but one were in the group of emergency surgery patients. This results in mortality of 1.5% in the elective and 22% in the emergency procedures. Reversible procedure-induced spinal cord ischemia was observed in 2 cases. Stroke occurred in 2.8% (4 patients). Primary technical success was rated at 77 % (106 procedures) and secondary success at 89 % (124 procedures). CONCLUSION: All forms of thoracic aortic disease can be treated with this new stent-graft. It has proved particularly valuable in cases of difficult conditions in the aortic arch and extended aneurysms. In particular, it is possible to cover the entire thoracic aorta with two or three stent-graft segments, thus considerably reducing the number of connections.

Economic evaluation of everolimus and mycophenolate mofetil versus azathioprine in de novo heart transplantation.

UNLABELLED: Both the proliferation signal inhibitor everolimus (1.5 mg/day) and mycophenolate mofetil (MMF) (3 g/day) have shown superior efficacy versus azathioprine in de novo heart transplantation. The cost-effectiveness of everolimus and MMF versus azathioprine was assessed to 6 months posttransplantation. METHODS: The evaluation was performed from the German health insurance payer perspective. The composite efficacy endpoint in the everolimus trial was death, graft loss/retransplantation, biopsy-proven acute rejection (BPAR) grade>or=3A, rejection with hemodynamic compromise, and loss to follow-up. The composite endpoint in the MMF trial included only death, retransplantation, and BPAR with hemodynamic compromise. To mimic the everolimus endpoint, an estimated number of patients with BPAR>or=3A was added to the MMF trial results, using two mapping scenarios. RESULTS: The incremental 6-month cost versus azathioprine was euro2535 for everolimus and euro3007 for MMF. The absolute reduction in efficacy failure versus azathioprine was 10.4% for everolimus and 9.8% and 10.1% for MMF, respectively, using scenarios 1 and 2. The incremental cost per efficacy failure avoided (ie, the incremental cost versus azathioprine divided by the reduction in efficacy failure) was euro24,457 for everolimus, and euro30,628 and euro29,912 for MMF in scenarios 1 and 2. CONCLUSION: This analysis, based on findings from two clinical trials, suggested that everolimus was more cost-effective than MMF versus azathioprine in the first 6 months after heart transplantation. Data from a head-to-head trial are required to confirm these results.

Pseudoaneurysm after ICD battery replacement.

False aneurysms of the extracranial carotid arteries are rare and mainly of traumatic origin. We report on a patient who presented with a sudden onset mass in his right neck 2 weeks after routine replacement of his ICD battery. He had received systemic anticoagulation since an aortic valve replacement 5 years before. By color Doppler sonography the mass was identified as a partly thrombosed false aneurysm originating from the common carotid artery. As no spontaneous resolution occurred during the following days the aneurysm was removed surgically 5 days later without further complications. However no connection to the common carotid artery was found at surgery. Yet in the histopathological examination the specimen showed the morphological characteristics of a pseudoaneurysm. There was no history of neck-trauma and no attempted vascular access during the recent operation.

[Determination of ventricular volumes in coronary artery disease: comparison of two gated SPECT analysis tools with MRI]. / Bestimmung ventrikulärer Volumina bei koronarer Herzerkrankung: Vergleich zweier Gated-SPECT-Analyseverfahren mit MRT.

AIM: Comparison of two gated SPECT analysis tools -- gated SPECT quantification (GSQ) and emory cardiac toolbox (ECT) -- in patients with coronary artery disease (CAD) and severely impaired left ventricular function (preoperative: EF <35% by cardiac catheter). PATIENTS, METHODS: A total of 56 gated SPECT examinations (one-day hybrid-protocol with (201)Tl-chloride for rest and (99m)Tc-sestamibi for stress applied during low-dose dobutamine stress MR-examination; temporal resolution; 8 phases per cardiac cycle) were performed in 36 patients (31 preoperatively, 25 postoperatively) and compared with MRI in 48 cases. Left ventricular end-diastolic (LV-EDV) and end-systolic (LV-ESV) volumes as well as the left ventricular ejection fraction (LV-EF) were calculated. RESULTS: The total volumetric assessment by both analysis algorithms (n = 56) showed good intraclass correlation coefficients preoperatively (n = 31), but even better postoperatively (n = 25). The mean reconstruction time was approximately 3 minutes ( +/- 2 SD) for GSQ and 15 minutes ( +/- 5 SD) for ECT. In comparison to MRI the results of both analysis tools also correlated well, but the agreement decreased in the presence of scared tissue. The mean LV-EF (MRI) preoperatively was 30.4%, in 6/36 patients above the values calculated from cardiac catheter, postoperatively 34.6%. CONCLUSION: Both gated SPECT analysis tools showed reliable volumetric assessments in high-risk patients with CAD and severely reduced LV-EF in comparison to MRI, with advantages for GSQ in terms of postprocessing time. However, for the calculation of LV-EF a markedly lower concordance with MR-results was observed for both methods depending on the presence of myocardial scars.

Routine screening of donor hearts by coronary angiography is feasible.

BACKGROUND: Because of the shortage of donor hearts, the criteria for acceptance have been considerably extended. Meanwhile every fourth heart donor in Europe is over 50 years old. As we have previously demonstrated, transmission of preexisting coronary atherosclerosis (CAS) by means of transplantation is not rare. Transmitted CAS results in a 2- to 3-fold increased risk for early graft failure after heart transplantation (HTX). Nevertheless, in most cases donor angiograms are not considered feasible. METHODS: In May 2003 in the northeast region of the Deutsche Stiftung Organtransplantation (DSO-NO), we introduced the guideline that every donor over 40 years old must be screened by angiography. RESULTS: Up to May 2003, fewer than 5% of donors had been screened by angiography; this situation is the rule in most Eurotransplant regions at present. Since May 2003 in the DSO-NO region, 85% of all donors over 40 years old were screened by angiography. Seventy percent of all donor hospitals--offering 90% of all donors--had an angiography facility. The additional costs of approximately euro 800 per donor angiogram were compensated by fewer fruitless airplane missions when CAS was diagnosed by the surgeon on the spot, which cost on average about euro 5,000 each. In conclusion, from a logistical as well as from a financial point of view, almost comprehensive angiographic donor screening is feasible. It reduces the risk of a recipient suffering from early graft failure.

Lipoprotein binding to anionic biopolyelectrolytes and the effect of glucose on nanoplaque formation in arteriosclerosis and Alzheimer's disease.

Arteriosclerosis with its clinical sequelae (cardiac infarction, stroke, peripheral arterial occlusive disease) and vascular/Alzheimer dementia not only result in far more than half of all deaths but also represent dramatic economic problems. The reason is, among others, that diabetes mellitus is an independent risk factor for both disorders, and the number of diabetics strongly increases worldwide. More than one-half of infants in the first 6months of life have already small collections of macrophages and macrophages filled with lipid droplets in susceptible segments of the coronary arteries. On the other hand, the authors of the Bogalusa Heart Study found a strong increase in the prevalence of obesity in childhood that is paralleled by an increase in blood pressure, blood lipid concentration, and type 2 diabetes mellitus. Thus, there is a clear linkage between arteriosclerosis/Alzheimer's disease on the one hand and diabetes mellitus on the other hand. Furthermore, it has been demonstrated that distinct apoE isoforms on the blood lipids further both arteriosclerotic and Alzheimer nanoplaque formation and therefore impair flow-mediated vascular reactivity as well. Nanoplaque build-up seems to be the starting point for arteriosclerosis and Alzheimer's disease in their later full clinical manifestation. In earlier work, we could portray the anionic biopolyelectrolytes syndecan/perlecan as blood flow sensors and lipoprotein receptors in cell membrane and vascular matrix. We described extensively molecular composition, conformation, form and function of the macromolecule heparan sulfate proteoglycan (HS-PG). In two supplementary experimental settings (ellipsometry, myography), we utilized isolated HS-PG for in vitro nanoplaque investigations and isolated human coronary artery segments for in vivo tension measurements. With the ellipsometry-based approach, we were successful in establishing a direct connection on a molecular level between diabetes mellitus on the one side and arteriosclerosis/Alzheimer's disease on the other side. Application of glucose at a concentration representative for diabetics and leading to glycation of proteins and lipids, entailed a significant increase in arteriosclerotic and Alzheimer nanoplaque formation. IDLapoE4/E4 was by far superior to IDLapoE3/E3 in plaque build-up, both in diabetic and non-diabetic patients. Recording vascular tension of flow-dependent reactivity in blood substitute solution and under application of different IDLapoE isoforms showed an impaired vasorelaxation for pooled IDL and IDLapoE4/E4, thus confirming the ellipsometric investigations. Incubation in IDLapoE0/E0 (apoE "knockout man"), however, resulted in a massive flow-mediated contraction, also complemented by strongly aggregated nanoplaques. In contrast, HDL was shown to present a powerful protection against nanoplaque formation on principle, both in the in vitro model and the in vivo scenario on the endothelial cell membrane. The competitive interplay with LDL is highlighted through the flow experiment, where flow-mediated, HDL-induced vasodilatation remains untouched by additional incubation with LDL. This is due to the four times higher affinity for the proteoglycan receptor of HDL as compared to LDL. Taken together, the studies demonstrate that while simplistic, the ellipsometry approach and the endothelial-mimicking proteoglycan-modified surfaces provide information on the initial steps of lipoprotein-related plaque formation, which correlates with findings on endothelial cells and blood vessels, and afford insight into the role of lipoprotein deposition and exchange phenomena at the onset of these pathophysiologies.

Electron-beam computed tomography in the assessment of coronary artery disease after heart transplantation.

BACKGROUND: Our aim was to compare the electron-beam CT (EBCT) features of coronary arteries in heart transplant recipients with those of biplane coronary angiography and intracoronary ultrasound (ICUS). METHODS AND RESULTS: We examined 112 heart transplant recipients (25 female; age, 17 to 69 years; median, 52 years) 1 to 153 months (median, 46 months) after surgery by EBCT to detect coronary artery calcifications. Calcifications were quantified by the Agatston scoring system. EBCT scores were compared with coronary angiography in all patients and ICUS of the left anterior descending coronary artery (LAD) in 100 patients. Coronary artery calcifications were found in 84 patients (75%). Angiographically, 16 patients displayed >50% coronary artery stenoses, all of whom had some degree of coronary artery calcification and only 1 of whom had a score of <55 (P<0.0001). With this threshold, EBCT had a sensitivity of 94%, a specificity of 79%, a positive predictive value of 43%, and a negative predictive value of 99% for detecting stenosis. ICUS confirmed the presence of calcified plaques in all patients with an LAD score >9. EBCT total calcium score was associated with the degree of intimal proliferation in that patients without ICUS features of allograft vasculopathy had a median score of 0 (25th percentile, 0; 75th percentile, 0), whereas patients with Stanford class IV vasculopathy had a median score of 41 (9 to 98, P<0.0001). CONCLUSIONS: EBCT is a promising noninvasive test for the detection of coronary heart disease in cardiac transplant recipients.

Reliability of tissue Doppler wall motion monitoring after heart transplantation for replacement of invasive routine screenings by optimally timed cardiac biopsies and catheterizations.

BACKGROUND: Invasive screenings at predefined time intervals for acute rejection and transplant coronary artery disease (TxCAD) are standard procedures. However, cardiac biopsies and catheterizations are distressing and risky for the patients and are also costly. We assessed the reliability of pulsed-wave tissue Doppler imaging (PW-TDI) for the timing of invasive examinations in heart recipients in an attempt to avoid unnecessary endomyocardial biopsies (EMBs) and catheterizations. METHODS AND RESULTS: PW-TDI obtained at the basal left ventricular posterior wall before 408 EMBs and 293 catheterizations was tested for its diagnostic value regarding rejection and TxCAD with the use of International Society of Heart and Lung Transplantation biopsy grading, coronary angiography, and intravascular ultrasound as standards. Early diastolic peak wall motion velocity and relaxation time showed high sensitivities for clinically relevant rejection diagnosis (90.0% and 93.3%, respectively). The negative and positive predictive values for rejection of diastolic parameter changes appeared high enough (up to 96% and 92%, respectively) to allow a reliable noninvasive PW-TDI monitoring with efficiently timed, instead of routinely scheduled, EMBs. At definite cutoff values for systolic parameters, the probability for TxCAD reached 92% to 97%. The Fisher classification functions allowed TxCAD exclusion with 80% probability. CONCLUSIONS: Without diastolic parameter changes, acute rejection can be practically excluded, and serial PW-TDI can save patients from routine EMBs. The high specificity and negative predictive value for TxCAD of reduced systolic peak velocities and extended systolic time allow optimized timed catheterizations. Peak systolic velocity and systolic time allow diagnostic classifications that enable patients without known TxCAD but with high risk for catheterization to be spared routine angiographies.

Immunoglobulin adsorption in patients with idiopathic dilated cardiomyopathy.

BACKGROUND: Idiopathic dilated cardiomyopathy (IDC) frequently is a progressive disease without causative therapy options. Following the hypothesis that in certain patients autoantibodies against cardiac structures may induce, maintain, or promote the progression of the disease, we investigated whether the elimination of these autoantibodies through immunoadsorption would improve cardiac function. METHODS AND RESULTS: This prospective case-control study included 34 patients with IDC. Each patient presented with moderate to severe heart failure and evidence of autoantibodies directed against beta(1)-adrenoceptors (beta(1)-AABs). Seventeen patients received standard medical therapy (control group), whereas 17 were also treated with immunoadsorption (treatment group) to eliminate beta(1)-AABs. A 1-year follow-up included echocardiographic assessment of left ventricular ejection fraction and internal diameters, beta(1)-AAB levels, and clinical status every 3 months. Within 1 year, the mean+/-SD left ventricular ejection fraction rose from 22.3+/-3.3% to 37.9+/-7.9% (P=0.0001) in the treatment group, with a relative increase of 69.9%. However, in the control group, no overall increase was seen (from 23.8+/-3.0% to 25.2+/-5.9%, P=0. 3154). Left ventricular diameter in diastole decreased by 14.5% from 74.5+/-7.1 to 63.7+/-6.0 mm in the treatment group (P=0.0001) and by 3.8% (P=0.2342) in the control group. In the treatment group, the NYHA functional rating improved after immunoadsorption (P=0.0001). beta(1)-AABs did not increase anew. CONCLUSIONS: In IDC, the use of immunoadsorption is superior to the use of standard medical therapy. It significantly improves cardiac performance and clinical status.

Pulsatile flow in patients with a novel nonpulsatile implantable ventricular assist device.

BACKGROUND: Ventricular assist devices (VADs) are an accepted therapy for patients with end-stage heart failure. The implantable devices that are available produce a pulsatile flow and are very large. In 6 patients, beginning in November 1998, we started to use the continuous-flow implantable DeBakey VAD device, which weighs 93 g. To detect the flow in peripheral vessels, we measured transcranial Doppler signals in patients after implantation. METHODS AND RESULTS: Transcranial Doppler studies were performed with the MULTI-DOP X4 device with two 2-MHz probes (for the middle cranial arteries) in 4 patients for up to 12 weeks twice weekly after implantation. The blood velocity was measured, and the pulsation index (PI) calculated. The measured pump flow and rotations per minute were registered. The preoperative echocardiographic assessment values were compared with those acquired 6 weeks after implantation. The PI increased continually in all patients after VAD implantation, left ventricular (LV) ejection fraction did not improve, but right ventricular (RV) ejection fraction after implantation improved compared with preoperative values. The LV end-diastolic diameter after implantation decreased between 11% and 46% intraindividually. There was no correlation between PI and blood pressure or, except in 1 patient, between PI and blood flow through the VAD. CONCLUSIONS: The DeBakey VAD unloads the LV, which leads to a decrease in LV end-diastolic LV diameter and to the restoration of RV function. The unloaded LV and partially recovered RV provide a nearly physiological pulsatile flow despite the continuous flow of the VAD. Pulsatility is independent of peripheral vascular resistance. The first clinical experience with the DeBakey VAD was positive and has resulted in its continued use.

Changes in surface expression of platelet membrane glycoproteins and progression of heart transplant vasculopathy.

BACKGROUND: Transplant vasculopathy is the main limiting factor of the long-term success of heart transplantation. We sought to establish the role of platelets in the development and progression of transplant vasculopathy. METHODS AND RESULTS: Platelet analysis and intracoronary ultrasound examination were performed in 78 heart transplant recipients. Quantitative intracoronary ultrasound was used to define the severity of disease at baseline (48.8+/-4.5 months after transplantation) and at 1-year follow-up. Platelet activation was assessed with the use of immunological surface markers of activation (ligand-induced binding site 1 [LIBS-1], P-selectin, GPIIb-IIIa) and flow cytometry. We found that LIBS-1 immunoreactivity was significantly increased in patients with diffuse disease when compared with focal transplant disease (median [quartile], 27[14, 64] versus 18[7.9, 47], P=0.04). In a logistic regression model, we found that LIBS-1 was an independent predictor for the presence and progression of diffuse transplant vasculopathy (P=0.04). Patients with enhanced LIBS-1 levels (>75% quartile) had a 3.3-fold increased relative risk (95% CI 1.8 and 18.9, P=0.002) for the presence of diffuse transplant vasculopathy. When a cutoff value of 16.5 for the level of LIBS-1 was used, patients had a 4.8-fold increased relative risk (95% CI 1.9 and 12.5, P<0.01) for the progression of transplant vasculopathy. CONCLUSIONS: Enhanced platelet activation is strongly associated with the development and progression of transplant vasculopathy. Understanding the underlying pathophysiological mechanisms might contribute to the development of treatment strategies to prevent transplant vasculopathy.

Procalcitonin, a donor-specific predictor of early graft failure-related mortality after heart transplantation.

BACKGROUND: To date, donor-specific markers to predict outcome after heart transplantation (HTx) are unknown. Increased procalcitonin (PCT) levels have been found in infectious inflammation with systemic reactions and/or poor organ perfusion but have not been studied in heart donors. We evaluated PCT as a predictor of early graft failure-related mortality after HTx. METHODS AND RESULTS: PCT and C-reactive protein (CRP) serum concentrations were measured in samples collected immediately before pericardium opening from 81 consecutive brain-dead multiple-organ donors. Donors for high-urgency-status recipients (n=2) were excluded from analysis. The remaining donors were retrospectively divided into 2 groups: donors for recipients who died within 30 days after HTx, after an early graft failure (group II, n=8), and all other donors (group I, n=71). No differences in donor and recipient demographic characteristics were found between groups. Areas under the receiver operating characteristic curves for graft failure-related mortality were 0.71 for PCT and 0.64 for CRP. A PCT value >2 ng/mL as a predictor of graft failure-related mortality had a specificity of 95.8% and sensitivity of 50.0%. The odds ratio for graft failure-related mortality for recipients of hearts from donors with PCT levels >2 ng/mL was 22.7 (unadjusted, 95% CI 3.7 to 137.8, P=0.0007) and 43.8 (after adjustment for prespecified potential confounders, 95% CI 1.4 to 1361.0, P=0.031). CONCLUSIONS: A PCT level >2 ng/mL in a cardiac donor at the time of explantation appears to predict early graft failure-related mortality.