Quantitative assessment of myocardial scar heterogeneity using cardiovascular magnetic resonance texture analysis to risk stratify patients post-myocardial infarction.

AIM: To determine whether heterogeneity of cardiac scar, as assessed by cardiovascular magnetic resonance (CMR) texture analysis, may provide insight into better risk stratification for patients with previous myocardial infarction (MI). MATERIALS AND METHODS: Patients with previous MI (n=76) were followed for a median of 371.5 days after late gadolinium enhancement (LGE) CMR. The primary endpoint was a composite of ventricular tachycardia, ventricular fibrillation, or unexplained syncope. Areas of LGE were identified and manually segmented on a short-axis projection. The characteristics of the scar heterogeneity were evaluated via CMR texture analysis. This is a filtration-histogram technique, where images are filtered using the Laplacian of a Gaussian filter to extract features different sizes (2-6 mm in radius) corresponding to fine, medium, and coarse texture scales followed by a quantification step using histogram analysis (skewness and kurtosis). RESULTS: Patients suffering arrhythmic events during the follow-up period demonstrated significantly higher kurtosis (coarse-scale, p=0.005) and lower skewness (fine-scale, p=0.046) compared to those suffering no arrhythmic events. Furthermore, Kaplan-Meier analysis showed significantly higher coarse kurtosis (p=0.004), and lower fine skewness (p=0.035) were able to predict increased incidence of ventricular arrhythmic events. CONCLUSIONS: In this pilot study, indices of texture analysis reflecting textural heterogeneity were significantly associated with a greater incidence of arrhythmic events. Further work is required to delineate the role of texture analysis techniques in risk stratification post-MI.

Mechanistic insights on ethanol dehydrogenation on Pd-Au model catalysts: a combined experimental and DFT study.

In this study, we have combined ultra-high vacuum (UHV) experiments and density functional theory (DFT) calculations to investigate ethanol (EtOH) dehydrogenation on Pd-Au model catalysts. Using EtOH reactive molecular beam scattering (RMBS), EtOH temperature-programmed desorption (TPD), and DFT calculations, we show how different Pd ensemble sizes on Au(111) can affect the mechanism for EtOH dehydrogenation and H2 production. The Au(111) surface with an initial coverage of 2 monolayers of Pd (2 ML Pd-Au) had the highest H2 yield. However, the 1 ML Pd-Au catalyst showed the highest selectivity and stability, yielding appreciable amounts of only H2 and acetaldehyde. Arrhenius plots of H2 production confirm that the mechanisms for EtOH dehydrogenation differed between 1 and 2 ML Pd-Au, supporting the perceived difference in selectivity between the two surfaces. DFT calculations support this difference in mechanism, showing a dependence of the initial dehydrogenation selectivity of EtOH on the size of Pd ensemble. DFT binding energies and EtOH TPD confirm that EtOH has increasing surface affinity with increasing Pd ensemble size and Pd coverage, indicating that surfaces with more Pd are more likely to induce an EtOH reaction instead of desorb. Our theoretical results show that the synergistic influence of atomic ensemble and electronic effects on Pd/Au(111) can lead to different H2 association energies and EtOH dehydrogenation capacities at different Pd ensembles. These results provide mechanistic insights into ethanol's dehydrogenation interactions with different sites on the Pd-Au surface and can potentially aid in bimetallic catalyst design for applications such as fuel cells.

Noninvasive Imaging of Activated Complement in Ischemia-Reperfusion Injury Post-Cardiac Transplant.

Ischemia-reperfusion injury (IRI) is inevitable in solid organ transplantation, due to the transplanted organ being ischemic for prolonged periods prior to transplantation followed by reperfusion. The complement molecule C3 is present in the circulation and is also synthesized by tissue parenchyma in early response to IRI and the final stable fragment of activated C3, C3d, can be detected on injured tissue for several days post-IRI. Complement activation post-IRI was monitored noninvasively by single photon emission computed tomography (SPECT) and CT using (99m) Tc-recombinant complement receptor 2 ((99m) Tc-rCR2) in murine models of cardiac transplantation following the induction of IRI and compared to (99m) Tc-rCR2 in C3(-/-) mice or with the irrelevant protein (99m) Tc-prostate-specific membrane antigen antibody fragment (PSMA). Significant uptake with (99m) Tc-rCR2 was observed as compared to C3(-/-) or (99m) Tc-PSMA. In addition, the transplanted heart to muscle ratio of (99m) Tc-rCR2 was significantly higher than (99m) Tc-PSMA or C3(-/-) . The results were confirmed by histology and autoradiography. (99m) Tc-rCR2 can be used for noninvasive detection of activated complement and in future may be used to quantify the severity of transplant damage due to complement activation postreperfusion.

Whole-body imaging of adoptively transferred T cells using magnetic resonance imaging, single photon emission computed tomography and positron emission tomography techniques, with a focus on regulatory T cells.

Cell-based therapies using natural or genetically modified regulatory T cells (T(regs)) have shown significant promise as immune-based therapies. One of the main difficulties facing the further advancement of these therapies is that the fate and localization of adoptively transferred T(regs) is largely unknown. The ability to dissect the migratory pathway of these cells in a non-invasive manner is of vital importance for the further development of in-vivo cell-based immunotherapies, as this technology allows the fate of the therapeutically administered cell to be imaged in real time. In this review we will provide an overview of the current clinical imaging techniques used to track T cells and T(regs) in vivo, including magnetic resonance imaging (MRI) and positron emission tomography (PET)/single photon emission computed tomography (SPECT). In addition, we will discuss how the finding of these studies can be used, in the context of transplantation, to define the most appropriate T(reg) subset required for cellular therapy.

Increased incidence and mortality associated with skin cancers after cardiac transplant.

Skin cancer incidence has been shown to be increased in the context of transplant-associated immunosuppression. There is, however, limited information specifically about the incidence of skin cancer after cardiac transplantation in the United States. A 10-year retrospective cohort study of 6271 heart transplants at 32 US transplant centers revealed increased postprocedure incidence of nonmelanoma and melanoma skin cancers, especially cutaneous squamous cell carcinoma, for which the incidence increased from 4- to 30-fold compared to the age and gender equivalent general population. Incidence of skin cancer in this study was consistent with prior single-center data regarding cardiac transplant patients. Comparison of all-cause mortality statistics for patients with basal cell carcinoma, squamous cell carcinoma and melanoma, respectively, demonstrated increased mortality associated with melanoma. Skin cancer screening and prophylaxis may be of some utility in reducing morbidity and mortality in cardiac transplant patients.

SPECT/CT lymphoscintigraphy of heterotopic cardiac grafts reveals novel sites of lymphatic drainage and T cell priming.

The normal function of lymphatic vessels is to facilitate the trafficking of antigen presenting cells to draining lymph nodes where they evoke an immune response. Donor lymphatic vessels are not connected to that of recipients' during organ transplantation. The pathophysiology of this disruption has received little attention. Murine heterotopic cardiac transplantation has been used extensively in transplantation research. Following vascularized organ transplantation, the main site of allosensitization is thought to be in the spleen of the recipient as a result of migration of donor passenger leukocytes via blood. Here, using Single Photon Emission Computed Tomography/Computerized Tomography (SPECT/CT) lymphoscintigraphy, we studied the pattern of lymphatic flow from mouse heterotopic abdominal cardiac grafts and identified mediastinal lymph nodes as the draining nodes for the donor graft. Staining with HY tetramer after transplantation of HY mismatched heart grafts and ELISPOT following allogeneic grafts to detect donor specific T cells revealed them as important sites for allosensitization. Our data indicates that mediastinal lymph nodes play a crucial role in the alloimmune response in this model, and should be used for ex vivo and adoptive transfer studies after transplantation in addition to the spleen.

The UNC-112 gene in Caenorhabditis elegans encodes a novel component of cell-matrix adhesion structures required for integrin localization in the muscle cell membrane.

Embryos homozygous for mutations in the unc-52, pat-2, pat-3, and unc-112 genes of C. elegans exhibit a similar Pat phenotype. Myosin and actin are not organized into sarcomeres in the body wall muscle cells of these mutants, and dense body and M-line components fail to assemble. The unc-52 (perlecan), pat-2 (alpha-integrin), and pat-3 (beta-integrin) genes encode ECM or transmembrane proteins found at the cell-matrix adhesion sites of both dense bodies and M-lines. This study describes the identification of the unc-112 gene product, a novel, membrane-associated, intracellular protein that colocalizes with integrin at cell-matrix adhesion complexes. The 720-amino acid UNC-112 protein is homologous to Mig-2, a human protein of unknown function. These two proteins share a region of homology with talin and members of the FERM superfamily of proteins. We have determined that a functional UNC-112::GFP fusion protein colocalizes with PAT-3/beta-integrin in both adult and embryonic body wall muscle. We also have determined that UNC-112 is required to organize PAT-3/beta-integrin after it is integrated into the basal cell membrane, but is not required to organize UNC-52/perlecan in the basement membrane, nor for DEB-1/vinculin to localize with PAT-3/beta-integrin. Furthermore, UNC-112 requires the presence of UNC-52/perlecan and PAT-3/beta-integrin, but not DEB-1/vinculin to become localized to the muscle cell membrane.

Earth and Mars: evolution of atmospheres and surface temperatures.

Solar evolution implies, for contemporary albedos and atmospheric composition, global mean temperatures below the freezing point of seawater less than 2.3 aeons ago, contrary to geologic and paleontological evidence. Ammonia mixing ratios of the order of a few parts per million in the middle Precambrian atmosphere resolve this and other problems. Possible temperature evolutionary tracks for Earth and Mars are described. A runaway greenhouse efect will occur on Earth about 4.5 aeons from now, when clement conditions will prevail on Mars.

Mapping evidence from systematic reviews regarding adult attachment and mental health difficulties: a scoping review.

OBJECTIVE: The aim of this scoping review was to map evidence gathered through systematic reviews regarding adult attachment and mental health difficulties. This review highlights established, emerging, and inconsistent findings, suggesting areas for future research, and implications for theory and practice. METHODS: A systematic search for meta-analyses and systematic reviews measuring adult attachment and concerning mental health difficulties was conducted. In total, 17 studies met the selection criteria. RESULTS: Findings were presented according to four identified themes, (1) measurement of attachment; (2) measurement of mental health difficulty; (3) intrapersonal processes related to attachment and mental health difficulties; and (4) interpersonal processes related to attachment and mental health difficulties. CONCLUSIONS: This review highlights the connection between attachment style and mental health difficulties, and suggests that relationships can facilitate both mental health and illheath. However, the mechanisms through which insecure attachment confers risk for mental health difficulties require further research.

Soil quality and barley growth as influenced by the land application of two compost types.

Agricultural use of organic residues offers an attractive method for their safe disposal and a valuable source of organic amendments and nutrients. A field experiment was conducted to investigate the influences of 0, 25, 50 and 100 t/ha spent mushroom compost (SMC), forced aeration compost (FAC) and inorganic fertilizer on soil properties and yield of barley (Hordeum vulgare). The considered soil properties (0-15 cm), after a growing season, included pH, EC, available P, Kjeldahl N, available cations, DTPA extractable elements, soil OC content, and bulk density and grain yield was also determined. Application of organic materials increased organic status of the soil and nutrient content. The effectiveness of the two composts on improving the productivity of the soil varied. SMC produced strongest correlations between soil nutrient levels and plant yield. Neither compost raised soil copper and zinc to levels that were of concern and high application rates decreased iron content.

Utilization of spent mushroom compost for the revegetation of lead-zinc tailings: effects on physico-chemical properties of tailings and growth of Lolium perenne.

In an attempt to promote sustainable vegetation cover on metalliferous tailings, a randomized factorial greenhouse trial of six-month duration was established to determine the effect of spent mushroom compost (SMC) amendment on the physical and chemical properties of the predominantly lead/zinc tailings. The tailings originated from the surface (20-30cm) of the partially-vegetated 76ha tailings management facility (TMF), where more than nine million tonnes of pyritic metalliferous material were deposited in an unlined land impoundment. SMC was incorporated at application rates of 0, 50, 100, 200 and 400tonha(-1), with each treatment replicated 10 times and Lolium perenne sown at a rate of 200kgha(-1). The addition of SMC was beneficent as a growing medium through improvement of the structural status of the tailings and ultimately through the provision of plant nutrients and reduction in metal concentrations. However, this improvement in the structural and chemical status of the tailings is not adequate in maintaining a sustainable vegetation cover and therefore other remedial options such as introducing a capillary break on the surface of the tailings facility are necessary.

Composition variability of spent mushroom compost in Ireland.

Spent mushroom compost (SMC) has proven to be an attractive material for improving soil structure in tilled soils and increasing dry matter production in grassland soils, owing to its high organic matter content and availability of essential plant nutrients. Because of this, it is important to identify the variability in composition of SMC in order to evaluate its merit as a fertilizer/soil conditioner. For this reason, a study was carried out involving the analysis of SMC samples obtained from five mushroom growers using compost from each of the 13 mushroom composting yards currently operating in both Northern Ireland (5 yd) and the Republic of Ireland (8 yd). The selected parameters measured include dry matter, organic matter, total N, P and K, C/N ratio; plant-available P and K, pH, EC, total Ca, Mg, Na, Cu, Zn, Fe, Mn, Cd, Cr, Ni, Pb; and cellulose, hemicellulose and lignin constituents. Yield of mushroom data were also collected from the selected growers. There were significant differences (P<0.05) within two compost production yards for some parameters, therefore, for the most part, the uniformity of SMC within each yard is relatively consistent. However, significant differences (P<0.05) were evident when comparing SMC obtained from growers supplied with compost from Northern Ireland and the Republic of Ireland independently, particularly among total and available phosphorus and potassium values. The results obtained show that, while SMC has fertilizer merit, its variability of composition must be taken into account when assessing this value. The variability of composition is also of particular interest in the context of recent emphasis on plant nutrient management in agriculture.

Internet use among young people with and without mental health difficulties.

OBJECTIVES: Research regarding adolescent internet use and mental health is sparse. However, awareness of a young person's internet use is becoming increasingly recognised as an important element of clinical assessment and intervention, and requires the development of an evidence base. The aim of the present study was to better understand the internet use of young people experiencing mental health difficulties and to contrast it with those who currently report no concerns. METHOD: In total, 299 young people aged 12-19 years, across a continuum of mental health difficulties, completed an online survey measuring internet use and related experiences. Young people were assigned to four groups: (a) attending inpatient services; (b) attending outpatient services; (c) a community group with mental health concerns and no clinical support; and (d) a regular community group. RESULTS: Those in the inpatient and outpatient groups visited more potentially harmful websites. Young people attending inpatient and outpatient services showed aspects of both more risky and less risky use. The community group reporting no mental health difficulties showed least risky use. The group experiencing difficulties but not receiving support showed consistently high risky use, suggesting this is a particularly vulnerable group. CONCLUSIONS: Despite methodological limitations, findings suggest that those with mental health difficulties may experience more of the risks and fewer of the benefits offered by the internet. Though further research is needed to clarify these findings, clinicians should consider routine assessment of Internet use when planning interventions for young people experiencing mental health difficulties.

Complex patterns of alternative splicing mediate the spatial and temporal distribution of perlecan/UNC-52 in Caenorhabditis elegans.

The unc-52 gene encodes the nematode homologue of mammalian perlecan, the major heparan sulfate proteoglycan of the extracellular matrix. This is a large complex protein with regions similar to low-density lipoprotein receptors, laminin, and neural cell adhesion molecules (NCAMs). In this study, we extend our earlier work and demonstrate that a number of complex isoforms of this protein are expressed through alternative splicing. We identified three major classes of perlecan isoforms: a short form lacking the NCAM region and the C-terminal agrin-like region; a medium form containing the NCAM region, but still lacking the agrin-like region; and a newly identified long form that contains all five domains present in mammalian perlecan. Using region-specific antibodies and unc-52 mutants, we reveal a complex spatial and temporal expression pattern for these UNC-52 isoforms. As well, using a series of mutations affecting different regions and thus different isoforms of UNC-52, we demonstrate that the medium NCAM-containing isoforms are sufficient for myofilament lattice assembly in developing nematode body-wall muscle. Neither short isoforms nor isoforms containing the C-terminal agrin-like region are essential for sarcomere assembly or muscle cell attachment, and their role in development remains unclear.

Enzymatic hydrolysis of organic waste materials in a solid-liquid system.

In the current climate of increasing emphasis on environmental protection and efficient waste management, regional management bodies and environmental agencies are striving to achieve an economical and environmentally acceptable system for the recycling of biodegradable organic wastes. Composting would appear to be a cost effective solution to this problem, but in its entirety, composting is an inherently lengthy and variable process and is restrictive in terms of the demand on resources and space in composting plants. The aim of this study was to compare a biological composting process of solid residues with an enzymatic hydrolysis process of residues. The length of time required to naturally compost three organic materials, spent mushroom compost (SMC), farmyard manure (FYM) and dairy wastewater sludge (DWS) under optimal conditions was 42 days, 98 days and 84 days, respectively. In an attempt to accelerate this process, commercial enzymes were added to the waste products in a heterogeneous solid-liquid system. The enzymes utilised included a range of proteases, cellulases, ligninases, lipases and pectinases, which are responsible for the hydrolysis of protein, cellulose, lignin, lipids and carbohydrates, respectively. Preliminary results indicate that all of the organic materials were stabilised within 9h and that the enzymes used would, therefore, improve the efficiency of a waste management plant, if such a system were employed. Spent mushroom compost has a mean N/P/K ratio of 20:10:10 recorded for composted SMC, while a similar ratio of 20:10:20 was obtained for hydrolysed SMC. In contrast, composted farmyard manure has a N/P/K ratio of 30:0:30 and a ratio of 10:1:10 for hydrolysed FYM. Finally, composted DWS has a N/P/K ratio of 20:1:30 while DWS hydrolysate has a N/P/K ratio of 40:1:20, with the decrease in nitrogen in the composted DWS attributed to the addition of wood chippings and sawdust as a bulking agent. While all three materials have a considerable supply of plant nutrients, the variability in nutrients could be overlooked when employed as a soil amendment.

[18F]tetrafluoroborate-PET/CT enables sensitive tumor and metastasis in vivo imaging in a sodium iodide symporter-expressing tumor model.

Cancer cell metastasis is responsible for most cancer deaths. Non-invasive in vivo cancer cell tracking in spontaneously metastasizing tumor models still poses a challenge requiring highest sensitivity and excellent contrast. The goal of this study was to evaluate if the recently introduced PET radiotracer [18F]tetrafluoroborate ([18F]BF4-) is useful for sensitive and specific metastasis detection in an orthotopic xenograft breast cancer model expressing the human sodium iodide symporter (NIS) as a reporter. In vivo imaging was complemented by ex vivo fluorescence microscopy and γ-counting of harvested tissues. Radionuclide imaging with [18F]BF4- (PET/CT) was compared to the conventional tracer [123I]iodide (sequential SPECT/CT). We found that [18F]BF4- was superior due to better pharmacokinetics, i.e. faster tumor uptake and faster and more complete clearance from circulation. [18F]BF4--PET was also highly specific as in all detected tissues cancer cell presence was confirmed microscopically. Undetected comparable tissues were similarly found to be free of metastasis. Metastasis detection by routine metabolic imaging with [18F]FDG-PET failed due to low standard uptake values and low contrast caused by adjacent metabolically active organs in this model. [18F]BF4--PET combined with NIS expressing disease models is particularly useful whenever preclinical in vivo cell tracking is of interest.

Domain specific interaction in the XRCC1-DNA polymerase beta complex.

XRCC1 (X-ray cross-complementing group 1) is a DNA repair protein that forms complexes with DNA polymerase beta (beta-Pol), DNA ligase III and poly-ADP-ribose polymerase in the repair of DNA single strand breaks. The domains in XRCC1 have been determined, and characterization of the domain-domain interaction in the XRCC1-beta-Pol complex has provided information on the specificity and mechanism of binding. The domain structure of XRCC1, determined using limited proteolysis, was found to include an N-terminal domain (NTD), a central BRCT-I (breast cancer susceptibility protein-1) domain and a C-terminal BRCT-II domain. The BRCT-I-linker-BRCT-II C-terminal fragment and the linker-BRCT-II C-terminal fragment were relatively stable to proteolysis suggestive of a non-random conformation of the linker. A predicted inner domain was found not to be stable to proteolysis. Using cross-linking experiments, XRCC1 was found to bind intact beta-Pol and the beta-Pol 31 kDa domain. The XRCC1-NTD(1-183)(residues 1-183) was found to bind beta-Pol, the beta-Pol 31 kDa domain and the beta-Pol C-terminal palm-thumb (residues 140-335), and the interaction was further localized to XRCC1-NTD(1-157)(residues 1-157). The XRCC1-NTD(1-183)-beta-Pol 31 kDa domain complex was stable at high salt (1 M NaCl) indicative of a hydrophobic contribution. Using a yeast two-hybrid screen, polypeptides expressed from two XRCC1 constructs, which included residues 36-355 and residues 1-159, were found to interact with beta-Pol, the beta-Pol 31 kDa domain, and the beta-Pol C-terminal thumb-only domain polypeptides expressed from the respective beta-Pol constructs. Neither the XRCC1-NTD(1-159), nor the XRCC1(36-355)polypeptide was found to interact with a beta-Pol thumbless polypeptide. A third XRCC1 polypeptide (residues 75-212) showed no interaction with beta-Pol. In quantitative gel filtration and analytical ultracentrifugation experiments, the XRCC1-NTD(1-183)was found to bind beta-Pol and its 31 kDa domain in a 1:1 complex with high affinity (K(d) of 0.4-2.4 microM). The combined results indicate a thumb-domain specific 1:1 interaction between the XRCC1-NTD(1-159)and beta-Pol that is of an affinity comparable to other binding interactions involving beta-Pol.

Efficacy of broadcast and perimeter applications of S-methoprene bait on the red imported fire ant in grazed pastures.

The red imported fire ant, Solenopsis invicta (Buren), is a major pest in the United States because of its painful sting. Toxic bait has been an important management tool against fire ants, but site registrations prohibit applications of most baits on grazed pastures. Extinguish, containing the insect growth regulator methoprene, was selected for this study because it has a broad site registration that includes grazed pastures. The primary objective of this research was to evaluate the efficacy for control of red imported fire ants by using broadcast applications of methoprene bait at a label rate of 1,121 g/ha versus applications around the perimeter of a target area at the reduced rate of 280 g/ha. Grazed pastures in Lee County, Alabama, and Chambers County, Alabama, were selected for this study, with broadcast treatments, perimeter treatments, and controls replicated three times at each site. All mounds were counted and rated using the USDA population index before applications and then at 8 and 16 wk posttreatment. Perimeter applications did not significantly reduce S. invicta mound abundance, but bait treatments significantly reduced mound abundance at 16 wk posttreatment at site 1 where applications were conducted in early evening. However, broadcast applications were not effective at site 2 where treatments were conducted in early morning with warmer temperatures. Emergence of winged alates was observed at 12 wk posttreatment, followed by a high density of incipient mounds that may have masked the full treatment effect of methoprene applications at site 2. Methoprene bait was effective in reducing abundance of S. invicta only when full label rates were applied.

Asymmetry of right ventricular enlargement in response to tricuspid regurgitation.

BACKGROUND: Analysis of right ventricular adaptation to tricuspid regurgitation was studied in 10 heart transplant recipients following inadvertent endomyocardial biopsy disruption of the tricuspid apparatus. METHODS AND RESULTS: Echocardiography demonstrated progressive diastolic right ventricular cavity enlargement (19.5+/-5.0 to 30.3+/-5.4 cm(2), P<0.0002), with disproportionate elongation along the midminor axis (3.5+/-0.6 to 5. 0+/-0.5 cm, P<0.001). As the right ventricle remodeled to more spherical (and less elliptical) proportions, the end-diastolic right ventricular midminor axis/long axis ratio increased significantly from 0.52+/-0.10 to 0.68+/-0.07, P<0.005. CONCLUSIONS: Ventricular enlargement due to right ventricular volume overload results in disproportionate dilation along the free wall to septum minor axis.

Does heart transplantation confer additional benefit over medical therapy to patients who have waited > 6 months for heart transplantation?

OBJECTIVES: This study compared the survival of patients with heart failure who have waited > 6 months for heart transplantation with that patients who undergo heart transplantation after a similarly prolonged waiting period. BACKGROUND: There are little data describing outcome in patients with severe heart failure who have waited for extended periods of time on the heart transplant waiting list. METHODS: Sixty-three consecutive patients who spent > 6 months on the heart transplant waiting list were examined. Mean (+/- SD) age was 53 +/- 9 years, mean left ventricular ejection fraction was 19 +/- 6%, and all were taking digoxin and diuretic and vasodilator agents. Patients who underwent transplantation during the follow-up period were censored from the pretransplantation analysis, and their survival was examined as part of the posttransplantation phase of the study. RESULTS: Of the 63 original patients examined, 25 underwent transplantation, 10 during inotropic or mechanical circulatory support. The pretransplantation mortality rate was 6% at 6 months after the 6-month milestone on the waiting list, 12% at 12 months and 22% at 18 months. The posttransplantation mortality rate was 5% at 6 months, 10% at 12 months and 24% at 18 months. There were no differences in survival at any time between the two phases of the study. CONCLUSIONS: Survival of patients who have survived > 6 months on the heart transplant waiting list is generally good. Although heart transplantation did not appear to confer additional survival advantage over medical therapy, a large proportion of the patients who underwent transplantation were critically ill at the time of transplantation and would undoubtedly have died of progressive heart failure had they not undergone transplantation. We conclude that heart transplantation should still be considered a therapeutic alternative in patients with heart failure even after a prolonged waiting period on the heart transplant waiting list.