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1.
  • Abbey, Susan E., et al. (author)
  • Qualitative interviews versus standardised self-report questionnaires in assessing qualityb of life in heart transplant recipients
  • 2011
  • In: The Journal of Heart and Lung Transplantation. - : Elsevier. - 1053-2498 .- 1557-3117. ; 30:8, s. 963-966
  • Journal article (peer-reviewed)abstract
    • Quality of life (QoL) studies in heart transplant recipients (HTRs) using validated, quantitative, self-report questionnaires have reported poor QoL in approximately 20% of patients. This consecutive mixed methods study compared self-report questionnaires, the Medical Outcomes Study 36-item Short Form Health Survey (MOS SF-36) and the Atkinson Life Satisfaction Scale, with phenomenologically informed audiovisual (AV) qualitative interview data in 27 medically stable HTRs (70% male; age 53 ± 13.77 years; time since transplant 4.06 ± 2.42 years). Self-report questionnaire data reported poor QoL and more distress compared with previous studies and normative population samples; in contrast, 52% of HTRs displayed pervasive distress according to visual methodology. Using qualitative methods to assess QoL yields information that would otherwise remain unobserved by the exclusive use of quantitative QOL questionnaires.
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  • Andersson Sjöland, Annika, et al. (author)
  • Fibroblast phenotypes and their activity are changed in the wound healing process after lung transplantation.
  • 2011
  • In: The Journal of Heart and Lung Transplantation. - : Elsevier BV. - 1557-3117 .- 1053-2498. ; 30, s. 945-954
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Lung transplantation (LTx) is established as a life-saving treatment in end-stage lung disease. However, long-term survival is hampered by the development of chronic rejection, almost synonymous with bronchiolitis obliterans syndrome (BOS). The rejection is characterized by deposition of extracellular matrix in small airways. Fibroblasts/myofibroblasts are the main producers of extracellular matrix molecules such as proteoglycans. This study compared fibroblast phenotype and activity in the wound healing process at different points after LTx in patients who later did, or did not, develop BOS. METHODS: Distally derived fibroblasts from patients 6 and 12 months after LTx and from healthy controls were analyzed for production of the proteoglycans versican, perlecan, biglycan, and decorin, with and without transforming growth factor (TGF)-β(1). Fibroblast migration and proliferation were also studied. RESULTS: At 6 and 12 months after LTx, versican production was higher in fibroblasts from LTx patients (p < 0.01 p < 0.01) than from controls. Fibroblasts from patients who later developed BOS were more responsive to TGF-β(1)-induced synthesis of versican and biglycan than patients without signs of rejection (p < 0.05). Production of perlecan and decorin was negatively correlated with fibroblast proliferation in fibroblasts at 6 months after LTx. In a more detailed case study of 2 patients, one with and one without BOS, the altered proteoglycan profile was associated with impaired lung function. CONCLUSIONS: LTx changes the phenotype of fibroblasts to a non-proliferative but extracellular matrix-producing cell due to wound healing involving TGF-β(1). If not controlled, this may lead to development of BOS.
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  • Arora, Satish, et al. (author)
  • Improvement in renal function after everolimus introduction and calcineurin inhibitor reduction in maintenance thoracic transplant recipients: The significance of baseline glomerular filtration rate
  • 2012
  • In: The Journal of Heart and Lung Transplantation. - : Elsevier. - 1053-2498 .- 1557-3117. ; 31:3, s. 259-265
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: The NOCTET (NOrdic Certican Trial in HEart and lung Transplantation) trial demonstrated that everolimus improves renal function in maintenance thoracic transplant (FIX) recipients. Nevertheless, introduction of everolimus is not recommended for patients with advanced renal failure. We evaluated NOCTET data to assess everolimus introduction amongst TTx recipients with advanced renal failure. less thanbrgreater than less thanbrgreater thanMETHODS: This 12-month multicenter Scandinavian study randomized 282 maintenance TTx recipients to everolimus introduction with calcineurin inhibitor (CNI) reduction or standard CNI therapy. The measured glomerular filtration rate (mGFR) was noted at baseline and after 1-year using Cr-ethylenediarninetetraacetic acid clearance. less thanbrgreater than less thanbrgreater thanRESULTS: In 21 patients with a baseline mGFR of 20 to 29 ml/min/1.73 m(2), renal function improved in the everolimus group compared with the control group ((Delta mGFR 6.7 +/- 9.0 vs -1.6 +/- 5.1 ml/min/1.73 m(2); p = 0.03). Amongst 173 patients with moderate renal impairment (mGFR 30-59 ml/min/1.73 m(2)), renal function improvement was also greater amongst everolimus patients than in controls (Delta mGFR 5.1 +/- 11.1 vs -0.5 +/- 8.7 ml/min/1.73 m(2); p andlt; 0.01). In 55 patients with mGFR 60 to 89 ml/min/1.73 m(2), mGFR did not change significantly in either group. Improvement in mGFR was limited to patients with a median time since TTx of less than 4.6 years and was also influenced by CM reduction during the study period. less thanbrgreater than less thanbrgreater thanCONCLUSIONS: Everolimus introduction and reduced CNI significantly improved renal function amongst maintenance TTx patients with pre-existing advanced renal failure. This beneficial effect was limited to patients undergoing conversion in less than 5 years after TTx, indicating a window of opportunity that is appropriate for pharmacologic intervention with everolimus.
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  • Barklin, Anne, et al. (author)
  • Alteration of Neuropeptides in the Lung Tissue Correlates Brain Death-Induced Neurogenic Edema
  • 2009
  • In: JOURNAL OF HEART AND LUNG TRANSPLANTATION. - : Elsevier BV. - 1053-2498 .- 1557-3117. ; 28:7, s. 725-732
  • Journal article (peer-reviewed)abstract
    • Background: increased intracranial pressure induces neurogenic pulmonary edema (NPE), potentially explaining why only lungs from less than 20% of brain dead organ donors can be used for transplantation. This study investigated the underlying mechanisms of NPE, focusing on neuropeptides, which potently induce vasoconstriction, vasodilatation, and neurogenic inflammation. Methods: Brain death was induced in 10 pigs by increasing the intracranial pressure. Eight additional pigs served as controls. Neuropeptide Y (NPY), calcitonin gene-related peptide (CGRP), and substance P were analyzed in plasma, bronchoalveolar lavage (BAL) fluid, and homogenized lung tissue 6 hours after brain death. Pulmonary oxygen exchange was estimated using partial pressure of arterial oxygen (Pao(2))/fraction of inspired oxygen (FIO2), and pulmonary edema by wet/dry weight ratio. Results: Brain death induced a decrease in PaO2/FIO2 (P less than 0.001) and increased the wet/dry weight of both apical (p = 0.01) and basal lobes (p = 0.03). NPY and CGRP concentrations were higher in the BAL fluid of brain-dead animals compared with controls (p = 0.02 and p = 0.02) and were positively correlated with the wet/dry weight ratio. NPY content in lung tissue was lower in brain-dead animals compared with controls (p = 0.04) and was negatively correlated with the wet/dry weight ratio. There were no differences in substance P concentrations between the groups. Conclusion: NPY was released from the lung tissue of brain-dead pigs, and its concentration was related to the extent of pulmonary edema. NPY may be one of several crucial mediators of neurogenic pulmonary edema, raising the possibility of treatment with NPY-antagonists to increase the number of available lung donors.
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  • Bergenfeldt, Henrik, et al. (author)
  • Outcomes after ABO-incompatible heart transplantation in adults: A registry study.
  • 2015
  • In: The Journal of Heart and Lung Transplantation. - : Elsevier BV. - 1557-3117 .- 1053-2498. ; 34:7, s. 892-898
  • Journal article (peer-reviewed)abstract
    • In the past, ABO incompatibility was considered an absolute contraindication to heart transplantation (HT) in adults. Advances in ABO-incompatible HT in pediatric patients and ABO-incompatible abdominal transplantation in adult patients have led to clinical exploration of intentional ABO-incompatible HT in adults. However, it is not well known how outcomes in ABO-incompatible adult heart transplant recipients compare with outcomes in ABO-compatible recipients.
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  • Bergenfeldt, Henrik, et al. (author)
  • Time-dependent prognostic effects of recipient and donor age in adult heart transplantation
  • 2019
  • In: Journal of Heart and Lung Transplantation. - : Elsevier BV. - 1053-2498. ; 38:2, s. 174-183
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Recipient age and donor age are well-known prognostic factors in adult heart transplantation. However, the association between donor age and recipient age and their interaction and short- and long-term mortality is unknown. METHODS: We studied 64,354 heart transplants to adult recipients between 1988 and 2013 in the ISHLT Registry. Donor age and recipient age were analyzed as continuous and categorical variables and restricted cubic spline functions to assess non-linear associations and interactions. The end-point was all-cause mortality. RESULTS: In the multivariable analysis, the odds ratio for 30-day mortality per 10-year increase in recipient age was 1.05 (95% confidence interval [CI] 1.01 to 1.08, p = 0.009) compared with 1.19 (95% CI 1.15 to 1.22, p < 0.001) for donor age. In the first year, the hazard ratio for mortality was 1.05 (95% CI 1.02 to 1.07, p < 0.001) for a 10-year increase in recipient age and 1.16 (1.14 to 1.18, p < 0.001) for donor age. In Years 1 to 3, 3 to 5, and 5 to 10 post-transplant, the hazard ratio was 0.89 (95% CI 0.86 to 0.92, p < 0.001), 0.98 (95% CI 0.94 to 1.02, p = 0.266), and 1.14 (95% CI 1.11 to 1.17, p < 0.001) for recipient age, and 1.12 (95% CI 1.08 to 1.14, p < 0.001), 1.07 (95% CI 1.03 to 1.10, p < 0.001), and 1.07 (95% CI 1.05 to 1.10, p < 0.001) for donor age, respectively. There was no interaction of recipient age and donor age with survival at any follow-up time-point. CONCLUSIONS: At 30 days, both higher donor age and recipient age were associated with higher mortality. At 1 to 10 years, older donor age was associated with higher mortality at all follow-up time-points, but the hazard was greater in the short term, and recipient age was associated only with longer term mortality. The risk from donor age appears equal across recipient age groups.
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  • Bobbio, Emanuele, et al. (author)
  • Clinical Diagnosis and Subtyping of Cardiac Amyloidosis by Mass Spectrometry.
  • 2020
  • In: The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation. - : Elsevier BV. - 1557-3117. ; 39:4S
  • Journal article (peer-reviewed)abstract
    • Medical treatment for cardiac amyloidosis (CA) is evolving rapidly. Heart transplantation can be a valid option when followed by transplantation of bone marrow or liver, dependent on the type and origin of the amyloid protein. Thus, accurate typing of amyloidosis has implications for treatment, prognosis, and genetic counseling. Although non-invasive diagnostic techniques can type CA, endomyocardial biopsy (EMB) may be needed in the case of equivocal imaging findings or discordant data. We aimed to define the role of mass spectrometry (MS) for diagnosis and subtyping of CA.Nineteen previously diagnosed CA cases, who underwent EMB at Sahlgrenska University Hospital (SU), Gothenburg, between the beginning 1990s and 2016, were selected. MS analysis, modified from was conducted on duplicate samples from myocardial tissue for each case included.1 Clinical features and diagnoses were used as gold standard and compared to the MS findings.Clinical diagnosis and the MS analysis agreed in 14 cases (73.7 %); in 3/19 (15.8 %) diagnosis was unclear or discordant (Fig.1). MS analysis revealed that transthyretin (TTR) amyloidosis was the most abundant amyloid protein in the samples examined (9/19; 47.3 %), whereas the AA subtype only occurred in 1 case (5.2 %). The AL κ type amyloidosis occurred in 3 cases (15.8 %), and AL λ type in six cases (31.6 %). These results strongly correlated with the clinical features in all patients. Clinical diagnosis could not be retrieved from the medical records in 2 cases (10.4 %). Additional 20 patients with clinical CA are presently under study.MS analysis of a small amount of endomyocardial tissue can be used to subtype CA with a high diagnostic validity. The method differentiated between TTR, SAA and Ig light chain amyloidosis. AL κ and AL λ identities correlated to those found in serum and urine electrophoreses. MS can therefore be of use to subtype CA for cases in which clinical findings are inconclusive. 1) Brambilla F et al. Blood. 2012 Feb 23;119(8):1844-7.
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  • Bolys, Ramunas, et al. (author)
  • Vascular function in the cadaver up to six hours after cardiac arrest
  • 1999
  • In: The Journal of Heart and Lung Transplantation. - 1557-3117. ; 18:6, s. 582-586
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: The aim of the study was to evaluate how well vascular function is retained in a cadaver kept in a room with a temperature of 21 degrees C. METHODS: The aorta and pulmonary artery of rats were investigated in organ baths as fresh controls and after 1, 2, 3, or 6 hours' storage in the cadaver. Six-hour-old cadaver aortas were transplanted and investigated after 24 hours and 60 days. RESULTS: After 3 hours' storage there was no significant decrease in smooth muscle contractile function in either aorta or pulmonary artery. After 6 hours' storage both the aorta and the pulmonary artery demonstrated a significant decrease in smooth muscle contractile function, 30% (p < 0.05) and 44% (p < 0.001), respectively, compared to fresh controls. Storing the aorta for 2 hours and the pulmonary artery for 6 hours caused no significant decrease in endothelium-dependent relaxing function. In aorta segments investigated after 3 and 6 hours there was a significant decrease in endothelium-dependent relaxation, 12% (p < 0.05) and 29% (p < 0.001), respectively. Six-hour-old cadaver aortas transplanted and investigated after 24 hours or 60 days demonstrated no significant changes in endothelium-dependent relaxation and smooth muscle function compared to fresh controls. CONCLUSION: The pulmonary artery can tolerate 3 hours of warm ischemia in the nonheart-beating cadaver without loss of endothelium-dependent relaxation and smooth muscle function. The dysfunction seen in 6-hour-old cadaver aortas was normalized after transplantation and 24 hours of reperfusion.
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  • Brenner, P., et al. (author)
  • Worldwide First Successful and Reproducable Long-Term Survival up to Half a Year : Completed Preclinical Study with Life-Supporting Orthotopic Pig-to-Baboon Cardiac Xenotransplantation (oXHTx) Fullfilling the ISHLT Prerequisite for Clinical Cardiac Xenotransplantation
  • 2020
  • In: The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation. - : Elsevier BV. - 1557-3117. ; 39:4, s. 12-12
  • Conference paper (peer-reviewed)abstract
    • PURPOSE: Major hurdles in oXHTx are the delayed xenograft rejection, the early perioperative cardiac xenograft dysfunction (PCXD) and the pig heart overgrowth, which were solved in this study with a costimulation blockade, a new non-ischemic cold preservation and a growth inhibition by anti-proliferative drugs. Aim was to achieve a 90-days-survival of minimal 60% (6 of 10 baboons) in this life-supporting orthotopic pig-to-baboon model (oXHTx), because this is the recommendation of the ISHLT to begin a clinical cardiac XT program. METHODS: We transplanted 8 GalKO/hCD46/hTM transgenic (tg) pig hearts orthotopically into baboons with using a basic immunosuppression consisting of ATG, rituximab, mycophenolate (MMF), cortisone and a costimulation blockade CD40mAb (high dose: 50 mg/kg). To prevent PCXD, we used instead of the crystalloid solution a new non-ischemic 8°C cold perfusion technique with oxygenated erythrocytes. Additional antihypertensive drugs and an mTOR inhibitor (temsirolimus) were applied to inhibit pig xenograft growth and hypertrophy. RESULTS: In comparison to our previous group with crystalloid cardioplegia (Längin et al. Nature. 2018;564:430-433) in this group with cold perfusion preservation (non-ischemic) no PCXD was found. One baboon died of a pancreatitis on day 14, another of sepsis on day 26. By using the antiproliferative therapy, 6 of 8 recipient baboons reached the end of study, were long-term surviving (4 were actively terminated after 90 days according to the guidelines of our government). With special permit two further experiments could be prolonged to half a year and the animals were terminated on day 182 and 195. All baboons lived under excellent physical conditions and no hyperacute rejection or DXR occurred. CONCLUSION: First time in a life-supporting oXHT of multi-tg pig hearts here was a consistent reproduceable long-term survival of 3 - 6 months achieved, which is a major progress after 25 years of research. This is an essential milestone and breakthrough and meets the prerequisite according to the ISHLT to begin a clinical phase I study with patients in terminal heart failure. This paves the way to clinical cardiac XT in the next 2 to 5 years.
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  • Dalvindt, M., et al. (author)
  • Chronic Pain One to Five Years after Heart Transplantation
  • 2020
  • In: The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation. - : Elsevier BV. - 1557-3117. ; 39:4, s. 498-498
  • Conference paper (peer-reviewed)abstract
    • PURPOSE: We know that pain has far-reaching detrimental effects across various life-domains and also affects health related quality of life after solid organ transplantation. However, the extent to which heart recipients experience chronic bodily pain in the years after heart transplantation is a neglected field. Pain is reported to be a major problem after other types of solid organ transplantation. Neither the prevalence nor consequences of chronic pain after heart transplantation have been fully explored or understood. Therefore, the aim was to present a multidimensional assessment of self-reported pain one to five years after heart transplantation and its relationship with transplant specific well-being. METHODS: This nationwide, cross-sectional cohort study is part of the Self-management after thoracic transplantation study. A total of 79 heart recipients, who were due for their annual follow-up at one (n=28), two (n=17), three (n=11), four (n=17) and five years (n=5) after heart transplantation were included. We used three instruments; the Pain-O-Meter (POM), which provides information about pain intensity, sensation, location and duration and the Organ Transplant Symptom and Wellbeing Instrument (OTSWI) and the Psychological General Wellbeing Instrument. RESULTS: The overall prevalence of pain was 57% after 1 year, 76 % after 2 years, 73 % after 3 years, 35 % after 4 years and 50 % after 5 years. Women experienced higher pain intensity than men. The three most common pain locations were feet, back and legs. Heart recipients with pain reported lower transplant specific and psychological well-being as well as higher symptom distress from other symptoms than pain. Those who was back to work reported less pain than those not working. Heart recipients with high general fatigue reported more pain than those less fatigued and there was a relationship between general fatigue, physical fatigue, reduced activity and total pain intensity score. The more fatigue the more pain. CONCLUSION: Chronic bodily pain up to 5 years after heart transplantation reduces perceived well-being. Heart recipients with pain report higher symptom distress than those without pain. Screening for pain, especially among female heart recipients should be mandatory.
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  • Denfeld, Quin E., et al. (author)
  • Assessing and managing frailty in advanced heart failure: An International Society for Heart and Lung Transplantation consensus statement
  • 2024
  • In: The Journal of Heart and Lung Transplantation. - : Elsevier. - 1053-2498 .- 1557-3117. ; 43:1
  • Journal article (peer-reviewed)abstract
    • Frailty is increasingly recognized as a salient condition in patients with heart failure (HF) as previous studies have determined that frailty is highly prevalent and prognostically significant, particularly in those with advanced HF. Definitions of frailty have included a variety of domains, including physical performance, sarcopenia, disability, comorbidity, and cognitive and psychological impairments, many of which are common in advanced HF. Multiple groups have recently recommended incorporating frailty assessments into clinical practice and research studies, indicating the need to standardize the definition and measurement of frailty in advanced HF. Therefore, the purpose of this consensus statement is to provide an integrated perspective on the definition of frailty in advanced HF and to generate a consensus on how to assess and manage frailty. We convened a group of HF clinicians and researchers who have expertise in frailty and related geriatric conditions in HF, and we focused on the patient with advanced HF. Herein, we provide an overview of frailty and how it has been applied in advanced HF (including potential mechanisms), present a definition of frailty, generate suggested assessments of frailty, provide guidance to differentiate frailty and related terms, and describe the assessment and management in advanced HF, including with surgical and nonsurgical interventions. We conclude by outlining critical evidence gaps, areas for future research, and clinical implementation. J Heart Lung Transplant 2024;43:1-27 (c) 2023 International Society for Heart and Lung Transplantation. All rights reserved.
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  • Esmaily, Sorosh, et al. (author)
  • Patient Outcomes after Heart Transplantation in Sweden between 1988 and 2017: Continuous Improvement in Survival.
  • 2020
  • In: The Journal of heart and lung transplantation. 39 (4), S284. - : Elsevier BV. - 1557-3117 .- 1053-2498.
  • Conference paper (peer-reviewed)abstract
    • To investigate the survival of heart transplant (HTx) recipients during different time periods in Sweden. We hypothesized that the survival for HTx recipients has improved following advancements in the management of these patients.Data was obtained through the database of the organ exchange organization Scandiatransplant. All patients who underwent HTx in Sweden between Jan 1988 and Dec 2017 were included. Patients were divided into five cohorts of six-year periods each.A total of 1137 HTx recipients were included. Main causes of transplantation were dilated cardiomyopathy (44 %) and ischemic heart disease (18 %). Retransplantation constituted a small portion of the overall total (2 %). The cohorts were similar in terms of age and gender, while later cohorts had higher BMI, lower GFR and longer ischemia time (Tab. 1). The later cohorts received organs from older donors (Tab. 1). The amount of heart transplantations performed in Sweden has increased with time (Tab. 1). Log-rank test comparing the survival curves was able to show improved survival during later eras (Fig. 1).Survival among HTx recipients has significantly improved in Sweden over time, despite less favorable recipients and donor characteristics. This was related to both reduced postoperative mortality and also improved long-time survival.
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