OBJECTIVES In the third report of the European Registry for Patients with Mechanical Circulatory Support of the European Association for Cardio-Thoracic Surgery, outcomes of patients receiving mechanical circulatory support are reviewed... more
OBJECTIVES In the third report of the European Registry for Patients with Mechanical Circulatory Support of the European Association for Cardio-Thoracic Surgery, outcomes of patients receiving mechanical circulatory support are reviewed in relation to implant era. METHODS Procedures in adult patients (January 2011-June 2020) were included. Patients from centres with <60% follow-ups completed were excluded. Outcomes were stratified into 3 eras (2011-2013, 2014-2017 and 2018-2020). Adverse event rates (AERs) were calculated and stratified into early phase (<3 months) and late phase (>3 months). Risk factors for death were explored using univariable Cox regression with a stepwise time-varying hazard ratio (<3 vs >3 months). RESULTS In total, 4834 procedures in 4486 individual patients (72 hospitals) were included, with a median follow-up of 1.1 (interquartile range: 0.3-2.6) years. The annual number of implants (range: 346-600) did not significantly change (P = 0.41). Bo...
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Chronic Toxoplasma gondii (T. gondii ) infection is known to trigger potentially adverse immuno-regulatory changes, but the long-term implication for heart transplant (HTx) recipients has not been assessed previously. Hence, we evaluated... more
Chronic Toxoplasma gondii (T. gondii ) infection is known to trigger potentially adverse immuno-regulatory changes, but the long-term implication for heart transplant (HTx) recipients has not been assessed previously. Hence, we evaluated the risk of mortality, development of cardiac allograft vasculopathy (CAV) and acute cellular rejection amongst T. gondii seropositive HTx recipients and the four donor/recipient seropairing groups. Methods: Frozen pre-HTx serum samples of 288 recipients and 246 donors were evaluated for T. gondii serostatus using Platelia IgG immunoassay method. All patients had also undergone prospective serostatus evaluation using alternative assays and results determined by the two methods were compared. Follow-up data regarding mortality, CAV development and acute cellular rejection was available for all patients. Results: Overall, 211 (73%) recipients were seronegative and 77 (27%) were seropositive. In total, 82 recipients died, 76 developed CAV and 82 had si...
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The motivation for research on animals as a source of cells, tissues and organs for human transplantation (xenotransplantation) is the scarcity of suitable donors for patients with end-stage organ failure. Use of animals in both... more
The motivation for research on animals as a source of cells, tissues and organs for human transplantation (xenotransplantation) is the scarcity of suitable donors for patients with end-stage organ failure. Use of animals in both experimental and clinical settings raise considerable ethical concerns, especially when non-human primates are used. The pig may represent an acceptable source animal for xenotransplantation and is today regarded as the animal of choice. Xenotransplantation seems defensible from an ethical perspective, but should not be performed in humans until preclinical animal-to-animal xenotransplantations have a predictable rate of success and the risk to society at large is negligible. For the individual patient and his or her next of kin involved, issues of autonomy and proper consent procedures must be given high priority. Safeguards must be established, for the patient and for society at large, in relation to health hazards from infectious organisms, particularly r...
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OBJECTIVES Targeted temperature management (32-36°C) is used for neuroprotection in cardiac arrest survivors. The isolated effects of hypothermia on myocardial function, as used in clinical practice, remain unclear. Based on experimental... more
OBJECTIVES Targeted temperature management (32-36°C) is used for neuroprotection in cardiac arrest survivors. The isolated effects of hypothermia on myocardial function, as used in clinical practice, remain unclear. Based on experimental results, we hypothesized that hypothermia would reversibly impair diastolic function with less tolerance to increased heart rate in patients with uninsulted hearts. DESIGN Prospective clinical study, from June 2015 to May 2018. SETTING Cardiothoracic surgery operation room, Oslo University Hospital. PATIENTS Twenty patients with left ventricular ejection fraction greater than 55%, undergoing ascending aorta graft-replacement connected to cardiopulmonary bypass were included. INTERVENTIONS Left ventricular function was assessed during reduced cardiopulmonary bypass support at 36°C, 32°C prior to graft-replacement, and at 36°C postsurgery. Electrocardiogram, hemodynamic, and echocardiographic recordings were made at spontaneous heart rate and 90 beats per minute at comparable loading conditions. MEASUREMENTS AND MAIN RESULTS Hypothermia decreased spontaneous heart rate, and R-R interval was prolonged (862 ± 170 to 1,156 ± 254 ms, p < 0.001). Although systolic and diastolic fractions of R-R interval were preserved (0.43 ± 0.07 and 0.57 ± 0.07), isovolumic relaxation time increased and diastolic filling time was shortened. Filling pattern changed from early to late filling. Systolic function was preserved with unchanged myocardial strain and stroke volume index, but cardiac index was reduced with maintained mixed venous oxygen saturation. At increased heart rate, systolic fraction exceeded diastolic fraction (0.53 ± 0.05 and 0.47 ± 0.05) with diastolic impairment. Strain and stroke volume index were reduced, the latter to 65% of stroke volume index at spontaneous heart rate. Cardiac index decreased, but mixed venous oxygen saturation was maintained. After rewarming, myocardial function was restored. CONCLUSIONS In patients with normal left ventricular function, hypothermia impaired diastolic function. At increased heart rate, systolic function was subsequently reduced due to impeded filling. Changes in left ventricular function were rapidly reversed after rewarming.
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Methods: Osteodifferentiation was induced in 10 VIC cultures isolated from healthy and calcified human aortic valves by addition of osteogenic medium for 10 days. Proteins were isolated from differentiated VIC, and as well from... more
Methods: Osteodifferentiation was induced in 10 VIC cultures isolated from healthy and calcified human aortic valves by addition of osteogenic medium for 10 days. Proteins were isolated from differentiated VIC, and as well from undifferentiated VIC cultures from same donors and proteomics analysis was performed (Q Exactive instrument, DDA mode, 0.1% formic acid (A)/0.1% formic acid/acetonitrile (B) gradient). LFQ data analysis using PEAKS studio X and DAVID analysis were applied.
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Introduction: To extend the number of available organs for lung transplantation (LTx), donors with a smoking history are increasingly accepted. Previous studies show conflicting results as to whether this impairs recipient survival. Aims... more
Introduction: To extend the number of available organs for lung transplantation (LTx), donors with a smoking history are increasingly accepted. Previous studies show conflicting results as to whether this impairs recipient survival. Aims and objectives: The aim was to assess the effects of using lungs from donors with a smoking history for LTx for recipients with cystic fibrosis (CF). Methods: All recipients of bilateral LTx in Norway and Denmark 1990-2013 were included. Donor information and data about recipient survival and lung function was extracted from existing registries. Results: While there was no negative effect of donor smoking status when including all LTx recipients (n=388), we found a negative association between donor smoking status and post-LTx survival in the CF patients (n=86), in whom one-year survival was 82 % vs 90 % and five year survival was 49 % vs 73 % comparing smoking to non-smoking donors (Log-rank p-value 0.005). The negative effects of using organs from smoking donors remained significant when adjusting for donor and recipient age and sex, organ ischemia time and transplant center location in multivariate cox regression analysis. Conclusion: Using donors with a positive smoking history in double lung transplant recipients with cystic fibrosis is associated with inferior survival and decreased lung function.
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Throughout the world, the scarcity of donor organs makes optimal allocation systems necessary. In the Scandiatransplant countries, organs for lung transplantation are allocated nationally. To ensure shorter wait time for critically ill... more
Throughout the world, the scarcity of donor organs makes optimal allocation systems necessary. In the Scandiatransplant countries, organs for lung transplantation are allocated nationally. To ensure shorter wait time for critically ill patients, the Scandiatransplant urgent lung allocation system (ScULAS) was introduced in 2009, giving supranational priority to patients considered urgent. There were no pre-defined criteria for listing a patient as urgent, but each center was granted only 3 urgent calls per year. This study aims to explore the characteristics and outcome of patients listed as urgent, assess changes associated with the implementation of ScULAS, and describe how the system was utilized by the member centers. All patients listed for lung transplantation at the 5 Scandiatransplant centers 5years before and after implementation of ScULAS were included. After implementation, 8.3% of all listed patients received urgent status, of whom 81% were transplanted within 4 weeks. P...
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Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are increasingly being used for modeling heart disease and are under development for regeneration of the injured heart. However, incomplete structural and functional... more
Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are increasingly being used for modeling heart disease and are under development for regeneration of the injured heart. However, incomplete structural and functional maturation of hiPSC-CM, including lack of T-tubules, immature excitation-contraction coupling, and inefficient Ca-induced Ca release remain major limitations. Thyroid and glucocorticoid hormones are critical for heart maturation. We hypothesized that their addition to standard protocols would promote T-tubule development and mature excitation-contraction coupling of hiPSC-CM when cultured on extracellular matrix with physiological stiffness (Matrigel mattress). hiPSC-CM were generated using a standard chemical differentiation method supplemented with T3 (triiodothyronine) and/or Dex (dexamethasone) during days 16 to 30 followed by single-cell culture for 5 days on Matrigel mattress. hiPSC-CM treated with T3+Dex, but not with either T3 or Dex alone, de...
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In dilated cardiomyopathy (DCM), adverse myocardial remodeling is essential, potentially involving Notch signaling. We hypothesized that secreted Notch ligands would be dysregulated in DCM. We measured plasma levels of the canonical... more
In dilated cardiomyopathy (DCM), adverse myocardial remodeling is essential, potentially involving Notch signaling. We hypothesized that secreted Notch ligands would be dysregulated in DCM. We measured plasma levels of the canonical Delta-like Notch ligand 1 (DLL1) and non-canonical Notch ligands Delta-like 1 homologue (DLK1) and periostin (POSN) in 102 DCM patients and 32 matched controls. Myocardial mRNA and protein levels of DLL1, DLK1, and POSN were measured in 25 explanted hearts. Our main findings were: (i) Circulating levels of DLL1 and POSN were higher in patients with severe DCM and correlated with the degree of diastolic dysfunction and (ii) right ventricular tissue expressions of DLL1, DLK1, and POSN were oppositely associated with cardiac function indices, as high DLL1 and DLK1 expression corresponded to more preserved and high POSN expression to more deteriorated cardiac function. DLL1, DLK1, and POSN are dysregulated in end-stage DCM, possibly mediating different effects on cardiac function.
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We aimed to study the cardiac expression of bone morphogenetic protein 2, its receptor 1 b, and connective tissue growth factor, factors implicated in cardiac embryogenesis, following ischemia/hypoxia, heart failure, and in remodeling... more
We aimed to study the cardiac expression of bone morphogenetic protein 2, its receptor 1 b, and connective tissue growth factor, factors implicated in cardiac embryogenesis, following ischemia/hypoxia, heart failure, and in remodeling hearts from humans and mice. Biopsies from the left ventricle of patients with end-stage heart failure due to dilated cardiomyopathy or coronary artery disease were compared with donor hearts and biopsies from patients with normal heart function undergoing coronary artery bypass grafting. Mouse model of post-infarction remodeling was made by permanent ligation of the left coronary artery. Hearts were analyzed by real-time polymerase chain reaction and Western blotting after 24 hours and after 2 and 4 weeks. Patients with dilated cardiomyopathy and mice post-infarction had increased cardiac expression of connective tissue growth factor. Bone morphogenetic protein 2 was increased in human hearts failing due to coronary artery disease and in mice post-inf...
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Myocardial infarction (MI) triggers a reparative response involving fibroblast proliferation and differentiation driving extracellular matrix modulation necessary to form a stabilizing scar. Recently, it was shown that a genetic variant... more
Myocardial infarction (MI) triggers a reparative response involving fibroblast proliferation and differentiation driving extracellular matrix modulation necessary to form a stabilizing scar. Recently, it was shown that a genetic variant of the base excision repair enzyme NEIL3 was associated with increased risk of MI in humans. Here, we report elevated myocardial NEIL3 expression in heart failure patients and marked myocardial upregulation of Neil3 after MI in mice, especially in a fibroblast-enriched cell fraction. Neil3(-/-) mice show increased mortality after MI caused by myocardial rupture. Genome-wide analysis of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) reveals changes in the cardiac epigenome, including in genes related to the post-MI transcriptional response. Differentially methylated genes are enriched in pathways related to proliferation and myofibroblast differentiation. Accordingly, Neil3(-/-) ruptured hearts show increased proliferation of fibroblasts an...
Research Interests: Biology, Survival Analysis, DNA damage, Medicine, Heart Failure, and 15 moreHumans, Collagen, DNA methylation, Phenotype, Myofibroblasts, Myocardial Infarction, Myocardium, Time Factors, Cell Proliferation, Leukocytes, Gene Expression Regulation, Gene expression profiling, Matrix Metalloproteinase, fibroblasts, and Connective Tissue Diseases
Ventricular blood stasis is a concern for continuous flow mechanical support devices and might contribute to the formation of thromboembolic events. The HeartWare® Ventricular Assist System (HVAD®) is equipped with the Lavare™ cycle that... more
Ventricular blood stasis is a concern for continuous flow mechanical support devices and might contribute to the formation of thromboembolic events. The HeartWare® Ventricular Assist System (HVAD®) is equipped with the Lavare™ cycle that is a periodic speed modulation feature designed to alter flow patterns within the left ventricle and reduce areas of potential blood stasis. Here, we report in vitro and clinical findings on the effects of the Lavare cycle. The effect of pump speed changes on the intraventricular flow field was examined with an in vitro particle image velocimetry model. The clinical impact of the Lavare cycle was evaluated through a retrospective review of the ReVOLVE study which includes 248 patients implanted with the HVAD following Conformité Européenne Mark in nine centres in Europe and Australia. Baseline characteristics, adverse event profiles and Kaplan-Meier survival estimates were stratified by patients using/not using the Lavare cycle. Particle image veloc...
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Research Interests: Nonparametric Statistics, Biomarkers, Survival Analysis, Mitochondria, Medicine, and 14 moreHeart Failure, Humans, Female, Male, Clinical Sciences, Aged, Middle Aged, Prognosis, Reference Values, Cardiac failure, Predictive value of tests, Case Control Studies, Severity of Illness Index, and Cardiovascular medicine and haematology
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Chronic Toxoplasma gondii (T. gondii ) infection is known to trigger potentially adverse immuno-regulatory changes, but the long-term implication for heart transplant (HTx) recipients has not been assessed previously. Hence, we evaluated... more
Chronic Toxoplasma gondii (T. gondii ) infection is known to trigger potentially adverse immuno-regulatory changes, but the long-term implication for heart transplant (HTx) recipients has not been assessed previously. Hence, we evaluated the risk of mortality, development of cardiac allograft vasculopathy (CAV) and acute cellular rejection amongst T. gondii seropositive HTx recipients and the four donor/recipient seropairing groups. Methods: Frozen pre-HTx serum samples of 288 recipients and 246 donors were evaluated for T. gondii serostatus using Platelia IgG immunoassay method. All patients had also undergone prospective serostatus evaluation using alternative assays and results determined by the two methods were compared. Follow-up data regarding mortality, CAV development and acute cellular rejection was available for all patients. Results: Overall, 211 (73%) recipients were seronegative and 77 (27%) were seropositive. In total, 82 recipients died, 76 developed CAV and 82 had significant cellular rejection. Recipient seropositivity was associated with a significantly higher risk of all-cause mortality (hazard ratio [HR], 1.9; 95% CI, 1.1–3.4; p= 0.02) and CAV mortality (HR=4.4; 95% CI, 1.3–15.6, p=0.02), but was not associated with earlier CAV development or higher rejection score. Donor/recipient seropairing status was not a risk factor for any endpoint. Conclusions: T. gondii seropositivity amongst HTx recipients is associated with a significantly increased risk of long-term total, and in particular CAV-related, mortality. This may be mediated via immunoregulatory changes triggered by chronic T. gondii infection and needs to be explored further.
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Research Interests: Medicine and Circulation
The use of mammalian target of rapamycin (mTOR) inhibitors have been limited by adverse events (AE), including delayed wound healing. We retrospectively reviewed all AE and serious AE (SAE) in The Scandinavian heart transplant (HTx)... more
The use of mammalian target of rapamycin (mTOR) inhibitors have been limited by adverse events (AE), including delayed wound healing. We retrospectively reviewed all AE and serious AE (SAE) in The Scandinavian heart transplant (HTx) everolimus (EVE) de novo trial with early calcineurin (CNI) avoidance (SCHEDULE). The aim of the study was to compare wound complications between EVE and CNI based regimen. A total of 115 patients (mean age 51±13years, 73% men) were randomized within five days post-HTx to low dose EVE and reduced dose Cyclosporine (CyA) followed by early CyA withdrawal (EVE group; n=56) or standard CyA regimen (CyA group; n=59). All AE/SAEs were prospectively recorded according to the SCHEDULE study protocol, and re-assessed retrospectively by two independent reviewers. Wound complication as primary endpoint was defined as any complication associated with failure of tissue healing. Secondary endpoint was total number of events involving surgical intervention. There were ...
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Introduction: One option to increase the number of organs for lung transplantation (LuTx) is to use lungs from older donors, and recipient survival disadvantage for donors >55 years has not been shown. This study aims to elucidate the... more
Introduction: One option to increase the number of organs for lung transplantation (LuTx) is to use lungs from older donors, and recipient survival disadvantage for donors >55 years has not been shown. This study aims to elucidate the effects of donor age on recipient lung function, chronic lung allograft dysfunction (CLAD) and survival. Methods: Donor age and recipient data for all double lung transplantations (DLTx) in Norway between 1990 and 2013 were assessed. Results: Data were available for 303 out of 306 DLTx. Mean donor age was 41.9 years (SD: 15.3, Range: 9-69). There was a sig. correlation between donor and recipient age (r=.27, p 55 years to younger donors. However, we found an inverse correlation between donor age and lung function (FEV1%, DLCO%, 6MWT) at 2 years post LuTx, and comparing CLAD vs. non-CLAD, donor age was sig. higher in recipients with CLAD at 2-year (50 vs 40, p=0.01) follow-up while recipient age was similar. The survival was lower in recipients with organs from donors aged 40-54 years (figure 1) compared to both older and younger donors. Conclusion: Recipient lung function at two years post LuTx inversely correlated with donor age, and recipients with donors aged 40-54 had reduced survival. Whether this was due to donor factors or recipient selection should be determined in larger studies.
BACKGROUND High intensity interval training (HIIT) is an efficient form of exercise training in patients with coronary heart disease and heart failure, while heart transplant (HTx) recipients, main...
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Chronic thromboembolic pulmonary hypertension (CTEPH) induces right ventricular (RV) adaptive changes but often results in RV failure and death. Balloon pulmonary angioplasty (BPA) is a treatment option in patients in whom pulmonary... more
Chronic thromboembolic pulmonary hypertension (CTEPH) induces right ventricular (RV) adaptive changes but often results in RV failure and death. Balloon pulmonary angioplasty (BPA) is a treatment option in patients in whom pulmonary endarterectomy is contraindicated and in patients with residual pulmonary hypertension after pulmonary endarterectomy. We hypothesized that RV reverse remodeling and improved RV function would occur after BPA in patients with CTEPH. In 26 patients with CTEPH (59 ± 12 years old; 11 men), echocardiography, cardiopulmonary exercise testing, blood samples, and right-sided cardiac catheterization were performed before and after 4 ± 2 BPA procedures. Echocardiography images were analyzed off-line with particular focus on RV function according to current recommendations. Differences from baseline to follow-up were analyzed by paired samples t tests. Significant improvements in hemodynamics, peak oxygen consumption, and levels of N-terminal pro-B-type natriuretic peptide were detected after BPA. All measures of RV function improved considerably, including fractional area change (+6%; p = 0.003), tricuspid annular plane systolic excursion (+3 mm; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), and RV free wall peak strain (-4.4; p = 0.002). RV end-diastolic diameter, area, and free wall thickness decreased significantly, whereas left ventricular diameter and stroke volume increased. After BPA, a significant improvement in RV functional parameters could be observed by echocardiography, adding credibility to this form of treatment in patients with CTEPH.
Research Interests: Forecasting, Treatment Outcome, Medicine, Pulmonary Hypertension, Echocardiography, and 11 moreHumans, Female, Pulmonary Embolism, Male, Follow-up studies, Cardiac Catheterization, Middle Aged, Retrospective Studies, Ventricular Remodeling, Recovery of Function, and Cardiovascular medicine and haematology
... 561 Persisting anaemia one year after heart transplantation is not associated with an adverse long-term prognosis S. Arora, AK Andreassen, E. Gude, S. Simonsen, R. Skaardal, A ... The hemodynamic ef-fects of Levosimendan (Levo) are... more
... 561 Persisting anaemia one year after heart transplantation is not associated with an adverse long-term prognosis S. Arora, AK Andreassen, E. Gude, S. Simonsen, R. Skaardal, A ... The hemodynamic ef-fects of Levosimendan (Levo) are usually maintained during several days. ...
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ABSTRACT
By February 1997, the number of heart transplantations at the National Hospital had reached 265. In our department, the first bridge to transplantation in using Thoratec artificial heart was performed in 1995. A 44 year-old patient with... more
By February 1997, the number of heart transplantations at the National Hospital had reached 265. In our department, the first bridge to transplantation in using Thoratec artificial heart was performed in 1995. A 44 year-old patient with life-threatening heart failure was placed for one week on cardiopulmonary assist with an intra-aortic balloon pump and a veno-arterial cardiopulmonary bypass. Due to unceasing heart failure a Thoratec left ventricular assist device was implanted as a bridge to transplant. The patient was successfully transplanted two days after implantation of Thoratec. After eight months follow-up he is in New York Heart Association (NYHA) functional class I. Another patient, 17 years of age, and with dilated cardiomyopathy, went into cardiogenic shock while awaiting heart transplantation. For three days he had cardiopulmonary assist with intra-aortic balloon pump and venoarterial bypass with an oxygenator. After seven weeks on the left ventricular assist device he ...
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The increasing demand for pulmonary retransplantation (re-LTx) raises ethical issues on the correct allocation of the scarce donor pool. Thus, we performed a thorough review of the current results for re-LTx in the Nordic countries.... more
The increasing demand for pulmonary retransplantation (re-LTx) raises ethical issues on the correct allocation of the scarce donor pool. Thus, we performed a thorough review of the current results for re-LTx in the Nordic countries. Seventy-five patients with a median age of 50 years (range, 22 to 64 years) underwent re-LTx from 1992 until June 2013, of which 53 had single re-LTx, 21 had double re-LTx, and 1 patient underwent a heart-lung retransplantation. Primary graft dysfunction (PGD) was the primary indication in 9 cases, bronchiolitis obliterans syndrome (BOS) in 62 cases, and airway complications in 4 cases. Patients who underwent re-LTx in the period 1992 to 1999 (n = 16) had a 1-year survival of 37.5% (95% confidence interval [CI], 19.9 to 70.6), whereas patients who underwent re-LTx in the period 2000 to 2013 (n = 64) had a 1-year survival of 81.0% (95% CI, 71.5 to 91.8). Corresponding 5-year survival was 25.0% (95% CI, 10.7 to 58.4) in the early era group (1992 to 1999) a...
Research Interests: Treatment Outcome, Medicine, Humans, Female, Male, and 12 moreYoung Adult, Clinical Sciences, Middle Aged, Adult, Survival Rate, Retrospective Studies, Bronchiolitis Obliterans, Reoperation, Lung Transplantation, Patient selection, Cardiovascular medicine and haematology, and Primary graft dysfunction
A 71-year-old woman with severe congestive heart failure and failed mitral valve repair was referred for surgery. Because of her low ejection fraction, a valve-in-ring procedure was suggested. There was a great difference in the given... more
A 71-year-old woman with severe congestive heart failure and failed mitral valve repair was referred for surgery. Because of her low ejection fraction, a valve-in-ring procedure was suggested. There was a great difference in the given size for the 34-mm Carpentier-Edwards-Physio-Ring and the biggest available transcatheter valve of 29 mm from Edwards. Therefore, we did a "bench test." We expanded a 29-mm Edwards SAPIEN-XT aortic valve in a 34-mm Carpentier-Edwards-Physio-Ring. It fitted well and turned out circular with good coaptation of the leaflets. Thereafter, a successful transapical mitral valve-in-ring implantation on cardiopulmonary bypass was performed, and additional leads for cardiac resynchronization was placed.
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Heart transplantation has been a treatment option in Norway for selected patients with terminal congestive heart failure since 1983. The number of transplants is limited by donor availability. Few Norwegian doctors are aware of the... more
Heart transplantation has been a treatment option in Norway for selected patients with terminal congestive heart failure since 1983. The number of transplants is limited by donor availability. Few Norwegian doctors are aware of the challenges to be expected in taking care of heart transplant recipients. In the present paper we therefore present our experience so far. We have followed individuals within our patient cohort for up to 22 years. The cohort consists of 522 patients (mean age 48.8 years +/- 13.6), somewhat unequally distributed from various parts of the country, reflecting the local referring practice. We have a complete overview of the patients who are partly followed up locally, but come to a control at least once a year at our hospital. Mean survival in these patients is 12 years. With an expected survival of less than one year without transplantation, these are strong results that compare well with international figures. Patients younger than 50 years at transplantatio...
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The motivation for research on animals as a source of cells, tissues and organs for human transplantation (xenotransplantation) is the scarcity of suitable donors for patients with end-stage organ failure. Use of animals in both... more
The motivation for research on animals as a source of cells, tissues and organs for human transplantation (xenotransplantation) is the scarcity of suitable donors for patients with end-stage organ failure. Use of animals in both experimental and clinical settings raise considerable ethical concerns, especially when non-human primates are used. The pig may represent an acceptable source animal for xenotransplantation and is today regarded as the animal of choice. Xenotransplantation seems defensible from an ethical perspective, but should not be performed in humans until preclinical animal-to-animal xenotransplantations have a predictable rate of success and the risk to society at large is negligible. For the individual patient and his or her next of kin involved, issues of autonomy and proper consent procedures must be given high priority. Safeguards must be established, for the patient and for society at large, in relation to health hazards from infectious organisms, particularly r...
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Because of a severe shortage of donor organs, organ transplantation therapy can only be offered to a fraction of all patients needing it. This has sparked an increasing interest in xenotransplantation. Transgenic pigs could potentially... more
Because of a severe shortage of donor organs, organ transplantation therapy can only be offered to a fraction of all patients needing it. This has sparked an increasing interest in xenotransplantation. Transgenic pigs could potentially provide tissue and organs to thousands of patients on waiting lists world-wide. Xenografts may be used as bridges or as permanent alternatives to organ allotransplants. Clinical trials of transplantation of pig cells and tissues to treat diabetes and neurodegenerative disorders are in progress. The most striking immunologic obstacle to xenotransplantation of solid organs, that of hyperacute rejection, is close to being overcome. Next steps in research are to refine immunosuppression, improve our knowledge of physiology and to allow for small and strictly regulated clinical studies. However, the risk for the recipients from infectious agents, particularly retroviruses, and potential dissemination of these in the human population cannot be ignored and m...
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During the five years 1990 through 1994, 70 neonates and infants had surgery for coarctation of the aorta. 30 patients with complex coarctation of the aorta underwent a first stage correction with supplementary ductus ligation and... more
During the five years 1990 through 1994, 70 neonates and infants had surgery for coarctation of the aorta. 30 patients with complex coarctation of the aorta underwent a first stage correction with supplementary ductus ligation and pulmonary artery banding as needed. The mode of surgical repair of coarctation was end-to-end anastomosis in ten patients and patch graft in 20 patient. Mean follow-up was 766 (range 3-1812) days. Mortality after primary procedure was 16.6% (5/30) and after secondary procedure 11.1% (2/18). Three surviving patient developed recoarctation, but only one patients needed re-operation. In spite of improvement in neonatal cardiac surgery, we conclude that a staged approach is still the current treatment in most cases of complex coarctation of the aorta.
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Background. This prospective randomized study compared the inflammatory response in patients undergoing elective on-pump and off-pump coronary artery bypass grafting. Patients and methods. Forty-four patients undergoing elective coronary... more
Background. This prospective randomized study compared the inflammatory response in patients undergoing elective on-pump and off-pump coronary artery bypass grafting. Patients and methods. Forty-four patients undergoing elective coronary artery bypass grafting were recruited with 22 patients randomized to on-pump heart surgery and 22 patients to off-pump coronary bypass surgery. Plasma levels of C3bc, the terminal SC5b-9 complement complex, myeloperoxidase, β -thromboglobulin and prothrombin fragment F1 + 2 were measured before the operation, intraoperatively, at termination of the operation, and two hours post-operatively. Results. Complement was markedly activated in the on-pump group as indicated by a significant increase in C3bc and SC5b-9 (p < 0.001 for both), whereas no complement activation was seen in the off-pump group (p = 0.001 between the groups). In contrast, both groups showed significant activation of neutrophils, platelets and coagulation, as indicated by an early...
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Research Interests:
Background: The biocompatibility of cardiopulmonary bypass surfaces has been improved by heparin and polymer surface modifications. The present study compared the effect of two such coatings on the inflammatory reactions after open heart... more
Background: The biocompatibility of cardiopulmonary bypass surfaces has been improved by heparin and polymer surface modifications. The present study compared the effect of two such coatings on the inflammatory reactions after open heart surgery. Methods:Thirty patients undergoing elective heart surgery were randomly assigned to receive one of two types of coated circuits: Bioline (n=15) or phosphorylcholine (Phisio, n=15). The platelet and leukocyte counts, neutrophil activation (myeloperoxidase), complement activation (C3a and TCC), concentrations of lactate dehydrogenase, 27 cytokines (including interleukins, chemokines and growth factors), thrombin-antithrombin complexes, and the endothelial cell marker syndecan-1 were analyzed at five predetermined time points until 24 hrs post operatively. Results: Most measurements were comparable in both groups. However, myeloperoxidase was significantly higher in the Bioline group (p < 0.001). Postoperative lactate dehydrogenase concentr...
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Objective: Two extracorporeal membrane oxygenation (ECMO) circuits for children under 10 kg were evaluated and compared for plasma leakage, hemolysis, blood transfusions, and durability. Methods: Group A ( n = 20) was supported by ECMO... more
Objective: Two extracorporeal membrane oxygenation (ECMO) circuits for children under 10 kg were evaluated and compared for plasma leakage, hemolysis, blood transfusions, and durability. Methods: Group A ( n = 20) was supported by ECMO circuits with the Minimax oxygenator and the Biomedicus centrifugal pump. Group B ( n = 10) was supported by ECMO circuits with the Lilliput 2 ECMO oxygenator and the Rotaflow centrifugal pump. Results: ECMO circuit durability, as measured by oxygenator lifespan, was significantly better in Group B than in Group A (p = 0.04). There was significantly lower hemolysis, measured by plasma free hemoglobin, in Group B ( p = 0.019), and patients in Group B had significantly less need for antithrombin III transfusion ( p = 0.004). No plasma leakage was observed in Group B oxygenators, but plasma leakage was observed in all Group A oxygenators. Conclusion: The combination of a Rotaflow centrifugal pump and Lilliput 2 ECMO oxygenator in pediatric ECMO circuits ...
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The neonate cardiopulmonary bypass (CPB) circuit, including a KIDS D100 oxygenator (The Sorin Group, Mirandola, Italy) and a D130 arterial filter (The Sorin Group), was evaluated in vitro with respect to the removal of free micro gas... more
The neonate cardiopulmonary bypass (CPB) circuit, including a KIDS D100 oxygenator (The Sorin Group, Mirandola, Italy) and a D130 arterial filter (The Sorin Group), was evaluated in vitro with respect to the removal of free micro gas bubbles. No gas bubbles > 40µm were measured after the arterial filter D130 upon manual introduction of 10 ml of air into the venous line or during the use of vacuum-assisted venous drainage (VAVD). The D130 arterial filter removed 88 % of gas bubbles < 40 µm during manual introduction of air into the venous line; however, only 50 % of gas bubbles < 40 µm were removed during the use of VAVD. The same CPB circuit was evaluated in vivo to compare with another CPB circuit, including a D901 oxygenator (The Sorin Group) and arterial filter D736 (The Sorin Group), in 155 neonates weighing ≤5 kg. The D100 circuit required significantly less priming volume than the D901 circuit. Postoperative haemoglobin was significantly higher, artificial ventilation...
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Complement-activating naturally occurring anti-porcine endothelial cell antibodies (Abs) are responsible for hyperacute rejection in porcine-to-primate transplantation, whereas the role of complement in acute vascular rejection,... more
Complement-activating naturally occurring anti-porcine endothelial cell antibodies (Abs) are responsible for hyperacute rejection in porcine-to-primate transplantation, whereas the role of complement in acute vascular rejection, characterized by type II endothelial cell activation, is less well understood. We previously demonstrated a correlation between porcine type II endothelial cell activation, as detected by E-selectin expression, and human immunoglobulin (Ig)G3 anti-Gal alpha1-3Gal (Gal) Abs, which was not seen for IgG1, IgG2 or IgG4. The present study was undertaken to investigate whether there is a causal relationship between human anti-porcine IgG3 Abs and porcine endothelial cell activation. IgG3 was isolated employing a Protein A column to 98.3% purity. Porcine endothelial cells were incubated with isolated human IgG3 or the combination of IgG1, IgG2 and IgG4. E-selectin expression and complement activation were investigated by flow cytometry and Western blotting, respectively. Purified IgG3, in contrast to the other IgG subclasses, induced a substantial increase in E-selectin expression. This activation was accompanied by complement activation as detected by C3 cleavage, and was abolished by heat inactivation or by adding the complement inhibitor FUT-175. Depletion of anti-Gal Abs reduced E-selectin expression by 60%, consistent with the presence of complement-activating anti-porcine non-Gal Abs of the IgG3 subclass. Collectively, these data strengthen the hypothesis that human anti-porcine endothelial cell Abs of the IgG3 subclass are essential for endothelial cell activation in porcine-to-human species grafts and demonstrate such activation to be partly independent of Gal epitopes.
Research Interests: Complement activation, Flow Cytometry, Complement System, Primates, Xenotransplantation, and 15 moreHumans, Animals, Vascular endothelium, Clinical Sciences, Endothelial cell, Swine, Guanidines, Disaccharides, Graft Rejection, Aorta, Enzyme Linked Immunosorbent Assay, Immunoglobulin, immunoglobulin G, Staphylococcal protein A, and Guinea pigs
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Isolated aortic (AVR, N = 71), mitral (MVR, N = 103), tricuspid (TVR, N = 3), pulmonary (PVR, N = 8), combined AVR + MVR (N = 4), or combined MVR + TVR (N = 2) valve replacement with a Carpentier-Edwards porcine bioprosthesis was... more
Isolated aortic (AVR, N = 71), mitral (MVR, N = 103), tricuspid (TVR, N = 3), pulmonary (PVR, N = 8), combined AVR + MVR (N = 4), or combined MVR + TVR (N = 2) valve replacement with a Carpentier-Edwards porcine bioprosthesis was performed in 191 patients between 1979 and 1986. Mean age was 56.9 +/- 17 (range 5-80) years in the total cohort. The operative mortality rates were 5.6% and 8.7%, respectively, for AVR and MVR. Mean observation time was 8 +/- 4.2 (0-16.7) years (total = 1.467 patient-years). Follow-up was 100% complete with respect to mortality. There were 78 late deaths (44%). Actuarial survival rates at 5 and 10 years were 73.2 +/- 5.2 and 52.1 +/- 6.6 for AVR and 76.7 +/- 4.2 and 61.6 +/- 4.8 for MVR. Coronary artery disease, concomitant coronary artery bypass grafting and emergency operation were significant risk factors of early mortality (p &lt; 0.05). Postoperatively, sepsis and multiorgan failure were associated with early mortality (p &lt; 0.05). The 10-year actuarial freedom from structural deterioration for AVR was 89 +/- 4.6 and 76.4 +/- 4.3 for MVR. It is concluded that structural valve failure is the most important factor that adversely affects the performance of Carpentier-Edwards bioprosthesis.
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ALCAPA, anomalous origin of the left coronary artery from the pulmonary artery is a rare congenital disease. We have from 1990 to 2003 operated on seven patients in our clinic. The objective of this study was to describe our experience of... more
ALCAPA, anomalous origin of the left coronary artery from the pulmonary artery is a rare congenital disease. We have from 1990 to 2003 operated on seven patients in our clinic. The objective of this study was to describe our experience of treating the condition and to remind other doctors of it as a possible diagnosis. The patients were identified by a retrospective review of our clinical records. Symptoms and signs varied from discomfort and pathologic heart murmur to ventricular fibrillation. All patients were operated on by use of cardiopulmonal bypass. Two died postoperatively within one week, two were reoperated later on because of pulmonary artery stenosis. ALCAPA should be suspected if a young patient with no previous history of heart failure presents with dyspnoe, chest pain or dysrhythmia. ALCAPA must be excluded by coronary angiography in younger patients with mitral insufficiency and no other morphological findings. Patients diagnosed early and operated on have a good prognosis.