Marfan syndrome: Evolving organ manifestations-A 10-year follow-up study.

The age-dependent penetrance of organ manifestations in Marfan syndrome (MFS) is not known. The aims of this follow-up study were to explore how clinical features change over a 10-year period in the same Norwegian MFS cohort. In 2003-2004, we investigated 105 adults for all manifestations in the 1996 Ghent nosology. Ten years later, we performed follow-up investigations of the survivors (n = 48) who consented. Forty-six fulfilled the revised Ghent criteria. Median age: females 51 years, range 32-80 years; males 45 years, range 30-67 years. New aortic root dilatation was detected in patients up to 70 years. Ascending aortic pathology was diagnosed in 93 versus 72% at baseline. Sixty-five percent had undergone aortic surgery compared to 39% at baseline. Pulmonary trunk mean diameter had increased significantly compared to baseline. From inclusion to follow-up, two patients (three eyes) developed ectopia lentis, four developed dural ectasia, four developed scoliosis, three developed incisional or recurrent herniae, and 14 developed hindfoot deformity. No changes were found regarding protrusio acetabuli, spontaneous pneumothorax, or striae atrophicae. The study confirms that knowledge of incidence and progression of organ manifestations throughout life is important for diagnosis, treatment, and follow-up of patients with verified or suspected MFS.

Intra-aortic balloon pump in acute chest pain and cardiogenic shock - a long-term follow-up.

Objectives. Coronary revascularisation and intra-aortic balloon pump (IABP) has been considered the gold standard treatment of acute coronary syndrome with cardiogenic shock, recently challenged by the SHOCK II study. The aim of this non-randomised study was to investigate the long term prognosis after immediate IABP supported angiography, in patients with acute chest pain and cardiogenic shock, treated with percutaneous coronary intervention (PCI), cardiac surgery or optimal medical treatment. We assessed data from 281 consecutive patients admitted to our department from 2004 to 2010. Results. Mean (±SD) age was 63.8 ± 11.5 (range 30-84) years with a follow-up of 5.6 ± 4.4 (0-12.7) years. Acute myocardial infarction was the primary diagnosis in 93% of the patients, 4% presented with unstable angina pectoris and 3% cardiomyopathy or arrhythmias of non-ischemic aetiology. Systolic blood pressure at admittance was 85 ± 18 mmHg and diastolic 55 ± 18 mmHg. Thirty day, one- and five-year survival was 71.2%, 67.3% and 57.7%, respectively. PCI was performed immediately in 70%, surgery was done in 17%, and 13% were not eligible for any revascularisation. Independent variables predicting mortality were medical treatment vs revascularisation, out-of-hospital cardiac arrest, and advanced age. Three serious non-fatal complications occurred due to IABP treatment, i.e. 0.001 per treatment day. Conclusions. We report the use of IABP in patients with acute chest pain admitted for angiography. Long-term survival is acceptable and discriminating factors were no revascularisation, out-of-hospital cardiac arrest and age. IABP was safe and feasible and the complication rate was low.

Effect of Donor Age on Outcome of Lung Transplantation Stratified by Recipient Diagnosis: A Nordic Multicenter Study.

BACKGROUND: Organs from older donors are increasingly used in lung transplantation, and studies have demonstrated that this could be safe in selected recipients. However, which recipient groups that have the largest benefit of older organs are unclear. This multicenter study reviews all bilateral lung transplantations (BLTx) from donors 55 years or older stratified by recipient diagnosis and compares outcomes with transplantations from younger donors. METHODS: All BLTx recipients (excluding retransplantation) at 5 Scandiatransplant centers between 2000 and 2013 were included (n = 913). Recipients were stratified to diagnosis groups including cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), and "other." Intensive care unit (ICU) length of stay (LOS) and survival were assessed. RESULTS: Overall, there was no difference in survival among patients transplanted from donors 55 years or older compared with younger donors. However, in CF recipients, donor age 55 years or older was associated with inferior survival (P = 0.014), and this remained significant in a multivariate model (hazard ratio, 5.0; 95% confidence interval, 1.8-14.1; P = 0.002). There was no significant effect of donor age on survival in recipients with COPD, ILD, or in the "other" group in multivariate models. Utilization of older donors was associated with increased ICU LOS for recipients with CF and ILD, but not in the COPD or "other" group. CONCLUSIONS: The BLTx recipients with CF had inferior survival and longer ICU LOS when receiving organs from donors 55 years or older. Recipients with COPD, ILD, or in the "other" group did not have inferior survival in multivariate models.

Survival, causes of death, and cardiovascular events in patients with Marfan syndrome.

BACKGROUND: To explore survival, causes of death, and the prevalence of cardiovascular events in a Norwegian Marfan syndrome (MFS) cohort. MFS is a heritable connective tissue disorder associated with reduced life expectancy-primarily due to aortic pathology. METHODS: A follow-up study of 84 MFS adults, initially investigated in 2003-2004. In 2014-2015, 16 were deceased, 47 of 68 survivors consented to new clinical investigations. Analyses of events were performed for 47 survivors and 16 deceased at follow-up. Standardized mortality ratios (SMR), using the mortality rate of the Norwegian population as reference, were calculated for all 84 and calculated for men and women separately. Causes of death and information on cardiovascular events were retrieved from death certificates and medical records. RESULTS: Standardized mortality ratios (95% confidence interval): for the whole cohort: 5.24 (3.00-8.51); for men: 8.20 (3.54-16.16); for women: 3.85 (1.66-7.58). Cardiovascular causes were found in 11 of 16 deceased, eight of these related to aortic pathology. Cancer was the cause of death in three patients. At follow-up, 51% had new cardiovascular events; 59% had undergone aortic surgery. Men experienced aortic events at younger age than women. 32% of the survivors were not followed-up as recommended. CONCLUSION: Life expectancy is reduced in this MFS cohort compared to the Norwegian population. Cardiovascular complications develop throughout life, particularly aortic pathology, the major cause of death in MFS. Death and aortic pathology seem to occur earlier in men. There is a need to improve follow-up according to guidelines.

Cardiovascular surgery in Loeys-Dietz syndrome types 1-4.

OBJECTIVES: The first publication of Loeys-Dietz syndrome (LDS) described aortic rupture at young ages. Experience with new LDS types showed that the clinical course varies, and thresholds for prophylactic surgery are discussed. As this is an uncommon disease, experience needs to be shared. METHODS: Retrospective review of patients with LDS types 1-4 undergoing cardiovascular surgery during the years 1991-2016. RESULTS: Thirty-five patients (including 6 children with LDS2) underwent 57 operations. LDS 1, 2, 3 and 4 included 4, 17, 11 and 3 patients, respectively. Mean age at first surgery was 36 years, with a non-significant trend that LDS2 patients were younger. Of the 9 emergency surgeries, 7 were type A dissections, with 1 postoperative death. Twenty-two patients had prophylactic aortic root surgery (17 valve-sparing root replacements), with 1 postoperative death, 1 reoperation with valve replacement and 1 late death. Freedom from root reintervention and death was 92% at 13 years. Of the 11 patients with LDS3, 5 needed mitral valve surgery. Mitral valve disease was not found in the other LDS types. Ten patients needed >1 operation. Of the 57 operations, 33 were in the ascending aorta, 20 in the aorta distal to the arch including branches and 4 were isolated heart surgeries. Of the 20 vascular operations, 16 were in LDS2. Cumulative survival 20 years after first surgery (all patients) was 94.3%. CONCLUSIONS: Clinical course seems to be more aggressive in LDS2, with index operation at a younger age, and higher risk of needing several operations. Vascular disease distal to the arch is not uncommon. LDS3 seems to be associated with mitral valve disease. Prophylactic aortic root surgery is safe and durable.

Karl Viktor Hall: From In Situ Vein Bypass to the Tilting Disc Heart Valve Prosthesis.

In 1977, Karl Viktor Hall implanted a novel tilting disc heart valve prosthesis at Rikshospitalet in Oslo, Norway. The Medtronic-Hall valve was known for its excellent durability and low thrombogenicity. Hall popularized the use of the great saphenous vein in situ as an arterial shunt in the 1960s, made a metal stripper to lyse vein valves, and introduced electromagnetic flowmeters in vascular surgery. He performed the first coronary artery bypass graft in Scandinavia in 1969. Under his leadership the first heart transplantation and the first heart-lung transplantation were performed in Scandinavia by his successor Tor Frøysaker in 1983 and 1986, respectively.

Altered Levels of Fatty Acids and Inflammatory and Metabolic Mediators in Epicardial Adipose Tissue in Patients With Systolic Heart Failure.

BACKGROUND: Adipose tissue has endocrine properties, secreting a wide range of mediators into the circulation, including factors involved in cardiovascular disease. However, little is known about the potential role of adipose tissue in heart failure (HF), and the aim of this study was to investigate epicardial (EAT) and subcutaneous (SAT) adipose tissue in HF patients. METHODS AND RESULTS: Thirty patients with systolic HF and 30 patients with normal systolic function undergoing thoracic surgery were included in the study. Plasma was sampled and examined with the use of enzyme-linked immunosorbent assays, whereas SAT and EAT biopsies were collected and examined by means of reverse-transcription polymerase chain reaction and gas chromatography. Significantly higher expressions of mRNA encoding interleukin-6, adrenomedullin, peroxisome proliferator-activated receptor α, and fatty acid (FA)-binding protein 3, as well as higher levels of monounsaturated FA and palmitoleic acid, were seen in the EAT of HF patients, whereas the levels of docosahexaenoic acid were lower. Palmitoleic acid levels in EAT were correlated with 2 parameters of cardiac remodeling: increasing left ventricular end-diastolic diameter and N-terminal pro-B-type natriuretic peptide. CONCLUSIONS: Our results demonstrate adipose tissue depot-specific alterations of synthesis of FA and inflammatory and metabolic mediators in systolic HF patients. EAT may be a source of increased circulatory and myocardial levels of these mediators through endocrine actions.

Multiorgan procurement increases systemic inflammation in brain dead donors.

Organs available for solid organ transplantation are mainly procured from brain dead donors. The inflammation associated with brain death may reduce organ quality and increase organ immunogenicity, thus leading to inferior recipient outcome. We hypothesized that the extensive surgical procedure performed during multiorgan procurement enhances the levels of systemic inflammatory biomarkers. We measured the levels of 27 cytokines and the terminal complement complex (TCC) in plasma samples from brain dead organ donors (n = 34) drawn before and at three specific time points during procurement surgery. Baseline levels of G-CSF, interferon-γ, IL-1ra, IL-4, IL-6, IL-7, IL-8, IL-10, IP-10, MCP-1, macrophage inflammatory protein (MIP)-1ß, platelet derived growth factor (PDGF), regulated upon activation T cell expressed and secreted, and tumor necrosis factor-α were significantly elevated in brain dead donors compared with normal individuals (n = 14), but they were not associated with time on ventilator or any other registered clinical variable. Notably, the secretion of G-CSF, IL1-ra, IL-6, IL-8, IL-10, IP-10, MCP-1, MIP-1ß, PDGF, and TCC, the latter reflecting ongoing complement activation, increased significantly during surgery. None of the biomarker increases were correlated with operation duration. Multiorgan procurement surgery significantly adds to the inflammatory response revealed by both pro- and anti-inflammatory biomarkers associated with brain death. Future studies should determine whether this is associated with inferior recipient outcome.

Heart transplant systolic and diastolic function is impaired by prolonged pretransplant graft ischaemic time and high donor age: an echocardiographic study.

OBJECTIVES: Due to the need for suitable donors for heart transplantation (HTx), older grafts and grafts with prolonged graft ischaemic time (GIT) are accepted. The impact of GIT and donor age on post-transplant cardiac function has not been examined with either newer echocardiographic techniques (tissue Doppler imaging, TDI) or cardiopulmonary exercise testing (CPET). Thus, we studied the influence of GIT and donor age on post-transplant cardiac function and exercise capacity. METHODS: Fifty-two stable recipients underwent echocardiography with colour TDI and CPET at a median of 4 years after HTx. Left ventricular (LV) systolic (s') and early diastolic (e') mitral annular velocities, right ventricular (RV) s', RVe' as well as LV ejection fraction (EF) and VO(2peak) were analysed. RESULTS: HTx recipients with GIT ≥ median value (200 min) had significantly lower septal LVs' (15%, P = 0.005), LVEF (9%, P = 0.015), RVs' (21%, P = 0.007), septal LVe' (22%, P = 0.001) and RVe' velocities (23%, P = 0.011), and slightly lower VO(2peak) (P = 0.098). Recipients with grafts from donor ≥ median age (37 years) had significantly lower LVe' velocities (septal LVe' P = 0.047 and lateral LVe' P = 0.010), but not LV systolic or RV parameters. CONCLUSIONS: Prolonged GIT impairs both systolic and diastolic function at the interventricular septum and RV free wall, while increasing donor age impairs LV diastolic function. The duration of graft ischaemia and donor age should be taken into account when evaluating for cardiac dysfunction in HTx recipients.

Three decades of heart transplantation in Scandinavia: long-term follow-up.

AIM: Heart transplantation (HTx) has become a standard treatment for patients with end-stage heart disease. The aim of this study was to report the long-term outcome after HTx in Scandinavia. METHODS AND RESULTS: During the period, 1983-2009, 2333 HTxs were performed in 2293 patients (mean age 45 ± 16 years, range 0-70, 78% male). The main indications for HTx were non-ischaemic cardiomyopathy (50%), ischaemic cardiomyopathy (34%), valvular cardiomyopathy (3%), congenital heart disease (7%), retransplantation (2%), and miscellaneous (4%). The registry consists of pre-operative data from recipients and donors, data from pre-operative procedures, and long-term follow-up data. Mean follow-up was 7.8 ± 6.6 years (median 6.9, interquartile range 2.5-12.3, interval 0-27) and no patients were lost to follow-up. Long-term survival for HTx patients was 85, 76, 61, 43, and 30% at 1, 5, 10, 15, and 20 years of follow-up, respectively. Ten-year survival in patients bridged with mechanical circulatory support, in children, after retransplantation, and after concomitant other organ transplantation was 56, 74, 38, and 43%, respectively. Older patients (age > 55 years) had a significantly worse survival (P < 0.001). Patients transplanted more recently had a significantly better survival (P < 0.001). In a multivariate Cox regression analysis, independent predictors of long-term survival were recipient age (P < 0.001), donor age (P < 0.001), diagnosis (P = 0.001), and era of transplantation (P < 0.001). CONCLUSIONS: HTx in Scandinavia proves to have a significantly better survival among patients transplanted in the last decade. HTxs from mechanical circulatory support, in children, after retransplantation, and with concomitant other organ transplantation were performed with acceptable results.

Hospital costs fell as numbers of LVADs were increasing: experiences from Oslo University Hospital.

BACKGROUND: The current study was undertaken to examine total hospital costs per patient of a consecutive implantation series of two 3rd generation Left Ventricle Assist Devices (LVAD). Further we analyzed if increased clinical experience would reduce total hospital costs and the gap between costs and the diagnosis related grouped (DRG)-reimbursement. METHOD: Cost data of 20 LVAD implantations (VentrAssist™) from 2005-2009 (period 1) were analyzed together with costs from nine patients using another LVAD (HeartWare™) from 2009-June 2011 (period 2). For each patient, total costs were calculated for three phases - the pre-LVAD implantation phase, the LVAD implantation phase and the post LVAD implant phase. Patient specific costs were obtained prospectively from patient records and included personnel resources, medication, blood products, blood chemistry and microbiology, imaging and procedure costs including operating room costs. Overhead costs were registered retrospectively and allocated to the specific patient by predefined allocation keys. Finally, patient specific costs and overhead costs were aggregated into total hospital costs for each patient. All costs were calculated in 2011-prices. We used regression analyses to analyze cost variations over time and between the different devices. RESULTS: The average total hospital cost per patient for the pre-LVAD, LVAD and post-LVAD for period 1 was $ 585, 513 (range 132, 640- 1 247, 299), and the corresponding DRG- reimbursement (2009) was $ 143, 192 . The mean LOS was 54 days (range 12- 127). For period 2 the total hospital cost per patient was $ 413, 185 (range 314, 540- 622, 664) and the corresponding DRG- reimbursement (2010) was $ 136, 963. The mean LOS was 49 days (range 31- 93).The estimates from the regression analysis showed that the total hospital costs, excluding device costs, per patient were falling as the number of treated patients increased. The estimate from the trend variable was -14, 096 US$ (CI -3, 842 to -24, 349, p < 0.01). CONCLUSION: There were significant reductions in total hospital costs per patient as the numbers of patients were increasing. This can possibly be explained by a learning effect including better logistics, selection and management of patients.

Health-related quality of life in Marfan syndrome: a cross-sectional study of Short Form 36 in 84 adults with a verified diagnosis.

PURPOSE: To explore health-related quality of life as measured with Short Form 36 in adults with verified Marfan syndrome and to compare with the general population, other groups with chronic problems and studies on Marfan syndrome. Furthermore, to study potential correlations between the scores on the subscales of Short Form 36 and the presence of biomedical criteria and symptoms of Marfan syndrome. METHOD: Cross-sectional study. Short Form 36 was investigated in 84 adults with verified Marfan syndrome. RESULTS: The study group had reduced scores on all eight subscales of Short Form 36 compared with the general population, comparable with other groups with chronic diseases. Compared with earlier Short Form 36 results in Marfan syndrome, we found lower scores for social function, vitality, general health, bodily pain, and role physical. No correlations of substantial explanatory values were found between the Short Form 36 subscales and gender, body mass index, ascending aortic surgery, use of beta-blockers, visual acuity, joint hypermobility, fulfillment of the five major Ghent criteria, and number of major criteria fulfilled. Potential explanations are discussed. CONCLUSION: Persons with Marfan syndrome have reduced scores for health-related quality of life as measured with Short Form 36, comparable with those in other chronic disorders and disabilities. The reduction does not seem to be related to biomedical criteria or symptoms of Marfan syndrome.

The prognostic importance of modifiable risk factors after heart transplantation.

BACKGROUND: It is well established that the treatment of modifiable risk factors can reduce cardiovascular mortality in the general population. However, there is limited data evaluating the importance of modifiable risk factors for survival following heart transplantation (HTx). Hence, we evaluated the prognostic importance of smoking, obesity, hyperglycemia and hyperlipidemia at 1 year after HTx for all-cause and cardiac mortality. METHODS: We evaluated 381 patients attending their first annual visit post-HTx. Data regarding modifiable risk factors was collected together with other clinical variables. Median follow-up time was 7.4 years. RESULTS: In total, there were 122 (32%) deaths and smoking and elevated total cholesterol were independent risk factors for all-cause mortality (adjusted HR 1.6 [P = .02] and 1.8 [P = .003], respectively). A significantly higher incidence of cardiac death was noted amongst smokers and patients with elevated total cholesterol. Elevated body mass index and hemoglobin A(1c) did not affect prognosis and elevated total cholesterol was not a risk factor once statin therapy commenced at the time of HTx was instituted as protocol. CONCLUSIONS: Smoking is a risk factor for all-cause and cardiac mortality, but elevated total cholesterol is a risk factor only in the absence of statin therapy being commenced at the time of HTx.

Surgical repair of postinfarction ventricular septal rupture: risk factors of early and late death.

OBJECTIVE: The aim of the study was to identify risk factors of early and late death after surgical repair of postinfarction ventricular septal rupture. METHODS: During a 25-year period, from May 1981 to August 2006, 102 patients underwent repair of postinfarction ventricular septal rupture. Data were collected on clinical, angiographic, and echocardiographic findings; operative procedures; early morbidity; and survival time. Univariable and multivariable analyses were performed to identify risk factors of 30-day mortality and total mortality. RESULTS: Thirty-day mortality was 33% altogether and decreased from 45% in the first half to 21% in the second half of the period (P = .01). Follow-up was a mean of 5.2 +/- 6.2 years and a median of 2.9 years (range, 0-26.3 years). Five- and 10-year cumulative survival was 50% and 32%, respectively. Shock at surgical intervention and incomplete coronary revascularization were strong and independent risk factors of both 30-day mortality and poor long-term survival. CONCLUSIONS: Early outcome after repair of ventricular septal rupture improved significantly during time, with 30-day mortality being 21% in the last decade. Five- and 10-year cumulative survival was 50% and 32%, respectively. Shock at surgical intervention and incomplete coronary revascularization were strong and independent predictors of poor early and late survival.

Thoracic aortic aneurysm repair. Direct hospital cost and Diagnosis Related Group reimbursement.

OBJECTIVE: The main objective of this study was to analyze direct hospital cost and to compare cost with existing DRG reimbursement for open repair of thoracic and thoraco-abdominal aortic disease. STUDY SAMPLE AND METHODOLOGY: Between January 2003 and September 2003, the cost of treatment for 24 surgical procedures on ascending aorta and arch, descending or thoraco-abdominal aortic disease were examined prospectively. Seven patients had urgent or emergency surgeries. Ten had sternotomies for disease of the ascending aorta and aortic arch; two had left thoracotomies and three thoraco-laparotomy incisions with procedures performed on x-corporeal circulation. Nine other patients had more distal thoraco-abdominal aortic operations with a clamp-and-sew technique. Micro-cost analysis was performed on each hospital stay, in addition overhead hospital costs were allocated to each procedure. RESULTS: The patients were grouped by discharge diagnosis (ICD-10) and surgical procedure performed (NCSP) into Norwegian DRG code. Patient with surgery on ascending aorta & aortic arch were allocated to DRG 108 (n=9) or 483 (tracheostomy, n=1) while patient with surgery on descending or thoraco-abdominal aorta were allocated to DRG 108 (n=3), 110 (n=4), 111 (n=4) or 483 (tracheostomy, n=3). The mean EuroSCORE for patients with proximal aortic disease was 11 (5-18), and the length of stay was 5 days (range 3-8 days), spending 2 days (range 1-7 days) in thoracic intensive care unit. For patients with distal aortic disease the mean Euroscore was 7 (2-14), and the mean length of stay 10 days (range 4-23 days) with a mean 4 days (range 1-13 days) in intensive care unit. Eight patients developed medical problems requiring new surgical procedures or prolonged ICU stay. The average direct hospital cost for proximal aortic surgery was USD 15,877 (USD 1=NOK 7.5) while the respective 100% DRG reimbursement including one patient needing a tracheostomy, was 19 803 USD. For patients with distal aortic disease, average direct hospital cost was 23 005 USD and DRG reimbursement including patients needing a tracheostomy was 31543 USD. CONCLUSION: Our results underscore previous findings that these patients are resource intensive. This study shows that Norwegian 100% DRG reimbursement did over-compensate observed total hospital costs in this cohort. Detailed analysis showed that this was due to the higher DRG reimbursement for patients needing prolonged ventilatory support. Thus the actual DRG reimbursement seems to be relevant to the tertiary hospital actual costs when these complicated patients are considered as a group. It remains however unclear whether this reimbursement is sufficient to support the scientific infrastructure for new knowledge and skills needed for the further refinement of treatment.

Probrain natriuretic peptide and C-reactive protein as markers of acute rejection, allograft vasculopathy, and mortality in heart transplantation.

BACKGROUND: N-terminal probrain natriuretic peptide (NT-proBNP) and C-reactive protein (CRP) are useful in risk stratification of patients with congestive heart failure. They could also be markers of distinctly altered hormonal and immunological milieus, but the combined prognostic value of these biomarkers in heart transplant (HTx) recipients has not been assessed previously. METHODS: We sought to assess the individual and combined value of NT-proBNP and CRP as markers of acute rejection, cardiac allograft vasculopathy (CAV) and all-cause mortality in HTx recipients. We evaluated 101 patients for acute rejection and 210 patients for CAV and all-cause mortality. Patients evaluated for rejection had serial endomyocardial biopsies and plasma sampling performed during the first year postHTx. All other patients had plasma samples taken upon inclusion at an annual visit. Median follow-up for CAV and all-cause mortality was 2.2 years and 5.4 years, respectively. RESULTS: Altogether, 1131 biopsy procedures were performed, and increased NT-proBNP and CRP levels were not useful markers of acute cellular rejection. In total, 78 (37%) patients developed CAV, and 39 (19%) patients died. Neither biomarker was a predictor of CAV, but both were independent predictors of mortality. When combining both biomarkers, elevated levels of both NT-proBNP and CRP identified patients at highest risk for CAV (HR 2.10, P=0.01) and all-cause mortality (HR 3.14, P=0.01). CONCLUSIONS: In HTx recipients, NT-proBNP and CRP are not useful as markers of acute cellular rejection during the first year postHTx, but combined analysis adds significantly to their predictive value for development of CAV and all-cause mortality.

[Survival after heart transplantation in Norway]. / Overlevelse etter hjertetransplantasjon i Norge.

BACKGROUND: 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. MATERIAL AND METHODS: 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. RESULTS AND INTERPRETATION: 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 transplantation have the best prognosis regardless of donor age, while the combination of patients older than 50 years and donor above 35 years have the poorest chance of survival. However, patients are disposed to various severe complications. Initially after transplantation acute rejection, unspecific graft failure and infections are a threat; while complications such as chronic graft sclerosis, renal failure and cancer are complications that appear over time. To optimise results, life-long regular follow up is necessary.

Bacterial diversity in aortic aneurysms determined by 16S ribosomal RNA gene analysis.

BACKGROUND: Aortic aneurysms are common vascular conditions that cause considerable morbidity and mortality. Understanding of the mechanisms involved in the pathogenesis of the condition remains limited. Recently, infection has been suggested as possible contributor in the development of the disease. The aim of the present study was to examine aortic aneurysms for the presence of bacterial DNA using polymerase chain reaction (PCR) targeting the 16S ribosomal RNA (rRNA) gene, followed by cloning and sequencing. METHODS: Universal eubacterial primers were used to amplify 16S rRNA bacterial genes in 10 specimens from arterial walls of aortic aneurysms. Subsequently, PCR amplicons were cloned into Escherichia coli and sequencing of the cloned inserts was used to determine species identity or closest relatives by comparison with known sequences in GenBank. RESULTS: Sequences of Stenotrophomonas spp., including S. maltophilia (formerly Pseudomonas homology group V) were detected in six aneurysm samples. Propionibacterium acnes was identified in five samples, and Brevundimonas diminuta (formerly P. diminuta) in four samples. Other species previously assigned to the Pseudomonas genus such as Comamonas testosteroni, Delftia acidovorans, Burkholderia cepacia, Herbaspirillum sp., and Acidovorax sp. were also detected. Some clones fell into other environmental species, including Methylobacterium sp. and Bradyrhizobium elkanii, and others represented bacteria that have not yet been cultivated. DNA sequences from oral bacteria, including Streptococcus sanguinis, Tannerella forsythia, and Leptotrichia buccalis were detected. Sequences from Prevotella melaninogenica and Lactobacillus delbrueckii, which are commonly found in both mouth and gastrointestinal tract, were also detected. Additional species included Dermacoccus spp. and Corynebacterium vitaeruminis. CONCLUSIONS: A wide variety of bacteria, including oral bacteria, was found to colonize aortic aneurysms and may play a role in their development. Several of these microorganisms have not yet been cultivated. CLINICAL RELEVANCE: Although Chlamydophila pneumoniae has been detected in aneurysmal walls, its exact role in the condition remains inconclusive. Overall, there is scarce information about the role of microorganisms in aneurysmal disease. In the present study, we used molecular genetics to detect a diversity of bacteria in arterial walls of aortic aneurysms. The presence of multiple microorganisms in aneurysmal disease may have implications for chemoprophylaxis and antibiotic treatment if directed only at C.pneumoniae.

Decreased endomyocardial RANKL expression in transplant coronary artery disease.

Transplant-associated coronary artery disease (TxCAD) appears to be initiated by endothelial cell activation and inflammation involving inflammatory cytokines and chemokines. Osteoprotegerin (OPG) and receptor activator of nuclear Factor-kappaB ligand (RANKL) have been implicated in cardiovascular disease progression and we measured the expression of these mediators in serum and myocardial biopsies taken serially during the first year after heart transplantation (HTx), relating them to the development of TxCAD. Serum OPG as well as myocardial gene expression of RANK and OPG, but not RANKL, were highest early after HTx and declined progressively. Importantly, patients who develop TxCAD or experience episodes of acute rejection showed a lower myocardial RANKL expression throughout the first year after transplantation than patients without these complications. Our findings may suggest an unrecognized role RANKL in maintaining myocardial and/or endothelial integrity and suggest that RANKL should be further investigated as a parameter that may predict development of TxCAD.