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Introduction: Anticitrullinated peptide antibody (ACPA) responses for 22 citrullinated peptides in patients with early rheumatoid arthritis (RA) were analysed and related to radiological and clinical outcome during the first 2 years in a prospective inception cohort., Methods: The ACPA reactivities were assessed in 1022 patients with early RA (symptoms <12 months) using the custom-made microarray chip (Thermo Fisher Scientific, Uppsala, Sweden) in a prospective longitudinal study of observational assessments of Disease Activity Score (DAS28 and its components) and radiology during the first 24 months, accounting for the treatment., Results: Frequency of ACPA reactivities varied between 13.3% and 63.1%. Of the anticyclic citrullinated peptide-2 (anti-CCP2) antibody-negative patients, ACPA reactivities were positive in 32.6%. Smoking, human leucocyte antigen-shared epitope (HLA-SE), anti-CCP2/rheumatoid factor, protein tyrosine phosphatase non-receptor type 22 (1858C/T) and DAS28 were significantly associated with number of ACPA reactivities. The ACPA reactivities modified differently the development of DAS28 over 24 months (identified using trajectories). Anti-Filaggrin307-324, anti-hnRNP (Peptide)-Z1 and anti-F4-CIT-R antibodies anticipated lower DAS28 values (p<0.01-0.05), while positivity for anti-Fibrinogen(Fib)β62-78(74), and anti-Fibα563-583 predicted higher DAS28 (p<0.01 both). Interaction between anti-Fibß36-52, anti-Pept-5 and anti-Bla-26 antibodies, respectively, and DAS28 during 24 months decreased significantly the DAS28 values (p<0.01-0.05). Corticosteroids and biologicals were related to DAS28-area under the curve and Larsen score 24 months. Anti-vimentin2-17 antibodies remained significantly associated with Larsen score at baseline and 24 months, respectively, and radiological progression, besides biologicals at 24 months adjusted for sex and age., Conclusions: Several ACPA reactivities modified significantly the DAS28 development during the first 24 months and were significantly associated with Larsen score at baseline, 24 months and radiological progression., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Periarticular osteopenia is an early sign of incipient joint injury in rheumatoid arthritis (RA), but cannot be accurately quantified using conventional radiography. Digital X-ray radiogrammetry (DXR) is a computerized technique to estimate bone mineral density (BMD) from hand radiographs. The aim of this study was to evaluate whether decrease in BMD of the hands (BMD loss), as determined by DXR 3 months after diagnosis, predicts radiographic joint damage after 1 and 2 years in patients with early RA., Methods: Patients (n = 176) with early RA (<12 months after onset of symptoms) from three different Swedish rheumatology centers were consecutively included in the study, and 167 of these patients were included in the analysis. Medication was given in accordance with Swedish guidelines, and the patients were followed for 2 years. Rheumatoid factor and antibodies to cyclic citrullinated peptides (anti-CCP) were measured at baseline, and 28-joint Disease Activity Score (DAS28) was assessed at each visit. Radiographs of the hands and feet were obtained at baseline, 3 months (hands only) and 1 and 2 years. Baseline and 1-year and 2-year radiographs were evaluated by the Larsen score. Radiographic progression was defined as a difference in Larsen score above the smallest detectable change. DXR-BMD was measured at baseline and after 3 months. BMD loss was defined as moderate when the decrease in BMD was between 0.25 and 2.5 mg/cm 2 /month and as severe when the decrease was greater than 2.5 mg/cm 2 /month. Multivariate regression was applied to test the association between DXR-BMD loss and radiographic damage, including adjustments for possible confounders., Results: DXR-BMD loss during the initial 3 months occurred in 59% of the patients (44% moderate, 15% severe): 32 patients (19%) had radiographic progression at 1 year and 45 (35%) at 2 years. In multiple regression analyses, the magnitude of DXR-BMD loss was significantly associated with increase in Larsen score between baseline and 1 year (p = 0.033, adjusted R-squared = 0.069)., Conclusion: DXR-BMD loss during the initial 3 months independently predicted radiographic joint damage at 1 year in patients with early RA. Thus, DXR-BMD may be a useful tool to detect ongoing joint damage and thereby to improve individualization of therapy in early RA.

The aim of this study was to analyze relationships between receptor activator of nuclear factor kappa-B (RANKL), sclerostin and their gene polymorphisms with radiological progression in patients with early rheumatoid arthritis (RA). Patients with early RA (n = 407, symptomatic <1 year) (ARA criteria) examined radiologically at inclusion and after 24 months were consecutively included. Disease activity score and C-reactive protein were regularly recorded. Sclerostin, RANKL, and anti-CCP2 antibodies were analyzed in plasma at baseline using ELISAs. Data on gene polymorphism for sclerostin and RANKL were extracted from Immunochip analysis. Sex- and age-matched controls (n = 71) were identified from the Medical Biobank of Northern Sweden. The concentration of RANKL was significantly higher in patients compared with controls, median (IQR) 0.56 (0.9) nmol/L and 0.20 (0.25) nmol/L (p < 0.001), and in anti-CCP2-positive patients compared with sero-negative individuals. Sclerostin was significantly increased in female patients 0.59 (0.47-0.65) ng/mL compared with female controls 0.49 (0.4-0.65) ng/mL (p < 0.02). RANKL concentration was related to the Larsen score at baseline (p < 0.01), after 24 months (p < 0.001), and to radiological progression at 24 months (p < 0.001). Positivity of RANKL and anti-CCP2 yielded significant risk for progression with negativity for both as reference. No single nucleotide polymorphism encoding TNFSF11 or SOST was associated with increased concentrations of the factors. The concentration of RANKL was related to the Larsen score at baseline, at 24 months, and radiological progression at 24 months particularly in anti-CCP2-positive patients, while the concentration of sclerostin was unrelated to radiological findings.

Introduction: The western population is ageing. It is unknown whether age at diagnosis affects the severity of Rheumatoid Arthritis (RA), we therefore performed the present study., Method: 1,875 RA-patients (7,219 radiographs) included in five European and North-American cohorts (Leiden-EAC, Wichita, Umeå, Groningen and Lund) were studied on associations between age at diagnosis and joint damage severity. In 698 Leiden RA-patients with 7-years follow-up it was explored if symptom duration, anti-citrullinated-peptide-antibodies (ACPA), swollen joint count (SJC) and C-reactive-protein (CRP) mediated the association of age with joint damage. Fifty-six other RA-patients of the EAC-cohort underwent baseline MRIs of wrist, MCP and MTP-joints; MRI-inflammation (RAMRIS-synovitis plus bone marrow edema) was also evaluated in mediation analyses. Linear regression and multivariate normal regression models were used., Results: Analysis on the five cohorts and the Leiden-EAC separately revealed 1.026-fold and 1.034-fold increase of radiographic joint damage per year increase in age (β=1.026, 1.034, both p<0.001); this effect was present at baseline and persisted over time. Age correlated stronger with baseline erosion-scores compared to joint space narrowing (JSN)-scores (r=0.38 versus 0.29). Symptom duration, ACPA, SJC and CRP did not mediate the association of age with joint damage severity. Age was significantly associated with the MRI-inflammation-score after adjusting for CRP and SJC (β=1.018, p=0.027). The association of age with joint damage (β=1.032, p=0.004) decreased after also including the MRI-inflammation-score (β=1.025, p=0.021), suggesting partial mediation., Conclusion: RA-patients presenting at higher age have more severe joint damage; this might be partially explained by more severe MRI-detected inflammation at higher age.

Introduction: The presence of a new autoantibody system, anti-carbamylated protein (anti-CarP) antibodies, has been identified in rheumatoid arthritis (RA). The presence of anti-CarP antibodies was evaluated in samples taken from individuals who subsequently developed RA before and after onset of symptoms and related to previously analysed antibodies against citrullinated peptides (ACPA specificities) and anti-CCP2., Methods: A total of 252 individuals, with 423 samples from before onset of symptoms of RA, and 197 population controls were identified as donors to the Medical Biobank of Northern Sweden; 192 of them were also sampled at the time of diagnosis. All samples were analysed for anti-CarP IgG and anti-CCP2 antibodies using ELISAs. Ten different antibody reactivities against citrullinated antigens (ACPA specificities) were analysed using a custom-made microarray based on the ImmunoCAP ISAC system (Phadia)., Results: The concentration of anti-CarP antibodies was significantly increased in the pre-symptomatic individuals compared with controls (P<0.001) and also increased significantly after disease onset (P<0.001). The sensitivity for anti-CarP antibodies in the pre-symptomatic individuals was 13.9% (95% CI: 11 to 17.6) and 42.2% (95% CI: 35.4 to 49.3) following development of RA. Anti-CarP antibody positivity was found in 5.1% to 13.3% of individuals negative for anti-CCP2 or ACPA specificities. Presence of anti-CarP antibodies was significantly related to radiological destruction at baseline, at 24 months and also to radiological change (P<0.05, all)., Conclusions: The results indicate that anti-CarP antibodies are associated with disease development, even after adjusting for the presence of different ACPA fine specificities, and in anti-CCP2 negative individuals and contribute to the identification of a subset of patients with worse radiological progression of the disease independent of ACPA.

Introduction: The severity of joint damage progression in rheumatoid arthritis (RA) is heritable. Several genetic variants have been identified, but together explain only part of the total genetic effect. Variants in Interleukin-6 (IL-6), Interleukin-10 (IL-10), C5-TRAF1, and Fc-receptor-like-3 (FCRL3) have been described to associate with radiographic progression, but results of different studies were incongruent. We aimed to clarify associations of these variants with radiographic progression by evaluating six independent cohorts., Methods: In total 5,895 sets of radiographs of 2,493 RA-patients included in six different independent datasets from the Netherlands, Sweden, Spain and North-America were studied in relation to rs1800795 (IL-6), rs1800896 (IL-10), rs2900180 (C5-TRAF1) and rs7528684 (FCRL3). Associations were tested in the total RA-populations and in anti-citrullinated peptide antibodies (ACPA)-positive and ACPA-negative subgroups per cohort, followed by meta-analyses. Furthermore, the associated region C5-TRAF1 was fine-mapped in the ACPA-negative Dutch RA-patients., Results: No associations were found for rs1800795 (IL-6), rs1800896 (IL-10) and rs7528684 (FCRL3) in the total RA-population and after stratification for ACPA. Rs2900180 in C5-TRAF1 was associated with radiographic progression in the ACPA-negative population (P-value meta-analysis = 5.85 × 10(-7)); the minor allele was associated with more radiographic progression. Fine-mapping revealed a region of 66Kb that was associated; the lowest P-value was for rs7021880 in TRAF1. The P-value for rs7021880 in meta-analysis was 6.35 × 10(-8). Previous studies indicate that the region of rs7021880 was associated with RNA expression of TRAF1 and C5., Conclusion: Variants in IL-6, IL-10 and FCRL3 were not associated with radiographic progression. Rs2900180 in C5-TRAF1 and linked variants in a 66Kb region were associated with radiographic progression in ACPA-negative RA.

Introduction: Disease activity, severity and comorbidity contribute to increased mortality in patients with rheumatoid arthritis (RA). We evaluated the impact of age at disease onset on prognostic risk factors and treatment in patients with early disease., Methods: In this study, 950 RA patients were followed regularly from the time of inclusion (<12 months from symptom onset) for disease activity (erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tender and/or swollen joints, Visual Analogue Scale pain and global scores, and Disease Activity Score in 28 joints (DAS28)) and function (Health Assessment Questionnaire (HAQ)). Disease severity, measured on the basis of radiographs of the hands and feet (erosions based on Larsen score), extraarticular disease, nodules, and comorbidities and treatment (disease-modifying antirheumatic drugs (DMARDs), corticosteroids, biologics and nonsteroidal anti-inflammatory drugs) were recorded at the time of inclusion and at 5 years. Autoantibodies (rheumatoid factor, antinuclear antibodies and antibodies against cyclic citrullinated peptides (ACPAs)) and genetic markers (human leucocyte antibody (HLA) shared epitope and protein tyrosine phosphatase nonreceptor type 22 (PTPN22)) were analysed at the time of inclusion. Data were stratified as young-onset RA (YORA) and late-onset RA (LORA), which were defined as being below or above the median age at the time of onset of RA (58 years)., Results: LORA was associated with lower frequency of ACPA (P < 0.05) and carriage of PTPN22-T variant (P < 0.01), but with greater disease activity at the time of inclusion measured on the basis of ESR (P < 0.001), CRP (P < 0.01) and accumulated disease activity (area under the curve for DAS28 score) at 6 months (P < 0.01), 12 months (P < 0.01) and 24 months (P < 0.05), as well as a higher HAQ score (P < 0.01) compared with YORA patients. At baseline and 24 months, LORA was more often associated with erosions (P < 0.01 for both) and higher Larsen scores (P < 0.001 for both). LORA was more often treated with corticosteroids (P < 0.01) and less often with methotrexate (P < 0.001) and biologics (P < 0.001). YORA was more often associated with early DMARD treatment (P < 0.001). The results of multiple regression analyses supported our findings regarding the impact of age on chosen treatment., Conclusion: YORA patients were more frequently ACPA-positive than LORA patients. LORA was more often associated with erosions, higher Larsen scores, higher disease activity and higher HAQ scores at baseline. Nevertheless, YORA was treated earlier with DMARDs, whilst LORA was more often treated with corticosteroids and less often with DMARDs in early-stage disease. These findings could have implications for the development of comorbidities.

Background: To report a long-term single-site experience of the cut-and-sew Cox maze III procedure for atrial fibrillation (AF)., Methods: A total of 232 consecutive patients underwent the Cox maze III procedure for symptomatic therapy-refractory AF, with concomitant surgery in 34 patients. Follow-up data were obtained from electrocardiograms, patient visits, questionnaires, and medical files., Results: There were 103 patients (44%) with paroxysmal AF during 8.8 ± 6.5 years and 129 patients (56%) with nonparoxysmal AF for 7.3 ± 6.7 years. The preoperative New York Heart Association class was better in patients with paroxysmal AF (P < 0.0001); the left ventricular ejection fraction was 59 ± 7% versus 56 ± 8%, P = 0.003, and the left atrial area 24 ± 6 versus 27 ± 6 cm(2) , P = 0.01. Early and late postoperative adverse events occurred at similar rates. Four patients from each group died of reasons unrelated to surgery. The mean follow-up was 66 ± 42 (5-155) months. In total, 184/229 (80%) patients were free of documented AF/atrial flutter/atrial tachycardia (AF/AFl/AT) off antiarrhythmic drugs (AA) and 189/229 (83%) on or off AA. The hazard ratio (HR) for paroxysmal versus nonparoxysmal AF patients regarding documented AF/AFl/AT was 0.8 (95% confidence interval [CI] 0.4-1.4; P = 0.40). For patients without versus with concomitant surgery, the corresponding HR was 0.4 (95% CI 0.2-0.8; P = 0.008). Of 197 patients (89%) responding to the questionnaire, 41 had sought care for symptoms of arrhythmia, 29 of whom had documented AF/AFl/AT, whereas another six had other arrhythmias., Conclusion: Cut-and-sew Cox maze III surgery provided long-lasting high efficacy, also in patients with nonparoxysmal AF of long duration and/or concomitant surgery, and was associated with low rates of subsequent adverse events., (©2013, The Authors. Journal compilation ©2013 Wiley Periodicals, Inc.)

Background: The cut-and-sew Cox-maze III procedure is the gold standard for surgical treatment of atrial fibrillation. The aim was to study early and long-term mortality based on registry analyses in Swedish Cox-maze III patients., Methods: Preoperative and early postoperative data were analyzed in 536 patients (male/female (425/111), mean age 57 ± 8.6 years), operated from 1994 to 2009 in 4 centers; 422 (79%) underwent stand-alone Cox-maze III. Atrial fibrillation was paroxysmal in 38% and non-paroxysmal in 62%, mean duration was 7.8 ± 6.3 years. Patients were followed for survival or death in a validated national Cause-of-Death registry. Risk factors associated with observed survival were identified in univariable and multivariable analyses in a standard Cox proportional hazards model., Results: Four early deaths (0.7%) occurred due to technical complications. At follow-up, 41 of 536 (7.6%) patients had died. Cause of death was cardiovascular in 19 of 536 (3.5%). No ischemic stroke-related death was registered. Univariable risk factors for all-cause mortality included hypertension (hazard ratio [HR] 2.8, confidence interval [CI] 1.5 to 5.3), heart failure (HR 2.4, CI 1.3 to 4.3), concomitant surgery (HR 2.2, CI 1.1 to 4.1), and postoperative complications (HR 2.5, CI 1.3 to 4.8). Gender, non-paroxysmal atrial fibrillation and long arrhythmia duration did not confer increased risk of death. Multivariable risk factors were hypertension (HR 2.9, CI 1.5 to 5.5) and postoperative complications (HR 2.4, CI 1.2 to 4.6). Survival for cardiovascular death at 5, 10, and 15 years was 98%, 96%, and 93%, respectively., Conclusions: Registry-based follow-up showed low early and long-term cardiovascular mortality and no stroke-related mortality. This is important baseline information when evaluating current surgical and nonsurgical treatment of atrial fibrillation., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Atrial fibrillation (AF) is a common arrhythmia among patients scheduled for open heart surgery and is associated with increased morbidity and mortality. According to international guidelines, symptomatic and selected asymptomatic patients should be offered concomitant surgical AF ablation in conjunction with valvular or coronary surgery. The gold standard in AF surgery is the Cox Maze III ("cut-and-sew") procedure, with surgical incisions in both atria according to a specified pattern, in order to prevent AF reentry circuits from developing. Over 90% of patients treated with the Cox Maze III procedure are free of AF after 1 year. Recent developments in ablation technology have introduced several energy sources capable of creating nonconducting atrial wall lesions. In addition, simplified lesion patterns have been suggested, but results with these techniques have been unsatisfactory. There is a clear need for standardization in AF surgery. The Swedish Arrhythmia Surgery Group, represented by surgeons from all Swedish units for cardiothoracic surgery, has therefore reached a consensus on surgical treatment of concomitant AF. This consensus emphasizes adherence to the lesion pattern in the Cox Maze III procedure and the use of biatrial lesions in nonparoxysmal AF.

Purpose: To explore the effects on atrial and ventricular function of restoring sinus rhythm (SR) after epicardial cryoablation and closure of the left atrial appendage (LAA) in patients with mitral valve disease and atrial fibrillation (AF) undergoing surgery., Methods: Sixty-five patients with permanent AF were randomized to mitral valve surgery combined with left atrial epicardial cryoablation and LAA closure (ABL group, n = 30) or to mitral valve surgery alone (control group, n = 35). Two-dimensional and Doppler echocardiography were performed before and 6 months after surgery., Results: At 6 months, 73% of the patients in the ABL group and 46% of the controls were in SR. Patients in SR at 6 months had a reduction in their left ventricular diastolic diameter while the left ventricular ejection fraction was unchanged. In patients remaining in AF, the left ventricular ejection fraction was lower than at baseline. The left atrial diastolic volume was reduced after surgery, more in patients with SR than AF. In patients in SR, the peak velocity during the atrial contraction and the reservoir function were lower in the ABL group than in the control group., Conclusions: In patients in SR, signs of atrial dysfunction were observed in the ABL but not the control group. Atrial dysfunction may have existed before surgery, but the difference between the groups implies that the cryoablation procedure and/or closure of the LAA might have contributed.

Introduction: We and others have previously shown that antibodies against cyclic citrullinated proteins (anti-CCP) precede the development of rheumatoid arthritis (RA) and in a more recent study we reported that individuals who subsequently developed RA had increased concentrations of several cytokines and chemokines years before the onset of symptoms of joint disease. Here we aimed to evaluate the prevalence and predictive values of anti-CCP antibodies of IgG, IgM and IgA isotype in individuals who subsequently developed RA and also to relate these to cytokines and chemokines, smoking, genetic factors and radiographic score., Methods: A case-control study (1:4 ratio) was nested within the Medical Biobank and the Maternity cohorts of Northern Sweden. Patients with RA were identified from blood donors predating the onset of disease by years. Matched controls were selected randomly from the same registers. IgG, IgA and IgM anti-CCP2 antibodies were determined using EliA anti-CCP assay on ImmunoCAP 250 (Phadia AB, Uppsala, Sweden)., Results: Of 86 patients with RA identified as blood donors prior to the onset of symptoms, samples were available from 71 for analyses. The median (Q1 to Q3) predating time was 2.5 years (1.1 to 5.9 years). The sensitivity of anti-CCP antibodies in the pre-patient samples was 35.2% for IgG, 23.9% for IgA, and 11.8% for IgM. The presence of IgG and IgA anti-CCP antibodies was highly significant compared with controls. IgG and IgA anti-CCP2 predicted RA significantly in conditional logistic regression models odds ratio (OR) = 94.1, 95% confidence interval (CI) 12.7 to 695.4 and OR = 11.1, 95% CI 4.4 to 28.1, respectively, the IgM anti-CCP showed borderline significance OR = 2.5 95% CI 0.9 to 6.3. Concentrations of all anti-CCP isotypes increased the closer to the onset of symptoms the samples were collected with an earlier and higher increase for IgG and IgA compared with IgM anti-CCP. IgA and IgG anti-CCP positive individuals had different patterns of up-regulated chemokines and also, smoking brought forward the appearance of IgA anti-CCP antibodies in pre-RA individuals., Conclusions: Anti-CCP2 antibodies of both the IgG and IgA isotypes pre-dated the onset of RA by years; also, both IgG and IgA anti-CCP2 antibodies predicted the development of RA, with the highest predictive value for IgG anti-CCP2 antibodies.

Non-inferiority trials are questionable when death and serious complications are included among outcomes. The term itself "non-inferiority" is misleading, since such a study would not demonstrate that a new treatment is non-inferior to a control treatment, but simply that the inferiority would not reach a pre-specified level, deemed as acceptable by the designers of the trial. Group cross-over, assay-sensitivity and the need of a placebo arm are major issues for the reliability of non-inferiority trials. The SYNTAX trial for severe coronary artery disease was designed on a non-inferiority margin of 6.6%. In this paper we show that the SYNTAX designers were ready to accept up to 30% higher rate of death and major adverse events to claim the non-inferiority of percutaneous coronary intervention versus coronary artery bypass grafting. Eventually the SYNTAX study failed because percutaneous patients sustained an even higher rate of adverse events. We propose major caution in performing non-inferiority randomized trials.

Objective: The aim of the study was to compare energetic metabolism in the myocardium during coronary surgery with and without cardiopulmonary bypass by means of microdialysis., Methods: Twenty-six low-risk patients were prospectively randomized to off-pump versus on-pump surgery. Microdialysis was used to sample myocardial interstitial fluid during and for 23 hours after surgery., Results: Preoperative characteristics and clinical outcome were similar in both groups. Blood glucose and lactate did not differ between groups throughout the observation time. During surgery, intramyocardial levels of glucose, pyruvate and urea were unaffected in off-pump patients, while the same substances significantly decreased (p<0.05) in on-pump patients during cardioplegic arrest, and increased during reperfusion. Interstitial lactate levels were higher during off-pump surgery (p<0.05). From 3 to 15 hours after surgery, intramyocardial concentrations of glucose, urea and lactate were higher in off-pump patients (p<0.001), while pyruvate was higher in on-pump patients (p<0.01). Intramyocardial lactate/pyruvate ratio never differed between groups. Postoperatively, cumulative blood release of troponin-T was significantly higher in the on-pump group (p<0.005)., Conclusions: Microdialysis could demonstrate significant differences in energetic metabolism between the two groups. Our data confirm and might help in explaining the lower release of myocardial ischemic markers after off-pump surgery., (Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.)

Background: Left ventricular (LV) diastolic function and right atrial (RA) size are not routinely included in preoperative echocardiographic examination in patients undergoing cardiac surgery with concomitant ablation for atrial fibrillation (AF)., Objective: To investigate the role of echocardiographic variables including LV diastolic function and RA area in long-term rhythm outcome prediction, in patients with documented AF undergoing intraoperative ablation concomitant to coronary artery bypass grafting (CABG)., Methods: Thirty-five consecutive patients, scheduled for CABG, and with a history of paroxysmal or permanent AF for 8.5 ± 11.3 years (mean ± SD) (median 5.8 years), were included in this prospective study. Echocardiography was performed prior to and 2.3 ± 0.4 years after the surgical procedure., Results: Both LA and RA areas, LV diastolic function, paroxysmal AF, and sinus rhythm (SR) preoperatively were associated with SR at long-term follow-up. In the multivariate analysis, RA area (P = 0.004), and decreased LV diastolic function preoperatively, measured as the maximal LV long-axis relaxation velocity (P = 0.02), predicted SR at follow-up., Conclusions: RA size and LV diastolic function may be important variables in prediction of long-term rhythm outcome after intraoperative ablation for AF., (© 2010, Wiley Periodicals, Inc.)

Objectives: We sought to assess the clinical and survival benefit of atrial fibrillation surgery in patients submitted to mitral valve surgery after stabilization of postoperative rhythm at 1 year., Methods: One thousand seven hundred twenty-three patients were enrolled. Patients with follow-up of longer than 1 year (n = 972) were divided into 3 groups according to surface electrocardiographic rhythm during follow-up visits: stable sinus rhythm, stable atrial fibrillation, and intermittent rhythms. Adverse cardiac event incidence and predictors of long-term outcome were compared among the 3 groups., Results: In-hospital mortality was 2.6%. Risk factors for mortality were the cut-and-sew technique (odds ratio, 8.92; 95% confidence interval, 1.71-46.50; P = .009) and isolated left atrial procedure (odds ratio, 0.16; 95% confidence interval, 0.04-0.56; P = .004). At 1 year, 63.4% patients were in stable sinus rhythm. Stable sinus rhythm was found to be associated with early and late survival (P = .01, log-rank analysis). Multivariate binary logistic regression analysis found that left atrial dimension (odds ratio, 0.97; 95% confidence interval, 0.96-0.99; P = .005) and concomitant coronary revascularization (odds ratio, 0.48; 95% confidence interval, 0.25-0.92; P = .027) were independent predictors of stable sinus rhythm at 1 year after surgical intervention. At 48 months' follow-up, predictors for stable sinus rhythm were biatrial surgical approach and absence of preoperative permanent atrial fibrillation (odds ratio, 3.56; 95% confidence interval, 1.62-7.83; P < .002). Left atrial size (each millimeter) has a borderline statistical significance (odds ratio, 0.97; 95% confidence interval, 0.93-1.00; P = .065). Thromboembolic events were found to be associated with absence of stable sinus rhythm (P = .010, log-rank analysis)., Conclusions: The achievement of stable sinus rhythm is a predictor of better survival and lower incidence of thromboembolic events. Predictors of stable sinus rhythm were smaller dimensions of the left atrium, biatrial approach, absence of preoperative permanent atrial fibrillation, and absence of concomitant coronary artery bypass grafting.

The aim of this study was to describe life satisfaction prospectively in patients with early rheumatoid arthritis (RA) and to investigate its correlation with disease activity. The early RA group was compared with RA patients with longstanding disease and with a reference group. Gender differences were also compared. Patients with early RA, treated by a multidisciplinary team, reported their life satisfaction by completing a questionnaire. Disease activity score, patient global assessment, and pain were scored at onset of disease and after two years. The patients with early RA were less satisfied with life as a whole at disease onset compared with the reference group, as was a cohort of patients with longstanding disease. Patients with early RA also reported low levels of satisfaction with self-care activities, work, and sexual life. The women reported themselves more satisfied than men. After two years, a slight increase in the reported levels of satisfaction could be seen for life as a whole and for five of the eight domains. No correlation was found between disease activity variables and satisfaction with life as a whole. There were, however, positive correlations between disease activity and satisfaction both with partnership and with family life after two years, i.e. the higher disease activity the higher satisfaction with partnership relation and family life. In contrast, patients with greater disease activity were less satisfied with self-care activities. The results of this study indicate that greater effort is needed to assist patients with early RA to cope with problems concerning self-care activities, sexual life, and work.

Metabolic surveillance of the myocardium is of great interest in cardiac surgery. Microdialysis allows sampling of chemical substances from the interstitial fluid for immediate analysis. The two objectives of this study were to develop a technique for simple and safe implantation of a commercially available microdialysis probe (CMA-70) into the myocardium and to obtain reference data for further use and metabolic control. Eighteen pigs were used in an experimental ischaemic heart model where the left anterior descending coronary artery was occluded for 20 min. Microdialysis was performed proximally as well as distally to the arterial occlusion site corresponding to a control and an ischaemic area in the heart. Two techniques were tried for probe implantation, using either a pacemaker wire attached to the probe tip or a needle introducer. Metabolic substrates (glucose, lactate, glycerol and pyruvate) were collected before, during and after ischaemia, for up to 6 h. Both techniques were highly effective in registering metabolic changes due to ischaemia with sharp time resolution, but the needle introducer was superior regarding probe durability. It is concluded that the CMA-70 microdialysis probe implanted with the needle introducer allows for an accurate monitoring of myocardial metabolism during a prolonged period of time. Future studies in the human heart are warranted to further validate the technique.

Background: Cardiac surgery induces a systemic inflammatory activation and alterations in the hemostatic cascade. The responses contribute to postoperative complications but may also have protective effects. We investigated the relationship between inflammation, hemostasis and bleeding after off-pump coronary artery bypass surgery (OPCAB)., Methods: Ten OPCAB patients were included in a prospective descriptive study. Selected markers of inflammation (IL-6, IL-8, PMN-elastase, C3a, and SC5b-9), and hemostasis (platelet count, ss-thromboglobulin, anti-thrombin, D-dimer and fibrinogen) were measured before and immediately after surgery. Postoperative bleeding was registered., Results: Inflammatory variables did not alter significantly during surgery while ss-thromboglobulin concentrations increased and anti-thrombin and fibrinogen decreased. There were significant postoperative correlations between PMN-elastase and ss-thromboglobulin (r=0.82, p=0.004), between PMN-elastase and fibrinogen (r=0.69, p=0.03) and between C3a and ss-thromboglobulin (r=0.71, p=0.02). In addition, there were significant inverse correlations between postoperative bleeding and pre- and postoperative fibrinogen levels (r=-0.76, p=0.011 and r=-0.84, p=0.002 respectively), between bleeding and postoperative ss-thromboglobulin levels (r=-0.66, p=0.04) and between bleeding and postoperative PMN-elastase (r=-0.75, p=0.01)., Conclusions: The results give further evidence for an association between the inflammatory response and hemostasis after cardiac surgery.

Antibodies against cyclic citrullinated peptide (CCP) and rheumatoid factors (RFs) have been demonstrated to predate the onset of rheumatoid arthritis (RA) by years. A nested case-control study was performed within the Northern Sweden Health and Disease study cohort to analyse the presence of shared epitope (SE) genes, defined as HLA-DRB1*0404 or DRB1*0401, and of anti-CCP antibodies and RFs in individuals who subsequently developed RA. Patients with RA were identified from among blood donors whose samples had been collected years before the onset of symptoms. Controls matched for age, sex, and date of sampling were selected randomly from the same cohort. The SE genes were identified by polymerase chain reaction sequence-specific primers. Anti-CCP2 antibodies and RFs were determined using enzyme immunoassays. Fifty-nine individuals with RA were identified as blood donors, with a median antedating time of 2.0 years (interquartile range 0.9-3.9 years) before presenting with symptoms of RA. The sensitivity for SE as a diagnostic indicator for RA was 60% and the specificity was 64%. The corresponding figures for anti-CCP antibodies were 37% and 98%, and for RFs, 17-42% and 94%, respectively. In a logistic regression analysis, SE (odds ratio [OR] = 2.35), anti-CCP antibodies (OR = 15.9), and IgA-RF (OR = 6.8) significantly predicted RA. In a combination model analysis, anti-CCP antibodies combined with SE had the highest OR (66.8, 95% confidence interval 8.3-539.4) in predicting RA, compared with anti-CCP antibodies without SE (OR = 25.01, 95% confidence interval 2.8-222.2) or SE without anti-CCP antibodies (OR = 1.9, 95% confidence interval 0.9-4.2). This study showed that the presence of anti-CCP antibodies together with SE gene carriage is associated with a very high relative risk for future development of RA.

The interstitial fluid of the human myocardium was monitored in 13 patients undergoing aortic valve and/or bypass surgery before, during, and after hypothermic potassium cardioplegia. The regulation of glucose and lactate was studied after sampling with microdialysis. The following questions were addressed. 1). Is the rate of transcapillary diffusion the limiting step for myocardial uptake of glucose before or after cardioplegia? 2). Does cold potassium cardioplegia induce a critical deprivation of glucose and/or accumulation of lactate in the myocardium? Before cardioplegia, interstitial glucose was approximately 50% of the plasma level (P < 0.001). Interstitial glucose decreased significantly immediately after induction of cardioplegia and remained low (1.25 +/- 0.25 mM) throughout cardioplegia. It was restored to precardioplegic levels 1 h after release of the aortic clamp. Interstitial glucose then decreased again at 25 and 35 h postoperatively to the levels observed during cardioplegia. Interstitial lactate decreased immediately after induction of cardioplegia but returned to basal level during the clamping period. At 25 and 35 h, interstitial lactate was significantly lower than before and during cardioplegia. Glucose transport over the capillary endothelium is considered rate limiting for its uptake in the working heart but not during cold potassium cardioplegia despite the glucose deprivation following perfusion of glucose-free cardioplegic solution. Lactate accumulated during cardioplegia but never reached exceedingly high interstitial levels. We conclude that microdialysis provides information that may be relevant for myocardial protection during open-heart surgery.

Objective: To investigate the time course of troponin-T release into the extracellular fluid of the myocardium and to distinguish between a rise in troponin-T due to implantation trauma and an increase due to cardiac arrest during coronary surgery., Design: Microdialysis probes were implanted in the heart of seven patients soon after sternotomy. Troponin-T was measured in the microdialysates and in peripheral blood from 3 h before to 24 h after heart arrest., Results: The troponin-T concentration in the microdialysates increased immediately after probe implantation and decreased to baseline within 70 min. This early peak is interpreted to reflect a local trauma. Three hours after cross-clamp release, a second peak of microdialysate troponin-T was recorded; 50 times higher than in serum. Eight to 24 h later a third peak occurred in five patients. Serum troponin-T was below the detection level at the beginning of the operation but increased linearly during the first 3 h of reperfusion and remained at that level thereafter., Conclusion: Microdialysis is a safe technique providing more information on myocardial metabolism during and after bypass surgery than can be obtained from peripheral blood. The release of troponin-T in response to cardiac arrest can be distinguished in time from the local tissue response to probe implantation.

The sutureless aortic connector system was recently developed to create anastomoses between the aorta and saphenous vein grafts for coronary artery bypass grafting. Ten consecutive patients scheduled for coronary artery bypass grafting were studied; in each patient one proximal anastomosis was performed using the aortic connector and another was sutured in the conventional manner to serve as the patient's own control. One graft in the sutured group had a significant stenosis and one of the grafts in which the aortic connector was used, was occluded. In this limited study the use of the sutureless connector system for proximal anastomosis shows satisfactory early graft patency (90%).

Background: This study was carried out to establish a mathematical model in order to assess blood trauma and hemorheology during cardiopulmonary bypass and heart valve replacement., Methods: Ten factors which represented blood trauma and hemorheology were investigated in fourteen patients undergoing mechanical heart valve replacement., Results: The results confirmed that red blood cell damage was mainly dependent on cardiopulmonary bypass time and hematocrit level. Platelet aggregation was influenced by platelet count, plasma fibrinogen and cardiopulmonary bypass time, the cases with aortic valve replacement resulting in more platelet activation than the mitral valve replacement (p<0.05). High shear blood viscosity was significantly influenced by hematocrit, plasma viscosity and red cell filterability, while low shear blood viscosity was significantly related to hematocrit, plasma viscosity and fibrinogen concentration, which represented 68.5% and 74.8% of hemorheologic changes due to blood trauma respectively., Conclusions: The relationship between blood trauma and hemorheologic changes was evaluated and the potential areas for improvements in cardiopulmonary bypass techniques in relation to mechanical heart valve implantation were identified. These areas of technical and pharmacological development must reduce changes in all the possible plasma components especially fibrinogen and also preserve platelets and red cells from damage.

From April 1996 to October 1998, 250 patients with a mean age of 63 years (31-86 years) underwent coronary artery bypass grafting using the off-pump technique. The prime reason for using this technique was the need to minimize the surgical trauma by avoiding extracorporeal circulation. Fifty-seven percent of the patients had 1-vessel disease, 39% had 2-vessel disease and 4% 3-vessel disease. Sternotomy was performed in 196 patients and an anterior mini-thoracotomy in 54 patients. The mean number of coronary anastomoses was 1.5. Perioperative mortality was 0.4%. The first consecutive 87 patients underwent an early postoperative coronary angiography (days 1-5) revealing a graft patency of 96.5%. Five out of the 7 patients with occluded grafts subsequently underwent another intervention (surgical revascularization in 4 patients and percutaneous transluminal coronary angioplasty in one); 1.2% developed transmural myocardial infarction and 2.8% were reoperated upon for bleeding. The mean time of ventilatory support was 2.5+/-0.5 h. The mean ICU time for all patients was 12 h (0-10 days). The mean in-hospital time was 7 days (2-30 days). Coronary artery bypass surgery without the use of extracorporeal circulation is a safe procedure that can be performed with limited need for intensive care resources. However, long-term results remain to be investigated.

Recently, new methodology entailing limited anterior thoracotomy or median sternotomy has rendered coronary surgery on the beating heart without extracorporeal circulation safe. Since a program for CABG on beating heart was initiated at Sahlgrenska University Hospital three years ago, 350 operations have been performed, 287 via sternotomy and 63 via limited thoracotomy. Mortality was 1.4% while graft patency in the first 84 patients was 94%. About 20% of all CABG's are performed on a beating heart, and signs are that this percentage is on the rise.

This study aims at developing per- and postopertive surveillance of the myocardium and focuses on ischemic damage following cardioplegic heart arrest. Levels of troponin T and total aspartate aminotransferase (ASAT) were analyzed in the myocardial interstitium of 10 patients with ischemic heart disease (IHD) who underwent coronary bypass surgery and in 12 patients with nonischemic heart disease (N-IHD) who underwent valvular surgery. Fluid from the myocardial interstitium of the anterior and the lateral wall of the heart was sampled by microdialysis probes that were implanted during surgery and extracted percutaneously 70-100 h later. There were no adverse reactions, and the equipment did not interfere with the surgical procedures. The peak in troponin T serum levels that occurred 4 h after cardiac arrest was preceded by a peak in troponin T levels in the microdialysates from the interstitium that occurred 1 h earlier. The concentration of troponin T in the microdialysate peak was 300 times higher than in the serum peak. The increase in serum ASAT levels during the first 7 h after cardiac arrest corresponded in time with a decrease in interstitial ASAT levels, which had already reached a maximum during cardiac arrest. The microdialysate/serum concentration ratio was considerably smaller for ASAT than for troponin T. Interstitial peak levels of troponin T correlated positively and significantly with peak levels of ASAT. Of the 22 patients, 15 had no postoperative events according to clinical outcome, ECG and serum tests. Fourteen of these had low to normal levels of interstitial ASAT and troponin T. Conversely, atrial fibrillation and/or premature atrial contractions were recorded in 8/22 patients, 7 of whom had elevated interstitial ASAT and/or troponin T concentrations in one or both of the sampled heart regions. The N-IHD patients had higher levels of troponin T in the interstitium 20-70 h following cardioplegia, while the peak levels did not differ between the groups. In conclusion, microdialysis sampling of troponin T and ASAT is safe and allows a highly sensitive analysis of the ischemic trauma exerted by the cardioplegic arrest., (Copyright 2000 S. Karger AG, Basel)

Extracellular levels of amino acids in the myocardial interstitium are sensitive indicators of myocyte function. Lowered ATP leads to a rapid extracellular appearance of amino acids with a high intra- to extracellular concentration ratio, such as taurine and glutamate. Nitrogen fluxes are reflected by glutamine, while alanine, glycine, serine and leucine are markers of proteolysis. In addition, degradation of membrane phospholipids is reflected by other primary amines, such as phosphoethanolamine. The time course of these changes was determined before, during and after cardioplegic heart arrest. Two regions of the heart were monitored in 20 patients by means of microdialysis sampling. After only 20 min of heart arrest, extracellular taurine, glutamate and phosphoethanolamine increased transiently up to 25 times the basal level. Ten-20 min later, glutamine increased by 6 times. A doubling of alanine, glycine, serine and leucine levels took place 30 min after release of the aortic cross-clamp. After 2 h, all were at levels similar to those recorded 15-30 h later. Levels of taurine and glutamate in the anterior wall of the heart correlated significantly with those of its lateral wall. The response to surgery and heart arrest was studied in a group of patients with ischemic heart disease as well as in another group of patients, who underwent heart surgery for nonischemic reasons. The response of taurine and glutamine was significantly higher for the patients with ischemic heart disease, in spite of a shorter mean time of heart arrest. No sex differences were recorded. High levels of amino acids coincided frequently with clinical events, which were suggestive of ischemia, but were also recorded in a few patients without diagnosed events. We conclude that monitoring of extracellular amino acids is valuable for evaluation and development of cardioprotective strategies.

Objective: To investigate haemorheological changes in patients undergoing coronary artery bypass grafting and to determine whether the protective effect on haemorheology of high-dose aprotinin also exists under a half-dose regimen., Methods: Forty patients were studied in a double-blind, placebo-controlled study design. Patients in the aprotinin group received half of the standard high dose of aprotinin during surgery. Erythrocyte and white-cell clogging rates as well as whole blood and plasma viscosity were measured. Viscosity results were expressed as a ratio to the viscosity of saline., Results: Erythrocyte and white-cell clogging rates were increased significantly, whereas whole blood and plasma viscosity were decreased significantly during cardiopulmonary bypass. The reduction in viscosity had a strong correlation to haemodilution. There was no significant difference in any of the measured variables between the aprotinin and the placebo groups., Conclusion: This study showed that blood cell damage occurred during cardiopulmonary bypass surgery, as measured by a raised clogging rate. This tendency was the same in both groups and therefore no increased potential for microthrombi could be attributed to aprotinin haemorheologically. However, half-dose aprotinin did not show any preserving effect in haemorheology when the blood-cell clogging rate and blood viscosity were studied.

Objective: To evaluate retrospectively our surgical experience, techniques and long-term results in 11 patients with coronary artery fistulae associated with other cardiovascular anomalies., Methods: From January 1980 to April 1995, 11 patients with coronary artery fistulae associated with other cardiovascular anomalies were found among 20,000 open-heart procedures and treated surgically. Besides closure of the fistulae, coronary artery bypass grafting was performed in 5 patients with atherosclerotic coronary artery disease, and aneurysm angioplasty was done in 4 patients with coronary artery aneurysm. Ventricular septal defect and patent ductus arteriosus were closed in one patient and mitral valve replacement was performed in another patient., Results: There were no surgical deaths, but one late death due to acute myocardial infarction occurred 6 months after surgery. The mean follow-up time was 75.7 months and all patients' functional status improved by an average 1.4 judged by the New York Heart Association functional classification., Conclusions: Coronary artery fistula associated with other cardiovascular anomalies will aggravate symptoms and cause deterioration of heart function. Therefore, evaluation and surgical intervention should be done as soon as possible to restore coronary blood flow and correct concomitant cardiovascular anomalies. The surgical results are excellent with a low operative risk and good long-term results.

The predominant causes of late graft loss and death after cardiac transplantation are graft rejection and infection. The histopathological classification of acute rejection is based on cellular phenomena such as lymphocytic infiltration and myocyte damage. The adverse prognostic importance of vascular or humoral rejection has been reported, but there is no well-documented treatment available. In our experience, comprising 151 orthotopic transplants, five patients presented with graft rejection characterized by a lymphocytic vasculitis that did not respond to conventional therapy. Because of a deteriorating condition, in spite of vigorous antirejection treatment that included inotropic drugs and circulatory support. plasmapheresis was tried as a last, desperate means to stop the process from developing further. The clinical symptoms rapidly subsided in all five patients after the first couple of plasma exchanges. All of the patients are alive and well after 2-3.5 years of follow-up. Although the mechanism of action is unclear, plasmapheresis was beneficial in these critically ill patients.

The purpose of this study was to evaluate the cardiac damage by cardiac myosin light chain I after transplantation. This study included 30 patients who underwent cardiac operations and who were divided into three groups. These groups consisted of (1) control group, 15 valvular patients without coronary disease (no electrocardiography changes and creatine kinase MB isoenzyme of 100 micrograms/L or less); (2) infarction group, eight patients (six coronary bypass and two valvular patients with perioperative infarction pattern in the electrocardiography and creatine kinase MB isoenzyme of 100 micrograms/L or more; and (3) transplantation group, seven transplant patients (six heart and one heart-lung). The peak cardiac myosin light chain I value in the transplantation group (32.9 +/- 3.4 micrograms/L) was comparable to the infarction group (27.6 +/- 2.6 micrograms/L), and both of them were significantly higher than the control group (9.2 +/- 0.9 micrograms/L) (p < 0.01). Peak cardiac myosin light chain I levels in the control and transplantation groups correlated with the ischemic time (r = 0.48, p < 0.05 and r = 0.67, p < 0.05, respectively). The total dose of dopamine in the transplantation group correlated with the peak cardiac myosin light chain I (r = 0.67, p < 0.05), and with the cardiac myosin light chain I value on day 7 (r = 0.88, p < 0.01). This study suggests that circulating cardiac myosin light chain I estimations are useful to evaluate myocardial damage after transplantation during postoperative week 1.

Sudden mediastinal haemorrhage one month after heart transplantation in an 18-year-old youth was found to originate from a rupture of the ascending aorta associated with mycotic aortitis. Aortic continuity was restored with a Dacron graft. Cultures from the resected vessel wall showed Candida albicans. The patient recovered, and 11 months later is well.

The incidence of chordal tissue in endomyocardial biopsies from heart transplant recipients and the possibility of an association between this incidence and tricuspid regurgitation or tricuspid valvular abnormalities were prospectively investigated. The biopsies were performed to detect rejection. Postoperative echocardiography and Doppler were done according to routine schedule and always when chordal tissue was found histologically, for specific evaluation of the tricuspid valve function. Chordal tissue was detected in 24 of 1,265 bites at 206 biopsies during the study period. Echocardiographically there was no significant increase in tricuspid regurgitation and no major valvular abnormality in any patient after biopsy showing chordal tissue. The presence of chordal tissue in biopsy specimens implies that the tricuspid valve is potentially at risk in biopsy. Our results, however, also showed that occasional capture of chordal tissue by the bioptome did not necessarily result in tricuspid valve dysfunction.

Heart transplantation is well established therapy for end-stage heart failure, where no other treatment is available. From 1983 to the end of 1993, 620 heart transplantations were performed in the Nordic countries, the main causes of heart failure being dilated cardiomyopathy and ischaemic heart disease. The 1-year and 5-year actuarial survival rates were above 80 per cent and 70 per cent, respectively, which are higher than corresponding figures reported by the International Society of Heart and Lung Transplantation. The indications and contra-indications for heart transplantation, pre-operative evaluation and outcome are discussed in the article.

The limiting factor in organ transplantation is the availability of organs. Continuing work to improve the public's willingness to donate organs and inspire hospital staff to collaborate in organ procurement is essential. Identification of patients who will not benefit from transplantation can also increase the availability of organs. Grafts may also be saved by identification and appropriate treatment of recurrent renal disease. Xenotransplantation may eventually solve the problem, but major obstacles remain. Meanwhile, work in this field may help to clarify mechanisms of rejection. New immunosuppressive drugs may improve graft survival and reduce the incidence and progression of chronic rejection.

The morbidity of cytomegalovirus (CMV) infection and toxoplasmosis was evaluated in 75 heart transplant recipients. Among the 73 patients who survived more than one week after transplantation, 16 (22%) acquired primary CMV infection and 30 (41%) had evidence of secondary infection. All CMV seronegative recipients receiving hearts from seropositive donors developed CMV infection. The majority of infections (42/46) occurred during the first 4 months after transplantation. Overall, the incidence of symptomatic CMV disease was 44%. The infections were generally mild and only 1 death was attributed to primary CMV disease complicated by bacterial septicaemia and multiple organ failure. The severity of CMV disease was greatest among those with primary infection. There were 3 cases of toxoplasmosis. Two patients were toxoplasma seronegative before transplantation and developed clinical and serological signs of infection 2-3 months after transplantation despite receiving organs from seronegative donors. Of toxoplasma seronegative recipients receiving allografts from seropositive donors 3/4 were prophylactically treated with pyrimethamine for 6 weeks. None developed clinical or serological signs of toxoplasmosis while one patient who received trimethoprim-sulfamethoxazole had a subclinical infection.

The purpose of this study was to investigate the occurrence of major tricuspid insufficiency caused by endomyocardial biopsy in heart transplant recipients. Endomyocardial biopsy was used for the detection of rejection and Doppler echocardiography was performed at regular intervals. Six of 96 heart transplant patients (6.3%) had sudden appearance of large tricuspid regurgitation, all of which were directly related to a preceding biopsy. Chordal tissue was identified histologically in biopsy samples of all six patients. All patients developed symptoms of right ventricular failure which was confirmed by right heart catheterization. Three patients subsequently underwent valvuloplasty for ruptured chordae tendineae of either of the three leaflets. Two of these three patients were free from symptoms during follow-up, but the third patient developed moderate tricuspid regurgitation and clinical symptoms. It is concluded that endomyocardial biopsy, although it is the most useful tool for detection of rejection, should be used with caution with regard to anatomical structures and the risk of damage to the tricuspid valve must not be neglected. It is also concluded that valvuloplasty of the tricuspid valve can be successfully performed in a transplanted heart.

A positive effect on survival of renal grafts of pretransplant blood transfusions have been reported from several centers. The aim of this study was to study if the described graft-protecting effect of blood transfusion was present in the Gothenburg material of transplanted patients, and if this effect could be achieved by deliberately transfusing previously non-transfused patients with two units of leukocyte-reduced blood. The effect on graft survival (GS) of the number and timing of transfusions to recipients, transfusions to the cadaveric donors, HLA-A, B matching, lymphocytotoxic antibodies and pretransplant hemodialysis was also studied. The study includes 844 recipients of primary renal grafts from living related and cadaveric donors (LRD, CD) and 70 patients waiting for transplantation. In the retrospective part of the study the GS of previously transfused and non-transfused non-transfused patients was compared. In the prospective part of the study a protocol with two deliberate transfusions (DT) to previously non-transfused patients was introduced. The GS of the DT group was compared to that for patients transfused for strictly medical reasons (MT) and non-transfused patients (NT). Survival of patients and grafts was calculated according to the life table method. In the retrospective part of study one year GS in LRD transplantation was 86.6% for transfused and 38.4% for non-transfused patients (P less than 0.01). In the first period one year GS in CD transplantation was 62.1% for transfused and 35.1% for non-transfused patients (P less than 0.01). The corresponding figures in the second period were 68.1% and 39.5%, respectively (P less than 0.001). In transfused recipients receiving kidneys from transfused and non-transfused cadaveric donors, the GS was 76.3% and 55.4%, respectively (P less than 0.05). In the prospective part of study the one year GS after LRD transplantation was 85.0% in both the DT and MT groups. In CD transplantation the one year GS was 73.4% and 75.7% of the DT and MT groups, respectively. The GS of each of these two groups was significantly better than that of 20.8% for the NT group (P less than 0.01). Lymphocytotoxic antibodies were detected in 5.0% of the DT group and 23.0% of the MT group (P less than 0.001). Foreign HLA-B series antigens had a negative influence on GS in the first period of the retrospective CD study. Later, no influence on GS was noted of HLA-A, B matching. Hemodialysis prior to transplantation did not influence GS.(ABSTRACT TRUNCATED AT 400 WORDS)