Objective: We present real world experience from a single center registry comparing the 6-month outcome of percutaneous coronary intervention (PCI) in unselected high-risk individuals using either sirolimus-eluting (SES) or paclitaxel-eluting stents (PES). Methods/Results: We compared clinical outcome at 6 months follow-up in two cohorts of 156 consecutive patients(total n = 312) who underwent SES (June 2002-Februrary 2003) and PES(march 2003-July 2003) implantation. The primary endpoint was a composite of major adverse cardiac events (MACE). Baseline clinical characteristics were well matched. The 6-month target vessel revascularization (TVR) rates were 1.9% (SES) and 2.6% (PES) and MACE rates were similar in the two groups (SES 4.5% vs. PES 3.2%, P = NS). In the PES group, intervention for multivessel disease, bifurcation lesions and in small vessels was more common, and for in-stent restenosis less common, reflecting the impact of drug eluting stents on indications for PCI. The incidence of sub-acute stent thrombosis, related to inadequate antiplatelet therapy in 3 of the 6 cases, was 0.95% with no difference between the two groups. Conclusion: This study confirms the safety and efficacy of SES and PES in unselected high risk patients undergoing PCI. Clinical outcomes of both stents are equivalent at 6 months with low rates of MACE and TVR. These data provide important complementary information to forthcoming randomized studies. (C) 2006 Wiley-Liss., Inc.

Aims: Interleukin-(IL-) 6 is a pleiotropic cytokine with effects on the acute phase response, inflammation, and vascular function. A G to C polymorphism has been described at position - 174 in the promoter region of the IL-6 gene. We investigated the influence of this polymorphism on the development of cardiac transplant related coronary vasculopathy (CV).Methods: Sequence specific polymerase chain reaction identified the -174*G/C allele for 116 cardiac transplant recipients. Coronary disease was identified by routine surveillance post-transplant coronary angiography.Results: Prevalence of the - 174*G/C polymorphism was different between the transplant and control cohorts; *CC 27.6%, *CG 45.7%, and *GG 26.7% vs. 13.2%, 44.1% and 42.7% respectively (P = 0.004). Median time to the first diagnosis of CV was different between the 3 alleles; *CC 2.8 years (2.0-4.0); *CG 3.9 years (2.1-4-5); *GG 5.3 years (3.2-6.1) (1) = 0.05). By Kaplan-Meier survival analysis C homozygotes developed CV significantly earlier than the other cohorts (1) = 0.035). At 5 years 100% of C homozygotes had evidence for CV. G homozygotes had a more gradual onset of CV with an approximate 60% prevalence at 5 years. *CC genotype was the most predictive risk factor for CV development (Hazard ratio 4.2 (95% CI 1.3-12.9); p = 0.014). Increasing donor age was also significant (Hazard ratio 1.04 (95% CI, 1.0-1.08); p = 0.023).Conclusions: Polymorphism at position - 174 within the promoter region of the IL-6 gene may be an important risk factor for cardiac transplant related coronary vasculopathy. This may improve patient selection and allow tailored immunosuppressive treatment. J Heart Lung Transplant 2005;24:559-65. Copyright (c) 2005 by the International Society for Heart and Lung Transplantation.

A 61 year old patient was found to have an aneurysm extending from the aortic root to the suprarenal region. He underwent first stage surgery with aortic root and arch replacement, prosthetic aortic valve replacement, and coronary artery bypass grafting. Four weeks later, he presented with breathlessness and signs of heart failure and pleural effusion. Computed tomography showed that the left atrium was compressed between the aortic aneurysm posteriorly and the left ventricle and sternum anteriorly. Obstruction of the superior vena cava, bronchus, oesophagus, and rarely right atrium by an aortic aneurysm has been described before but presentation with left atrial compression has not been reported.

A 45 year old man who had previously undergone curative surgery and radiotherapy for a thoracic neuroblastoma in childhood was referred for assessment of breathlessness and exertional dizziness. A high resolution thoracic computed tomographic scan demonstrated patchy pulmonary fibrosis and incidentally revealed the presence of localised extensive calcification throughout the left atrium …

BACKGROUND:Coronary vasculopathy (CV) is an important determinant of survival following cardiac transplantation. We have previously shown that G915C polymorphism of the Transforming Growth Factor-beta1 (TGF-beta1) gene strongly influences CV development. Furin is a proprotein convertase enzyme important in TGF-beta1 activation. We investigated for polymorphism within the promoter region of the gene for furin (fur). Allelic variation of the fur gene, in conjunction with TGF-beta1 polymorphism, was subsequently related to the development of CV. METHODS AND RESULTS:The fur gene promoter region (position -1199 to +39) was analysed by SSCP and sequencing. A C/T single nucleotide substitution polymorphism at position -231* was identified. Using PCR the fur and TGFB1 genotypes were identified in 115 cardiac transplant recipients. CV was diagnosed at routine surveillance post-transplant coronary angiography. Fur polymorphism had no influence on vasculopathy development; median time to diagnosis, *C/C homozygotes, 2.27 years (2.10-4.32), *C/T heterozygotes 2.97 years (2.09-4.24), *T/T homozygotes 2.65 years (2.33-4.08), (P=0.95). Allelic variation did not influence Kaplan Meier actuarial analysis of disease onset (P=0.54). Ninety-three percent of recipients were high TGF-beta1 producers. We used fur polymorphism to substratify patients with the +915*G/G TGFB1 (high producing) allele. Fur polymorphism did not influence CV development within this TGF-beta1 high producer cohort, when analysed by time to first diagnosis and Kaplan Meier testing. CONCLUSIONS:We have described a novel polymorphism at position -231* in the gene encoding furin. The fur -231* single nucleotide polymorphism in isolation, or in conjunction with TGFB1 polymorphism, is not useful as a genetic risk marker for cardiac transplant associated coronary vasculopathy.

OBJECTIVES:The purpose of this study was to investigate the association between haptoglobin phenotypic variation and development of cardiac transplant vasculopathy. BACKGROUND:The development of coronary vasculopathy determines long-term survival after cardiac transplantation. Serum haptoglobin levels are associated with non-transplant atherosclerosis. In addition to free hemoglobin binding, haptoglobin influences free radical formation, prostaglandin synthesis and angiogenesis. Three phenotypes of haptoglobin exist in humans, which have both quantitative and qualitative differences. METHODS:Coronary disease was diagnosed at post-transplant routine surveillance angiography. Hemoglobin (10%) was added to recipient plasma to form a haptoglobin-hemoglobin complex. Sample aliquots were applied to acid hemoglobin plates and electrophoretically separated. Phenotypes were recognized by comparing the electrophoretic pattern with that of established standards. Haptoglobin concentrations were measured using an immunoturbidimetric technique with polyethylene glycol (PEG)-enhanced precipitation. RESULTS:Ninety-three patients were independently studied. Phenotype 1-1 was found in 20.4%, 2-1 in 41.9% and 2-2 in 37.6%. Haptoglobin levels were highest in 1-1 recipients (2.1 +/- 0.58 g/liter) compared with 1.78 +/- 0.88 g/liter and 1.3 +/- 0.81 g/liter in 2-1 and 2-2 individuals, respectively (p = 0.001). Haptoglobin phenotype was significantly related to the development of vasculopathy; recipients with a 2-1 phenotype were more likely to develop angiographic disease (p = 0.0084). No differences were found among the 3 groups according to univariate analysis. Multivariate analysis identified 3 risk factors for vasculopathy development: age of donor (hazard ratio 1.056 [95% confidence interval 1.02 to 1.094], p = 0.0023); pre-transplant recipient body mass index (hazard ratio 1.116 [95% confidence interval 1.015 to 1.23], p = 0.024), and haptoglobin phenotype (hazard ratio 2.725 [95% confidence interval 1.031 to 7.19], p = 0.012). CONCLUSIONS:Haptoglobin, through phenotype-dependent mechanisms, correlates with the development of coronary vasculopathy. This finding furthers our understanding of the disease, opens up new areas of research, and may lead to novel therapies.

Background: Transforming growth factor-beta1 (TGF-beta1) has been implicated in the pathogenesis of coronary vasculopathy following cardiac transplantation. The TGFBI gene contains polymorphisins at positions +915* (Arg25Pro) and +869* (Leu10Pro) which may influence TGF-beta1 expression. We investigated the relationship between the development of coronary vasculopathy and the prevalence of these alleles in a cardiac transplant population.Methods: Vasculopathy was diagnosed at routine surveillance post-transplant coronary angiography. Using sequence-specific polymerase chain reaction we identified the TGFB1 +915* and +869* genotypes in 147 cardiac transplant recipients and 134 cardiac donors.Results: TGFbeta1 +915*C allele carriers (low producers) made up 10.5% of the recipient population but were significantly less likely to develop coronary vasculopathy (P = 0.03). Median time to diagnosis was 6.0 years (3.9-8.72) in +915*C allele carriers compared to 2.75 years (2.10-4.22) in *G/G homozygotes (p = 0.002). Pre- and I year post-transplant clinical variables were equivalent between the two groups. Multivariate analysis identified the recipient +915*G/G genotype (hazard ratio 2.96 (95% CI, 1.09-9.98); p = 0.039), donor age (hazard ratio 1.05 (95% CI, 1.02-1.09); p = 0.008) and number of acute rejection episodes of ISHLT grade 3 or greater in the first year (hazard ratio 1.12 (95% CI, 1.01-1.23); p = 0.03) as significant predictors of vasculopathy. The recipient TGFBI +869*, and both alleles in the donor, had no influence on vasculopathy development.Conclusions: Recipient TGFBI +915* genotype influences the development of cardiac transplant-related coronary vasculopathy. This gives an important insight to the pathophysiology of the disease. On the contrary, donor TGFBI +915* and TGFBI +869* polymorphisms do not appear to be important and cannot be used as genetic risk factors. (C) 2004 Elsevier B.V. All rights reserved.

Background: Interleukin-10 (IL-10), an important anti-inflammatory cytokine has been implicated in the pathogenesis of acute rejection and long term graft tolerance. Polymorphism in the IL-10 promoter at positions −1082, −819 and −592, correlates with IL-10 production. Haplotype inheritance of these alleles determines whether individuals are high, intermediate, or low producers of IL-10. We investigated the effect of this polymorphism on the development of cardiac transplant vasculopathy (CV). Methods: CV was defined at routine surveillance coronary angiography as any abnormality in 1 or more epicardial vessels. Recipient and donor DNA was amplified by PCR using primers to the 3 allele sites. After identifying the phenotype by electrophoresis, freedom from CV was analysed by Kaplan–Meier and the log rank test. Results: One hundred and forty eight recipients and 135 donors were studied. High, intermediate and low producers made up 26.4, 47.3 and 26.3% of recipients and 35.6, 48.2 and 16.2% of donors (P=0.42). No significant differences were noted between the phenotype groups. The recipient and donor genotypes, when considered in isolation, had no effect on the freedom from CV; recipients: P=0.85; donors: P=0.52. When the recipient and donor genotypes were combined for an individual patient the freedom from CV was again unaffected; high producing IL-10 allele in donor or recipient: P=0.76, low producing IL-10 allele in donor or recipient: P=0.51. Increasing donor age and acute rejection episodes and the presence of a high producing TGF-β1 phenotype were independent risk factors for CV. Conclusions: Polymorphism of the IL-10 promoter region fails to predict the development of CV and cannot be used as a genetic risk marker. This may be due to the effects of immunosuppressive treatment.

PURPOSE: C-reactive protein is an important risk factor for coronary artery disease, and plasma concentrations are lowered by treatment with pravastatin and aspirin. We examined whether other cardiovascular drugs that are used in the treatment of ischemic heart disease affect C-reactive protein concentrations.SUBJECTS AND METHODS: Plasma C-reactive protein concentration was measured by high sensitivity immunonephelometric assay in 333 consecutive patients with stable angina and confirmed coronary artery disease who underwent diagnostic angiography.RESULTS: Patients prescribed beta-blockers had significantly lower mean C-reactive protein concentrations than did patients in whom these were not prescribed (by 1.2 mg/L, or 40% difference in geometric mean concentration; P <0.001). This association remained significant (P = 0.03) after excluding patients with contraindications to the use of beta-blockers, and adjusting for the probability of beta-blocker therapy (propensity score) and other clinical predictors of C-reactive protein concentration, including body mass index, high-density lipoprotein cholesterol level, family history of coronary artery disease, and angiographic severity. No differences among types or dosages of beta-blockers were evident.CONCLUSION: Beta-blockers may affect C-reactive protein concentrations. Randomized studies are required to confirm these findings. (C)2002 by Excerpta Medica, Inc.