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Left dominant arrhythmogenic cardiomyopathy (LDAC) exhibits characteristic phenotypic and genetic features which were found in the five Spanish family members described in this study. Triggered by a cold, a young man presented with a ventricular tachycardia of left ventricular origin and left ventricular late gadolinium enhancement. His resting ECG showed low potentials, delayed ventricular depolarization (inferior and V4-V6 leads) and atrioventricular conduction disturbances. His endomyocardial biopsy revealed myocyte loss with interstitial fibrosis. Despite the initial diagnosis of myocarditis, familial screening was pivotal in confirming the diagnosis of LDAC. A novel nonsense mutation in the desmoplakin gene (Q1866X) and the truncated protein which it produces were observed in skin samples., (Copyright © 2010 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.)

Introduction: One of the most common, significant problems after heart transplantation (HT) is the development of renal dysfunction. In recent years, the glomerular filtration rate (GFR) has replaced the serum creatinine as the standard parameter for its determination. Our objective was to analyze which renal function parameter (creatinine or GFR) at 1 year after HT better classified patients who will die during follow-up., Patients and Methods: The study included 316 consecutive HT patients surviving at least 1 year after transplantation. Creatinine and GFR were determined by the Modification of Diet in Renal Disease Study (MDRD4) equation. Mortality during the follow-up was analyzed to compare both parameters using receiver operating characteristic curves., Results: Over a mean follow-up of 6±3 years, 97 patients died (30.7%). At 1 year after HT, the patients who succumbed displayed a significantly higher mean creatinine value (1.63±0.65 vs 1.41±0.64 mg/dL; P=.004) and a more decreased GFR (53.8 vs 60.8 mL/min/1.73 m2; P=.006). Both groups had the same area under the curve, 0.61 (95% confidence interval: 0.54-0.68; P=.002)., Conclusion: Among our population, GFR calculated by the abbreviated MDRD4 equation did not provide any additional prognostic value to serum creatinine at 1 year after HT to predict long-term mortality., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Introduction and Objectives: The development of renal failure is one of the most important problems after heart transplantation (HT), but the wide range of definitions means that estimates of its prevalence vary considerably. Furthermore, its impact on mortality has not been adequately studied. The objective was to investigate the relationship between the glomerular filtration rate (GFR) 1 year after transplantation and mortality during follow-up., Methods: The GFR was determined in 316 patients still living 1 year after transplantation using the abbreviated Modification of Diet in Renal Disease Study formula. Patients were divided into three groups according to GFR (i.e. <30, 30-59 and > or =60 mL/min per 1.73 m2) and pretransplant variables and rejection and infection rates within the first year were analyzed. The association between GFR at 1 year and mortality during follow-up was evaluated and reasons for the association were examined., Results: There was no difference in the number of rejections or infections in the first year between the three groups. During a mean follow-up period of 6.3 years, 74% of patients with a GFR <30 mL/min per 1.73 m2 died, compared with 24% and 30% of those with a GFR > or =60 and 30-59 mL/min per 1.73 m2, respectively. Survival analysis (i.e. Cox regression analysis) demonstrated a significant difference between patients with a GFR <30 mL/min per 1.73 m2 and other patients (P< .001). A very low GFR at 1 year was the only independent predictor that remained statistically significant on multivariate analysis (hazard ratio =2.87; 95% confidence interval, 1.52-5.41)., Conclusions: Severe renal dysfunction at 1 year was an independent predictor of long-term all-cause mortality in heart transplant patients.

Diaphragmatic involvement by an endometriotic cyst is a rare entity that may be responsible for chronic thoracic pain. Herein we present a case report of a 6-cm right diaphragmatic endometrioma treated using laparoscopic partial excision and argon laser coagulation of the inner cyst wall. The laparoscopic approach to upper abdomen endometriosis is feasible and safe when accurate evaluation of the case is performed., (Copyright (c) 2010 AAGL. Published by Elsevier Inc. All rights reserved.)

Protein-losing enteropathy is a rare but life-threatening complication that occurs in some patients who develop intestinal lymphangiectasis secondary to increased systemic venous pressure. Although different forms of treatment have been tried, with varying results, the majority were reported to be unsuccessful. The aim of this study was to demonstrate that heart transplantation may be an appropriate therapeutic option for patients who do not respond to medical treatment. At our center, we performed heart transplantations in three patients with this condition. The mean follow-up period was 11+/-2 months. No patient died and the enteropathy regressed in all three.

Although the control of thrombin in the microvasculature at the endothelial cell surface is crucial to prevent atherothrombosis, the role of antithrombin in arterial thrombosis is unclear. It is widely considered that antithrombin deficiency is unlikely to contribute to arterial thrombosis, but no convincing epidemiological study has been performed because of the low frequency of this deficiency. In this study we evaluated the role in myocardial infarction (MI) of a relatively common mutation affecting antithrombin gene (A384S: Antithrombin Cambridge II) that has functional features that may impair the right control of thrombogenic events caused by injury to the vascular wall. Moreover, this deficiency, which is not detected using common methods to diagnose antithrombin deficiency, also increases the risk of venous thrombosis. We included 1,224 patients with MI (691 consecutive patients and 533 survivors of a premature event), and 1,649 controls. The mutation was identified in 0.3% of controls, but 0.8% of MI patients. After adjusting for sex and other cardiovascular risk factors, the antithrombin Cambridge II significantly increased 5.66-fold the risk of MI (95% CI: 1.53-20.88; p = 0.009). Interestingly, young patients had the highest risk of MI associated with the mutation (OR: 9.98; 95%CI: 1.60-62.24; p = 0.009). This is the first epidemiological study that supports a role for antithrombin deficiency in arterial thrombosis. These results suggest that deficiency of antithrombin may be an independent risk factor for MI that has been underestimated, but larger studies are needed to confirm the relevance of inhibitors of thrombin in arterial thrombosis.

microRNAs have recently opened new pathways to explain gene expression and disease biology in many scenarios, including cardiac diseases. microRNAs are endogenous small non-coding RNAs that mediate post-transcriptional repression or messenger RNA degradation. By annealing to inexactly complementary sequences in the 3' untranslated region of the target messenger RNA, protein level is down-regulated. Several microRNAs appear to act cooperatively through multiple target sites in one gene and, conversely, most microRNAs can target several genes. miR-133 and miR-1 are specifically expressed in cardiac and skeletal muscle and control myogenesis, cardiac development, cardiac performance and cardiomyocyte hypertrophy (mainly by tuning transcription factors and other growth-related targets). They also modulate the expression of certain cardiac ion channels and related proteins with proarrhythmic effect. Besides them, other microRNAs have been shown to exert influence on the myocardial growth, the electrical balance and the angiogenesis processes that take place in the heart. Bioinformatics is a useful tool to identify potential targets of a given microRNA, although there is still substantial concern about their reliability. Experimental manipulation of microRNAs has provided a tantalizing basis to speculate that future research on microRNAs may yield important progress in the prevention of sudden cardiac death and in the treatment of cardiac heart failure. However, the final effect of the blockage of microRNAs in vivo remains unclear, since each of them can target hundreds of genes with different intensity. The era of the microRNAs in cardiovascular diseases has just started.

Background: Inflammatory reactions contribute to the development of arterial disease. We investigated the role of interleukin-4 (IL-4) in the development of myocardial infarction (MI) by genotyping patients with MI and control subjects for the -589C>T (rs2243250) single nucleotide polymorphism (SNP), which tags a functional haplotype of IL-4., Methods and Results: Study of Myocardial Infarctions Leiden (SMILE) included 560 men with a first MI and 646 control subjects. The Valencia study included 305 patients with MI at T genotype was found [odds ratio (OR) 0.84; 95% CI 0.37-1.95 for -589TT and 0.82; 95% CI 0.62-1.07 for -589CT compared with -589CC]. In patients younger than 50 years, carriership of one or two -589T alleles was associated with a reduced risk of MI (OR 0.57: 95% CI 0.34-0.95). This result was replicated in the Valencia study, where carriers of one or two -589T alleles had a reduced risk of MI (OR 0.67: 95% CI 0.47-0.95), with a strong protective effect of the -598T allele in homozygous -589T (OR 0.33: 95% CI 0.10-1.05). In the control subjects of the Valencia study, the -589T allele was associated with reduced levels of F1+2., Conclusion: Our data indicate that the IL-4 haplotype tagged by the -589T allele reduces the risk of MI in young individuals.

Background: Haplotypes A1 and A3 in the endothelial protein C receptor gene are tagged by the 4678G/C and 4600A/G polymorphisms, respectively, and have been reported to influence the risk of venous thromboembolism. We assessed whether these haplotypes modify the risk of premature myocardial infarction., Design and Methods: We genotyped these polymorphisms in 689 patients with premature myocardial infarction and 697 control subjects. Activated protein C and soluble endothelial protein C receptor levels were also measured., Results: After adjustment for other cardiovascular risk factors, A1 and A3 haplotypes protected against premature myocardial infarction (odds ratio 0.7, 95% CI 0.4-0.8, p=0.044 and 0.5, 0.3-0.6, p<0.001, respectively). Moreover, the protective role of these haplotypes seemed to be additive, as carriers of both the A1 and A3 haplotypes had adjusted odds ratios of 0.3 (0.2-0.5, p<0.001) and 0.4 (0.2-0.8, p=0.006) compared to those carrying only the A1 or A3 haplotype, respectively. The presence of the A1 haplotype was associated with increased levels of activated protein C whereas individuals carrying the A3 haplotype showed the highest soluble endothelial protein C receptor levels., Conclusions: These results show that A1 haplotype carriers have a reduced risk of premature myocardial infarction via the association of this haplotype with increased activated protein C plasma levels. The study also shows that carriers of the A3 haplotype have a reduced risk of myocardial infarction, only in part due to increased soluble endothelial protein C levels.

The role played by hemorheological alterations on acute myocardial infarction (AMI) in young patients remains a question of debate. We have carried out a case-control study of 84 AMI patients aged <45 years and 135 sex and age matched controls, in which blood viscosity (BV), plasma viscosity (PV), erythrocyte aggregation (EA) performed with the Myrenne (EA0, EA1) and the Sefam aggregometer (Ta, AI10, gammaD), erythrocyte deformability (ED) along with fibrinogen (Fbg), C-reactive protein (CRP) and plasmatic lipids i.e. total cholesterol (T-Chol) and triglycerides (TG) were determined. AMI patients showed higher, Fbg, TG, EA0, EA1, IA10, gammaD and lower Ta than controls (p=0.029, p<0.001, p=0.013, p=0.003, p=0.010, p=0.025) respectively. No differences in the other rheological parameters were observed. No differences in any rheological parameter were observed regarding the AMI type, number and score of stenosed vessels and the time elapsed since the thrombotic event. After multivariate adjustment, Fbg>380 ml/dl and TG>185 ml/dl were independently associated with a higher risk of erythrocyte hyperaggregability (OR: 5.5 CI 95% 1.04-29.27 and OR: 7.3 CI 95% 2.66-20.03) respectively. EA>8.85 was associated with a increased AMI risk (OR: 5.3 CI 95% 1.98-14.5). These results reinforces the view that in young AMI patients increased Fbg and TG may promote the development of ischaemic events not only through its known mechanism but also by altering rheological blood behaviour, mainly increasing EA.

The fibrinolytic system includes a broad spectrum of proteolytic enzymes with physiological and pathophysiological functions in several processes, such as haemostatic balance, tissue remodeling, tumor invasion, angiogenesis and reproduction. The main enzyme of the plasminogen activator system is plasmin, which is responsible for the degradation of fibrin into soluble degradation products. The activation of plasminogen into plasmin is mediated by two types of activators, urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA). The activity of both is regulated by specific plasminogen activator inhibitors (PAIs). There are 3 types of PAIs described so far but the most important fibrinolytic inhibitor in vivo is PAI type 1 (PAI-1). Among others, the presence of metabolic syndrome and the -675 4G/5G promoter polymorphism are known to be modulators of PAI-1 levels. Besides their fibrinolytic profile, plasmin and plasminogen activators are implicated in tissue proliferation and cellular adhesion, as they can proteolytically degrade the extracellular matrix and regulate the activation of both growth factors and matrix metalloproteinases. By all these means, the fibrinolytic system is also involved in physiological processes, and in pathological situations such as thrombosis, arteriosclerosis, endometriosis and cancer. PAI 1 has been studied in different settings with thrombotic pathophysiology, such as coronary artery disease and ischaemic stroke. Controversial results have been published and concerns about study designs or presence of confounders have been claimed to be responsible of them. Recently, its involvement in adverse thrombotic events related to the modern drug-eluting coronary stents has renewed the interest of its study. PAI-1 also plays an important role in signal transduction, cell adherence, and migration. Indeed, studies of several types of cancers, including breast cancer, have shown that increased uPA and PAI-1 levels are associated with aggressive tumor behavior and poor prognosis. Endometriosis is defined by the presence of endometrial glands and stroma outside the uterus with marked ability to attach and invade the peritoneum. It is one of the most frequent benign gynecological diseases that affect women with pelvic pain or infertility during their reproductive age. Immune system disorders, genetic predisposition, altered peritoneal environment and endometrial alterations are believed to increase the susceptibility to endometriosis. The plasminogen activator system may be involved in this process, where local extracellular proteolysis plays a crucial role. Altered expression of several components of the fibrinolytic system in both eutopic and ectopic endometrium and peritoneal fluid of women with the disease has been implicated not only in the onset, but also in the progression of the endometriotic lesions.

Protein C inhibitor (PCI) is a heparin-dependent serine protease inhibitor found in human plasma, urine, and other body fluids. In blood plasma, PCI is present at approximately 0.08 microM and inactivates activated protein C and other coagulation and fibrinolytic enzymes. In seminal plasma, PCI is present at 2.2 to 3.7 microM. The main sources of seminal PCI are the seminal vesicles, where it remains fully active. Following ejaculation, PCI completely looses its activity in approximately 2 hours, when it partially complexes with prostate-specific antigen, two plasminogen activators (urokinase-type and tissue-type plasminogen activators), and tissue kallikrein. PCI is also present in an active form in follicular fluid at approximately 0.1 microM. Purified functionally active human blood plasma-derived as well as inactive semen-derived PCI inhibited both binding and penetration of zona-free hamster oocytes by human sperm. The binding inhibition by PCI was dose dependent. A concentration of 0.04 microM PCI (approximately 100-fold lower than that present in seminal plasma) inhibited 50% of the binding and penetration ability. Given that capacitated sperm used for in vitro fertilization usually contains more than 0.05 microM of PCI, fertilization rates might be significantly reduced. All of these data suggest that PCI is involved in human reproduction at several steps, including the fertilization process.

Objective: To perform an analysis comparing long-term survival in heart transplant (HT) patients depending on the immunosuppressive regimen., Materials and Methods: The study included 317 consecutive HT patients. We excluded pediatric cases, retransplants, combined transplants (lung and kidney), and immunosuppressive regimens with fewer than 10 cases. The six groups analyzed were: (1) OKT3 7 days + cyclosporine (CsA) + mycophenolate mofetil (MMF) + steroids (S); (2) OKT3 7 days + CsA + azathioprine (AZA) + S; (3) OKT3 10 days + CsA + MMF + S; (4) OKT3 10 days + CsA + AZA + S; (5) interleukin-2 (IL-2) antagonists + CsA + MMF + S; and (6) IL-2 antagonists + tacrolimus + MMF + S. Probability of survival was analyzed by Kaplan-Meier and log-rank methods., Results: The groups were heterogeneous regarding the number of patients and follow-up. The baseline characteristics were similar, although there were differences in surgery times. The survivals by groups at the end of the follow-up period were: group 1: 75.8%; group 2: 51.2%; group 3: 63.6%; group 4: 25.3%; group 5: 91.2%; and group 6: 84.6%. A major reduction in survival was observed in the groups that were given induction with OKT3 monoclonal antibodies (groups 1, 2, 3, and 4), particularly when AZA was combined in the maintenance phase (groups 2 and 4) and when the induction dose was high (10-day therapy in groups 3 and 4)., Conclusions: Our study suggested an association between the immunosuppressive regimen and the long-term survival of HT patients. The best results were obtained with an induction regimen based on IL-2 antagonists. On the basis of the survivals observed in this study, the maintenance combination we regard as "optimal" at this time is based on a combination of CsA, MMF, and steroids.

Introduction and Objectives: At present, there is some controversy about the impact of diabetes mellitus on heart transplant patients. The effect of the disease on mortality and on other complications, such as infection or rejection, is unclear. The objective of this study was to investigate these factors in our heart transplant patients., Methods: We studied 365 consecutive patients who underwent heart transplantation between November 1987 and May 2003. We divided them in three groups according to whether they had pretransplantation diabetes (group 1), de novo diabetes (group 2), or no diabetes (group 3). Baseline variables and the development of complications were recorded, and findings were analyzed using Student's t test, chi squared test, and Kaplan-Meier survival analysis., Results: There was no difference in the 1-year or 5-year survival rate between the groups (P=.24 and P=.32, respectively). Patients with pretransplantation and de novo diabetes were older (54.6 years vs 54.9 years vs 50.6 years, P=.04), had a higher prevalence of hypertension (48% vs 36% vs 23%, P=.001), and had more frequently been treated with tacrolimus (10% vs 12% vs 4%, P=.04) or steroids (92% vs 86% vs 70%, P=.001). The incidence of rejection during follow-up was greater in these two groups (64% vs 70% vs 45%, P=.001)., Conclusions: Neither pretransplantation diabetes nor de novo diabetes had a negative impact on survival in our heart transplant patients. The disease's presence was associated with treatment with steroids and tacrolimus. In these patients it would be preferable to individualize immunosuppressive therapy.

Unlabelled: Patients with a heart transplant (HT) may require changes in their immunosuppressive maintenance medication. The basic treatment regimen in our patients consisted of an anticalcineurin agent, an antimetabolite, and a steroid., Objective: We undertook a descriptive study to quantify the incidence and causes of these changes and determine how they occur., Materials and Methods: We included the 432 HT performed at our center from November 1987 to October 2005. The baseline treatment was considered to be the treatment given following HT, and the maintenance treatment was that taken at the time of data collection. Kaplan-Meier survival curves were constructed for the analysis., Results: The most significant change was the switch from azathioprine to mycophenolate mofetil. The survival rate after 17 years was 66%., Conclusions: As in the international registries, there has been an evident reduction in the use of cyclosporine and more particularly of azathioprine, in favor of tacrolimus and mycophenolate mofetil, respectively. No changes in the use of steroids have been observed. These data reflect an increasingly greater use of immunosuppressive agents with reduced side effect profiles.

Background: Brain naturietic peptide (BNP) elevations have been reported in heart transplant patients both at baseline and during rejection. An association between BNP levels and certain echocardiographic and hemodynamic abnormalities has also been found in nontransplanted heart disease patients. We sought to determine whether BNP values were correlated with echocardiographic and hemodynamic parameters among a large cohort of heart transplant patients., Materials and Methods: We studied 71 consecutive heart transplant patients, excluding combined grafts, retransplants, and pediatric cases. We performed 488 BNP determinations during catheterization and within 48 hours of echocardiography. Hemodynamic parameters included mean pulmonary artery pressure, right ventricular systolic and diastolic pressures. Doppler echocardiography parameters were wall thickness, ventricular mass, left and right ventricular end-diastolic and end-systolic diameters, isovolumic relaxation time, and mitral flow deceleration time., Results: We observed significant correlations between BNP values and left ventricular size, ventricular mass, and a restrictive filling pattern. BNP levels were also significantly correlated with right ventricular size, mean pulmonary artery pressure, and right ventricular diastolic and end-diastolic pressures., Conclusions: In heart transplant patients, BNP levels positively correlated with ventricular diameters and a restrictive filling pattern. An increase in right ventricle and pulmonary artery pressures was associated with elevated BNP values.

The use of amiodarone before transplantation has been linked to an increased number of complications, acute graft failures, and early mortality after a heart graft. We undertook a retrospective, descriptive, case-controlled study involving early mortality and acute graft failure. The 396 consecutive patients included 25 subjects who had been prescribed amiodarone for at least 30 days before transplantation. We excluded retransplantations, pediatric transplantations, and combined transplantations. The endpoints were early mortality and acute graft failure. No significant differences were observed in early mortality and acute graft failures. The multivariate analysis did not reveal any variable that correlated with early mortality. Our study did not support the idea that amiodarone constituted a negative predictor of early survival or acute graft failure.

Unlabelled: Since their introduction onto the market, interleukin-2 antagonists have been increasingly used by a growing number of transplant units. Their benefits versus OKT3 appear evident, although the optimal dose remains to be established. Our objective was to establish possible differences related to the use of two versus five doses of daclizumab., Materials and Methods: This study evaluated 81 consecutive patients treated with two bolus doses of daclizumab (1 mg/kg) on days 1 and 14 posttransplantation. We excluded retransplantations, pediatric transplantations, and combined transplantations. We compared our series to a previous trial involving the administration of a single bolus dose every 14 days (five boluses in total). Study variables included the number of graft rejections, the number of infections, and the mortality. Statistical analysis was performed using the chi square and Student's t tests. Significance was set at P < .05., Results: There were no differences between groups in the baseline characteristics of the patients. The number of rejection episodes during the first year was significantly lower among the patients in our series treated with two bolus doses of daclizumab than in the series of patients treated with five bolus doses: 24 (30%) vs 17 (61%) episodes (P = .003). No significant differences were observed for mortality: the group receiving two boluses registered 10 deaths (12%) versus two (7%) in the group receiving five boluses (P = .4), or infection rate: 11 patients (40%) in the group receiving five bolus versus 31 patients (38%) in the group given two bolus doses (P = .9)., Conclusions: Our results suggested that induction therapy with two doses of daclizumab was at least as effective in preventing rejection as five doses, with no negative effects on patient survival.

Objective: To evaluate the frequency of infection according to the immunosuppressive regimens used in our center., Materials and Methods: From 259 consecutive heart transplants we excluded pediatric cases, retransplants, combined transplants (lung and kidney) and immunosuppressive regimens with fewer than 10 cases. The six groups analyzed were: (1) OKT3 (7 days) + cyclosporine (CsA) + mycophenolate mofetil (MMF) + steroids (S); (2) OKT3 (7 days) + CsA + azathioprine (AZA) + S; (3) OKT3 (10 days) + CsA + MMF + S; (4) OKT3 (10 days) + CsA + AZA + S; (5) interleukin-2 (IL-2) antagonists + CsA + MMF + S; (6) IL-2 antagonists + tacrolimus + MMF + S. Infection was considered significant when it causal hospital admission or prolonged hospitalization., Results: With a total mean follow-up of 54 +/- 43 months, the total percentage of infection-free patients at the end of follow-up was 45.5%. Infection-free survival was lower among patients administered induction with OKT3 antibodies for 10 days, combined with cyclosporine, either with MMF (10%, group 3) or with azathioprine (27%, group 4), compared to those given IL-2 antagonists (particularly in combination with tacrolimus and MMF-69.2%, group 6)., Conclusions: The results of this study showed that infection was frequent in heart transplantation. Furthermore, induction therapy with OKT3 monoclonal antibodies was associated with an important number of infections (particularly viral infections). Comparison of the treatment groups showed that the regimen associated with fever infections included an IL-2 receptor antagonist with tacrolimus, MMF, and S.

Background: Cardiovascular risk factors for myocardial infarction (MI) are less frequent in younger than in older MI survivors. Therefore, the thrombotic component of MI may play a more important role at a young age. As activated protein C (APC) provides systemic anticoagulant and anti-inflammatory protection, a low plasma APC level may be an arterial thrombotic risk factor., Aim: To determine whether there is an association between reduced APC levels and early MI and severe coronary lesions., Methods: APC was measured in 231 young MI survivors and 231 controls., Results: Low APC levels were significantly associated with MI. Compared with the fourth quartile, the odds ratio (OR) for APC values in the first quartile was 3.7 [95% confidence interval (CI) = 2.1-6.4], and 3.2 (1.5-7.0) after adjustment for cardiovascular risk factors. Moreover, each decrease of 0.43 ng mL(-1) (1 SD) in APC increased the OR 1.7 times (1.4-2.2), and 1.5 times (1.2-1.9) after adjustment for cardiovascular risk factors. Low APC levels were also associated with the number of coronary arteries affected and with the severity of coronary lesions (P < 0.001)., Conclusions: There is a significant association between low circulating APC levels and both early MI and the extent and severity of coronary atherosclerosis, which might be related to the anticoagulant and anti-inflammatory properties of APC.

The purpose of this study was to evaluate whether high levels and small isoforms of lipoprotein (a) [Lp(a)] are markers of risk of early myocardial infarction and markers of the severity of coronary atherosclerosis. Lp(a) levels and small apo(a) isoforms were higher in 222 patients than in 199 controls (p<0.001). In patients, Lp(a)> or =30 mg/dL was associated with the presence of coronary lesions (p=0.007) and the severity of coronary atherosclerosis (p=0.002). The present study suggests that Lp(a) levels and small isoforms are markers of early myocardial infarction and that Lp(a) levels > or =30 mg/dL are associated with severe patterns of coronary atherosclerosis.

Background and Aims: Immunosuppressive therapy has undergone great changes in recent years as a result of the introduction of new drugs, presumed a prior to be more effective and better tolerated. The greatest advance seems to have been the introduction of interleukin-2 (IL-2) receptor antagonists. The objective of this study was to determine whether the use of IL-2 receptor antagonists in induction therapy has implications for the development of rejection and survival., Materials and Methods: Three hundred sixty-five consecutive cardiac transplant patients who received induction therapy were included. Heart-lung and transplants in children under 10 years were excluded. Three groups were compared according to the induction therapy (OKT3, 10 days; OKT3, 7 days; and IL-2R antagonists). Each treatment corresponded to a time period: OKT3 10 days from June 1989 to April 1994; OKT3 7 days from May 1994 to October 2002; and IL-2R antagonists from November 2002 to May 2004. Baseline characteristics of recipient and donor, surgical times, postsurgical complications, maintenance immunosuppression, number of rejections, time (days) to first rejection, and probability of survival at 1 year were recorded. We used analysis of variance, chi(2) test, Kaplan-Meier curves, and log-rank test as appropriate. A P-value < .05 was considered significant., Results: There were significant differences in the characteristics of the transplanted patients in the various time periods. Thus, recipients in the OKT3 10 day group had worse status but better donors, whereas recipients in the IL-2R antagonists group had better status but older donors with longer duration of ischemia. The incidence of acute graft failure was similar in the three groups. The number of rejection episodes in the first year was higher among the OKT3 groups (OKT3 10 days, 1.7 +/- 1.3; OKT3 7 days, 1.2 +/- 1.2; IL-2R antagonists, 1.0 +/- 1.2; P = .02) and the probability of survival at 1 year was also lower (OKT3 10 days, 74%; OKT3 7 days, 77%; IL-2R antagonists, 94%; P = .0007)., Conclusions: Induction therapy with IL-2 antagonists offers important advantages over treatment with OKT3 in terms of survival, with absolute and relative risk reductions of 20% and 27%. Furthermore, it did not increase the number of rejections, although this may have been due to the greater use of MMF versus azathioprine.

Background: Certain cardiovascular risk factors have been linked to morbidity and mortality in heart transplant (HT) patients. The sum of various risk factors may have a large cumulative negative effect, leading to a substantially worse prognosis and the need to consider whether HT is contraindicated. The objective of this study was to determine whether the risk factors usually available prior to HT result in an excess mortality in our setting that contraindicates transplantation., Materials and Methods: Consecutive patients who underwent heart transplantation from November 1987 to January 2004 were included. Heart-lung transplants, retransplants, and pediatric transplants were excluded. Of the 384 patients, 89% were men. Mean age was 52 years (range, 12 to 67). Underlying disease included ischemic heart disease (52%), idiopathic dilated cardiomyopathy (36%), valvular disease (8%), and other (4%). Variables considered risk factors were obesity (BMI >25), dyslipidemia, hypertension, prior thoracic surgery, diabetes, and history of ischemic heart disease. Survival curves by number of risk factors using Kaplan-Meier and log-rank for comparison of curves., Results: Overall patient survival at 1, 5, 10, and 13 years was 76%, 68%, 54%, and 47%, respectively. Survival at 10 years, if fewer than two risk factors were present, was 69%; 59% if two or three factors were present; and 37% if more than three associated risk factors were present (P = .04)., Conclusions: The presence of certain risk factors in patients undergoing HT resulted in lower survival rates. The combination of various risk factors clearly worsened outcomes. However, we do not believe this should be an absolute contraindication for transplantation.

The protein C pathway is a major regulator of blood coagulation, since it controls the conversion of prothrombin to thrombin through a feedback inhibition mechanism. Protein C circulates in plasma as an inactive zymogen and is activated on the surface of endothelial cells by the thrombin-thrombomodulin complex, a process that can be further enhanced when protein C binds to its membrane receptor, the endothelial-cell protein C receptor. Activated protein C (APC) is then released from the complex, binds protein S and inhibits thrombin formation by inactivating coagulation factors Va and VIIIa. The importance of the protein C anticoagulant pathway is emphasized by the increased risk of venous thromboembolism (VTE) associated with protein C and protein S deficiencies, the factor V Leiden mutation, and reduced circulating APC levels. The protein C pathway also plays a significant role in inflammatory processes, since it prevents the lethal effects of E. coli-associated sepsis in animal models and improves the outcome of patients with severe sepsis. APC seems to display anti-apoptotic and neuroprotective activities. Thus, it reduces organ damage in animal models of sepsis, ischemic injury, endothelial cell injury, or stroke. Further research will hopefully widen the current therapeutic perspectives in all these illnesses, where these effects might play a crucial role in their treatment. This review will summarize the mechanisms that contribute to these biological activities of the protein C pathway.

Epsilon wave is an unusual electrocardiographical finding, which may appear in other pathological conditions besides the arrhythmogenic right ventricular dysplasia, particularly in the acute myocardial infarction of the right ventricle, the inferior, or the posterior wall of the left ventricle. Its real incidence in these acute coronary syndromes remains unknown and will be probably difficult to assert, since it may be unnoticed by inexperienced physicians because of its little voltage. The outstanding interest of this case lies in the clear electrocardiographical images and in the step-by-step differential diagnosis discussed by the authors.

Aim: To evaluate the pattern of brain natriuretic peptide (BNP) concentration in heart transplant (HT) recipients and its relation to the degree of graft rejection determined by endomyocardial biopsy specimen., Methods: We studied 71 consecutive HT recipients (62 men, 53 +/- 11 years). The patients underwent 383 biopsies. Creatinine and BNP concentrations and hemodynamic parameters were determined along with the degree of graft rejection using endomyocardial biopsy specimens. We considered treatable rejection as International Society for Heart and Lung Transplantation Grade >or=2 in the first 90 days and >or=3A thereafter. We included a control group of 36 healthy individuals., Results: Brain natriuretic peptide concentration was significantly greater among HT recipients (264 +/- 318 pg/ml) than in controls (17 +/- 16 pg/ml). In the first 90 days, BNP concentration was significantly greater among the patients with graft rejection (510 +/- 470, n = 84, vs 278 +/- 255, n = 87; p < 0.0001), although the corresponding discriminatory capacity was small. After the first 90 days, BNP values were similar in patients with and without graft rejection (170 +/- 297, n = 17, vs 142 +/- 203, n = 195; p = not significant). Creatinine concentration increased with time after transplantation and did not correlate with BNP concentration. We observed significant positive correlation between BNP concentration and hemodynamic parameters., Conclusions: Brain natriuretic peptide concentration remains increased after HT, with stabilization after the 4th month. Brain natriuretic peptide concentrations are slightly greater among patients with treatable rejection, particularly in the first 90 days, although BNP concentration lacks discriminatory capacity to serve as a guide to performing biopsy.

Thrombin-activatable fibrinolysis inhibitor (TAFI) is a fibrinolytic inhibitor. Studies in coronary artery disease have reported increased TAFI activity (TAFI Act) and low TAFI antigen (TAFI Ag) levels. This controversy might be explained by the polymorphisms of its gene. Only the Thr325Ile polymorphism modulates both TAFI Ag and Act levels in vitro. This study assessed TAFI Ag and Act levels, TAFI Thr325Ile polymorphism, the fibrinolytic and protein C systems and some prothrombotic mutations in a young patient group (n = 127, aged < 51 years, with myocardial infarction) and a control group (n = 99) with similar characteristics. Patients exhibited hypofibrinolysis and higher plasminogen activator inhibitor-1 (PAI-1) levels. Although TAFI Ag was lower, TAFI Act level was significantly higher in patients and positively correlated with PAI-1, protein C inhibitor and the euglobulin lysis time. No differences between groups were found according to the Thr325Ile polymorphism. Irrespective of the genotype, patients had higher TAFI Act levels. The Ile-325 variant exhibited lower TAFI Ag levels. We suggest that the hypofibrinolysis observed in these patients results from an increase in both PAI-1 and TAFI Act, which is not related to the Thr325Ile polymorphism. Patients have high TAFI Act with low TAFI Ag levels, probably because of an increased stability of TAFI related to a fibrinolytic hypofunction.

Background: Endometriosis is considered a benign disease that has the ability to invade normal tissue. As in neoplastic growth, local extracellular proteolysis may take place. The aim of this study is to analyse several components of the plasminogen activator (PA) pathway and the matrix metalloproteinase (MMP) system in endometriotic tissue, endometrium and peritoneal fluid from women with and without endometriosis (controls)., Methods and Results: Thirty-nine women with endometriosis and 35 controls were studied. In eutopic endometrium of women with endometriosis, the antigenic levels of urokinase-type PA (uPA) and MMP-3 were elevated when compared with endometrium from controls. Ovarian endometriotic tissues had higher antigenic levels of PA inhibitor type 1 (PAI-1) and tissue inhibitor of metalloproteinases type 1 (TIMP-1) than endometrium. The peritoneal fluid from women with endometriosis showed a significant increase in uPA levels compared with controls., Conclusions: The increase in antigenic levels of uPA and MMP-3 in endometrium of women with endometriosis might contribute to the invasive potential of endometrial cells. Once the ovarian endometriotic cyst is developed, an increase in PAI-1 and TIMP-1 is detected and significant proteolytic activity is no longer observed. This increase in inhibitors and decrease in proteolytic activity could explain the frequent clinical finding of isolated endometriotic cyst without invasion of the surrounding ovarian tissue.

Introduction and Objectives: In acute anterior myocardial infarction (AMI), the site of occlusion in the left anterior descending coronary artery (LAD) is related to the extension of myocardial necrosis and the prognosis. The aim of this study was to assess the value of the electrocardiogram (ECG) as a predictor of the LAD occlusion site in patients with anterior AMI., Methods: Forty-five consecutive patients with a first anterior AMI and isolated disease of the LAD were included. We evaluated retrospectively the ECG with the most pronounced ST-segment changes before fibrinolysis and correlated the findings with the site of LAD occlusion in angiography before hospital discharge in relation to the first dominant septal and first diagonal branch: first septal affected (S), first diagonal affected (D), both affected (S + D), or neither affected were considered., Results: ST depression in leads II, III, or aVF strongly predicted proximal LAD occlusion in S + D, S, and D (p = 0,003, p = 0,04, and p = 0,02, respectively). ST elevation in leads II, III, or aVF was observed only in the presence of wrap-around LAD and was related with occlusion distal to the first diagonal branch. ST elevation > or = 3 mm in lead V1 was a specific predictor of occlusion proximal to first septal (S, p = 0,01). ST elevation in aVR was associated with proximal LAD occlusion in S + D and S (p = 0,03 and p = 0,03, respectively) and absence of coronary collateral circulation., Conclusions: In anterior AMI and isolated LAD disease, the ECG can be useful in predicting the LAD occlusion site in relation to its major side branches.