Left atrial strain in adults after the arterial switch operation for transposition of the great arteries.

BACKGROUND: No study has focused on left atrial (LA) function assessed by echocardiography in adult patients with simple D-TGA after arterial switch operation (ASO). We aimed to describe LA strain parameters in these patients. METHODS: A prospective cohort study including 42 adult patients with simple D-TGA after ASO and 33 aged-matched controls. Phasic LA and LV global longitudinal strain (GLS) were obtained by transthoracic 2D-speckle tracking echocardiography (STE). Volumetric and functional analysis of LA and LV were also evaluated by 2D and 3D analysis. A multivariable model was performed to investigate the variables that best differentiate patients with D-TGA from healthy controls. RESULTS: LA strain parameters in D-TGA patients were within the normal range described for healthy subjects. However, the three LA strain parameters (Reservoir, Conduit, and Contraction) were lower in patients (LASr: 31.13 ± 7.67 vs. 49.71 ± 8.38; LAS cd: -22.91 ± 5.69 vs. -34.55 ± 6.54; LASct: -8.14 ± 4.93 vs. -15.15 ± 6.07, p < .001 for all three comparisons). LA volumes were similar between patients and controls. LV-GLS remained significantly lower in the D-TGA group than in controls (-17.29 ± 2.68 vs. -21.98 ± 1.84, p < .001). D-TGA patients had evidence of worse LV ejection fraction measured by the Teichholz method (63.38 ± 8.23 vs. 69.28 ± 5.92, p = .001) and 3D analysis (57.97% ± 4.16 vs. 60.67 ± 3.39, p = .011) and diastolic dysfunction as compared to healthy controls. LV-GLS and conduit LAS were the variables best differentiating patients with D-TGA from healthy controls. CONCLUSIONS: LA strain is impaired in young adults with simple D-TGA late after the ASO, probably in agreement with some degree of LV dysfunction previously described.

Safety and feasibility of conduction system pacing in patients with congenital heart disease.

INTRODUCTION: Conduction system pacing (CSP) has emerged as an ideal physiologic pacing strategy for patients with permanent pacing indications. We sought to evaluate the safety and feasibility of CSP in a consecutive series of unselected patients with congenital heart disease (CHD). METHODS: Consecutive patients with CHD in which CSP was attempted were included. Safety and feasibility, implant tools and electrical parameters at implant and at follow-up were evaluated. RESULTS: A total of 20 patients were included (10 with a previous device). A total of 10 patients had complex forms of CHD, 9 moderate defects and 1 a simple defect. CSP was achieved in 75% of cases (10 His bundle pacing, 5 left bundle branch pacing) with left ventricular septal pacing in the remaining 5 patients. Procedure times and fluoroscopy times were prolongued (126 ± 82 min and 27 ± 30 min, respectively). Ventricular lead implant times widely varied ranging from 4 to 115 min, (mean 31 ± 28 min) and the use of multiple delivery sheaths was frequent (50%). The QRS width was reduced from 145 ± 36 ms at baseline to 116 ± 18 ms with CSP. Implant electrical parameters included: CSP pacing threshold 0.95 ± 0.65 V; R wave amplitude 9.2 ± 8.8 mV and pacing impedance 632 ± 183 Ohms, and remained stable at a median follow-up of 478 days (interquartile range: 225-567). Systemic ventricle systolic function and NYHA class (1.50 ± 0.51 vs. 1.10 ± 0.31; p = .008) significantly improved at follow-up. Lead revision was required in one patient at Day 4. CONCLUSIONS: Permanent CSP is safe and feasible in patients with CHD although implant technique is complex.

The use of fluorescence in situ hybridization analysis on sperm: indications to perform and assisted reproduction technology outcomes.

PURPOSE: To determine the consequences of an altered sperm fluorescence in situ hybridization (FISH) result for ART outcomes and the indications for a sperm FISH analysis. METHODS: Data from 439 infertile men were collected. Bivariate analyses were performed to determine the association of men's age, seminal alterations, and sperm FISH indication, with the incidence of X, Y, 13, 18, and 21 sperm chromosomal abnormalities. A multivariate logistic regression analysis was performed to establish the most predictive variables for altered sperm FISH. Results from the IVF/ICSI cycles were collected for 248 out of 439 patients. Two distinct groups were established: 151 couples that used their own oocytes and 97 couples involved in egg donation programs. In both groups, ART outcomes were compared between normal and altered sperm FISH. RESULTS: Teratozoospermia and oligozoospermia were associated with sperm chromosome anomalies (p < 0.05). Indications for sperm FISH analysis with the highest predictability were teratozoospermia, male age, oligozoospermia, and implantation failure (AUC = 0.702). Embryo quality (p = 0.096), pregnancy rate (p = 0.054), and implantation rate (p = 0.089) were higher in own-oocytes couples with normal sperm FISH than in altered sperm FISH couples, although differences were not statistically significant. In donor-oocytes couples, in which high-quality embryos were transferred later than in own-oocytes couples (3.8 vs. 3.0 days), we did not identify differences in the ART outcome between normal and altered sperm FISH couples. In both groups, the possible interference of woman age was negligible. CONCLUSIONS: Sperm FISH is indicated in middle-aged oligoteratozoospermic patients with implantation failures in previous IVF/ICSI cycles. Sperm chromosome anomalies have a moderate detrimental impact on embryo quality, implantation, and pregnancy rates.

The Role of Conventional and Right-Sided ECG Screening for Subcutaneous ICD in a Tetralogy of Fallot Population.

BACKGROUND: Information regarding suitability for subcutaneous implantable cardioverter-defibrillator (S-ICD) implant in tetralogy of Fallot (ToF) population is scarce and needs to be further explored. THE AIMS OF OUR STUDY WERE: (1) to determine the proportion of patients with ToF eligible for S-ICD, (2) to identify the optimal sensing vector in ToF patients, (3) to test specifically the eligibility for S-ICD with right-sided screening, and (4) to compare with the proportion of eligible patients in a nonselected ICD population. METHODS: We recruited 60 consecutive patients with ToF and 40 consecutive nonselected patients. Conventional electrocardiographic screening was performed as usual. Right-sided alternative screening was studied by positioning the left arm and right arm electrodes 1 cm right lateral to the xiphoid midline. The Boston Scientific electrocardiogram (ECG) screening tool was utilized. RESULTS: We found a higher proportion of patients with right-sided positive screening in comparison with standard screening (77 ± 0.4% vs. 67 ± 0.4%; P < 0.0001) and a trend to higher number of appropriate leads in right-sided screening (1.3 ± 1 vs. 1.1 ± 1 ms; P = 0.07). Patients who failed the screening had a longer QRS duration and longer QT interval. Standard and right-sided screening showed a higher percent of positive patients in the control group compared to ToF patients (P < 0.001). CONCLUSION: Right-sided screening was associated with a significant 10% increase in S-ICD eligibility in ToF patients. When comparing with an acquired cardiomyopathies group, ToF showed a lower eligibility for S-ICD. The most appropriate ECG vector was the alternate vector in contrast to what is observed in the general population.

Conventional and right-sided screening for subcutaneous ICD in a population with congenital heart disease at high risk of sudden cardiac death.

BACKGROUND: Information regarding suitability for subcutaneous defibrillator (sICD) implantation in tetralogy of Fallot (ToF) and systemic right ventricle is scarce and needs to be further explored. The main objective of our study was to determine the proportion of patients with ToF and systemic right ventricle eligible for sICD with both, standard and right-sided screening methods. Secondary objectives were: (i) to study sICD eligibility specifically in patients at high risk of sudden cardiac death, (ii) to identify independent predictors for sICD eligibility, and (iii) to compare the proportion of eligible patients in a nonselected ICD population. METHODS: We recruited 102 patients with ToF, 33 with systemic right ventricle, and 40 consecutive nonselected patients. Conventional electrocardiographic screening was performed as usual. Right-sided alternative screening was studied by positioning the left-arm and right-arm electrodes 1 cm right lateral of the xiphoid midline. The Boston Scientific ECG screening tool was utilized. RESULTS: In high-risk patients with ToF, eligibility was higher with right-sided screening in comparison with standard screening (61% vs. 44%; p = .018). Eligibility in high-risk right ventricle population was identical with both screening methods (77%, p = ns). The only independent predictor for sICD eligibility was QRS duration. CONCLUSION: In high-risk patients with ToF, right-sided implantation of the sICD could be an alternative to a conventional ICD. In patients with a systemic right ventricle, implantation of a sICD is an alternative to a conventional sICD.

Essential ECG clues in patients with congenital heart disease and arrhythmias.

The prevalence of adults with congenital heart disease has dramatically increased during the last decades due to significant advances in the surgical correction of these conditions. As a result, patient's survival has been prolonged and arrhythmias have become one of the principal causes of morbidity and mortality for these patients. The surface 12-lead ECG may play a critical role in the identification of the underlying heart disease of the patient, the recognition of the arrhythmia mechanism and may also help in the planification of the ablation procedure in this setting. Finally, important prognostic information can be also obtained from the ECG in these patients. The present review will offer an overview of the principal utilities of the surface ECG in the diagnosis and management of patients with CHD and arrhythmias.

ß2- and ß1-Adrenoceptor Expression Exhibits a Common Regulatory Pattern With GRK2 and GRK5 in Human and Animal Models of Cardiovascular Diseases.

To explore if genic expression of ß(1)- or ß(2)-adrenoceptors (ARs) exhibits a common regulatory pattern with G protein-coupled receptor kinase (GRK) 2, GRK3, or GRK5 expression, we determined messenger RNA levels for these genes in different tissues from human and animal models of cardiovascular disease. We measured genic expression by qRT polymerase chain reaction in the left and right ventricles or peripheral blood mononuclear cells from healthy (n = 21), hypertensive (n = 20), heart failure (n = 24), and heart transplanted patients (n = 17) or in left ventricle, peripheral blood mononuclear cells, and kidney from spontaneously hypertensive rats or L-N-methyl-arginine-induced hypertensive rats and their respective controls (n = 4-5). In diseased versus healthy subjects and rats, parallel changes in messenger RNA levels of GRK2 and ß(2)-AR or GRK5 and ß(1)-AR were observed in each territory. Therefore, without excluding other regulatory mechanisms, the parallelism observed suggests a common regulatory pattern for the ß(1)-AR/GRK5 and ß(2)-AR/GRK2 genes, which is independent of cellular type or pathology. This highlights the need to focus not only on GRKs but also on ß(1)- or ß(2)-AR changes to completely understand the involvement of ß-AR/GRK pathways in cardiovascular diseases.

Decreased clinical performance in TGA-ASO patients after RVOT interventions; a multicenter European collaboration.

BACKGROUND: In patients with transposition of the great arteries and an arterial switch operation (TGA-ASO) right ventricular outflow tract (RVOT) obstruction is a common complication requiring one or more RVOT interventions. OBJECTIVES: We aimed to assess cardiopulmonary exercise capacity and right ventricular function in patients stratified for type of RVOT intervention. METHODS: TGA-ASO patients (≥16 years) were stratified by type of RVOT intervention. The following outcome parameters were included: predicted (%) peak oxygen uptake (peak VO2), tricuspid annular plane systolic excursion (TAPSE), tricuspid Lateral Annular Systolic Velocity (TV S'), right ventricle (RV)-arterial coupling (defined as TAPSE/RV systolic pressure ratio), and N-terminal proBNP (NT-proBNP). RESULTS: 447 TGA patients with a mean age of 25.0 (interquartile range (IQR) 21-29) years were included. Patients without previous RVOT intervention (n = 338, 76%) had a significantly higher predicted peak VO2 (78.0 ± 17.4%) compared to patients with single approach catheter-based RVOT intervention (73.7 ± 12.7%), single approach surgical RVOT intervention (73.8 ± 28.1%), and patients with multiple approach RVOT intervention (66.2 ± 14.0%, p = 0.021). RV-arterial coupling was found to be significantly lower in patients with prior catheter-based and/or surgical RVOT intervention compared to patients without any RVOT intervention (p = 0.029). CONCLUSIONS: TGA patients after a successful arterial switch repair have a decreased exercise capacity. A considerable amount of TGA patients with either catheter or surgical RVOT intervention perform significantly worse compared to patients without RVOT interventions.

Different expression of adrenoceptors and GRKs in the human myocardium depends on heart failure etiology and correlates to clinical variables.

Downregulation of ß(1)- adrenergic receptors (ß(1)-ARs) and increased expression/function of G-protein-coupled receptor kinase 2 (GRK2) have been observed in human heart failure, but changes in expression of other ARs and GRKs have not been established. Another unresolved question is the incidence of these compensatory mechanisms depending on heart failure etiology and treatment. To analyze these questions, we quantified the mRNA/protein expressions of six ARs (α(1A), α(1B), α(1D), ß(1), ß(2), and ß(3)) and three GRKs (GRK2, GRK3, and GRK5) in left (LV) and right ventricle (RV) from four donors, 10 patients with ischemic cardiomyopathy (IC), 14 patients with dilated cardiomyopathy (DC), and 10 patients with nonischemic, nondilated cardiopathies (NINDC). We correlated the changes in the expressions of ARs and GRKs with clinical variables such as left ventricular ejection fraction (LVEF) and left ventricular end-systolic and left ventricular end-diastolic diameter (LVESD and LVEDD, respectively). The main findings were 1) the expression of the α(1A)-AR in the LV positively correlates with LVEF; 2) the expression of GRK3 and GRK5 inversely correlates with LVESD and LVEDD, supporting previous observations about a protective role for both kinases in failing hearts; and 3) ß(1)-AR expression is downregulated in the LV and RV of IC, in the LV of DC, and in the RV of NINDC. This difference, better than an increased expression of GRK2 (not observed in IC), determines the lower LVEF in IC and DC vs. NINDC.

Myocardial G protein receptor-coupled kinase expression correlates with functional parameters and clinical severity in advanced heart failure.

BACKGROUND: In heart failure (HF), sympathetic hyperactivation induces deleterious effects in myocardial ß-adrenergic signaling, with receptor down-regulation and desensitization mediated by G protein receptor-coupled kinases (GRKs). We hypothesised that changes in GRK isoforms may be associated with clinical status in advanced HF, using the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) scale. METHODS: We included 31 patients with advanced HF undergoing transplantation. According to INTERMACS profiles, mRNA and protein levels of GRK isoforms in left ventricular (LV) myocardium were analyzed and compared with nonfailing LV samples. RESULTS: In failing LV myocardium, GRK2 and GRK5 (but not GRK3) protein was up-regulated compared with control samples. Among HF patients, an increase in GRK2 and GRK5 mRNA and protein abundance was observed in ß-agonist-treated patients (vs ß-blockers: P < .05) and in higher-risk INTERMACS status (profiles 2 and 3 vs 4 and 5: P < .05). A significant negative correlation of GRK2 expression with LV stroke volume supported these findings. CONCLUSIONS: Increased GRK2 correlates with clinical severity using the INTERMACS scale and LV stroke volume, supporting it as a potential target in advanced HF. These changes are paralleled by GRK5 expression in the failing myocardium, suggesting a relevant role in human HF.

Predicting sudden cardiac death in adults with congenital heart disease.

OBJECTIVES: To develop, calibrate, test and validate a logistic regression model for accurate risk prediction of sudden cardiac death (SCD) and non-fatal sudden cardiac arrest (SCA) in adults with congenital heart disease (ACHD), based on baseline lesion-specific risk stratification and individual's characteristics, to guide primary prevention strategies. METHODS: We combined data from a single-centre cohort of 3311 consecutive ACHD patients (50% male) at 25-year follow-up with 71 events (53 SCD and 18 non-fatal SCA) and a multicentre case-control group with 207 cases (110 SCD and 97 non-fatal SCA) and 2287 consecutive controls (50% males). Cumulative incidences of events up to 20 years for specific lesions were determined in the prospective cohort. Risk model and its 5-year risk predictions were derived by logistic regression modelling, using separate development (18 centres: 144 cases and 1501 controls) and validation (two centres: 63 cases and 786 controls) datasets. RESULTS: According to the combined SCD/SCA cumulative 20 years incidence, a lesion-specific stratification into four clusters-very-low (<1%), low (1%-4%), moderate (4%-12%) and high (>12%)-was built. Multivariable predictors were lesion-specific cluster, young age, male sex, unexplained syncope, ischaemic heart disease, non-life threatening ventricular arrhythmias, QRS duration and ventricular systolic dysfunction or hypertrophy. The model very accurately discriminated (C-index 0.91; 95% CI 0.88 to 0.94) and calibrated (p=0.3 for observed vs expected proportions) in the validation dataset. Compared with current guidelines approach, sensitivity increases 29% with less than 1% change in specificity. CONCLUSIONS: Predicting the risk of SCD/SCA in ACHD can be significantly improved using a baseline lesion-specific stratification and simple clinical variables.

Clinical outcome of COVID-19 in patients with adult congenital heart disease.

AIMS: Patients with adult congenital heart disease (ACHD) are a potentially vulnerable patient cohort in case of COVID-19. Some cardiac defects may be associated with a poor COVID-19 outcome. Risk estimation in ACHD is currently based on expert opinion. The aim of this study was to collect clinical outcome data and to identify risk factors for a complicated course of COVID-19 in patients with ACHD. METHODS: Twenty-five ACHD centres in nine European countries participated in the study. Consecutive patients with ACHD diagnosed with COVID-19 presenting to one of the participating centres between 27 March and 6 June 2020 were included. A complicated disease course was defined as hospitalisation for COVID-19 requiring non-invasive or invasive ventilation and/or inotropic support, or a fatal outcome. RESULTS: Of 105 patients with a mean age of 38±13 years (58% women), 13 had a complicated disease course, of whom 5 died. In univariable analysis, age (OR 1.3, 95% CI 1.1 to 1.7, per 5 years), ≥2 comorbidities (OR 7.1, 95% CI 2.1 to 24.5), body mass index of >25 kg/m2 (OR 7.2, 95% CI 1.9 to 28.3) and cyanotic heart disease (OR 13.2, 95% CI 2.5 to 68.4) were associated with a complicated disease course. In a multivariable logistic regression model, cyanotic heart disease was the most important predictor (OR 60.0, 95% CI 7.6 to 474.0). CONCLUSIONS: Among patients with ACHD, general risk factors (age, obesity and multiple comorbidities) are associated with an increased risk of complicated COVID-19 course. Congenital cardiac defects at particularly high risk were cyanotic lesions, including unrepaired cyanotic defects or Eisenmenger syndrome.

Evaluation of a near-zero fluoroscopic approach for catheter ablation in patients with congenital heart disease.

PURPOSE: Radiation exposure (RE) is a matter of concern for patients with congenital heart disease (CHD) who not infrequently need multiple interventional procedures under fluoroscopy guidance. We sought to evaluate the safety and feasibility of a minimally fluoroscopic approach in patients with CHD undergoing catheter ablation using a new image integration module (IIM). METHODS: Consecutive patients with CHD undergoing catheter ablation using the Carto Univu™ IIM were included. A near-zero fluoroscopy procedure was defined by an effective dose (ED) ≤ 1 mSv. RE parameters (total fluoroscopy time [TFT], total dose area product [tDAP], and ED), ablation outcomes, and complications were evaluated. RESULTS: Fifty-five patients with CHD underwent 63 ablation procedures (supraventricular tachycardia, n = 53; ventricular tachycardia, n = 10). The CHD was simple in 25%, moderate in 42%, and complex in 33%. The use of the IIM resulted in very low levels of RE (median TFT 0.13 min [IQR 0-1.04], median tDAP 54.5 cGy cm2 [IQR 9.5-176.4], median ED 0.136 mSv [IQR 0.02-0.49]). Patients with complex CHD had significantly higher RE when compared with patients with simple and moderate defects. A total of 56/63 ablation procedures (89%) were performed with an ED ≤ 1 mSv. One patient developed sinus node dysfunction requiring pacemaker implantation. CONCLUSIONS: The use of a minimally fluoroscopic approach was safe and feasible resulting in very low RE during catheter ablation of patients with CHD. A near-zero fluoroscopy ablation was possible in up to 89% of the procedures.

ß2-Adrenoceptors and GRK2 as Potential Biomarkers in Patients With Chronic Pulmonary Regurgitation.

Pulmonary regurgitation (PR) is a frequent complication after repair of congenital heart disease. Three different GRK isoforms (GRK2, GRK5, and GRK3) and two ß-adrenoceptors (ß1-AR and ß2-AR) are present in peripheral blood mononuclear cells (PBMC) and their expression changes as a consequence of the hemodynamic and neurohumoral alterations that occur in some cardiovascular diseases. Therefore, they could be useful as biomarkers in PR. A prospective study was conducted to describe the expression (TaqMan Gene Expression Assays) of ß-ARs and GRKs in PBMC isolated (Ficoll® gradient) from patients with severe PR before and after pulmonary valve replacement and establish if this expression correlates to clinical status. 23 patients with severe PR were included and compared with 22 healthy volunteers (controls). PR patients before the PVR had a significantly lower expression of ß2-AR (513.8 ± 261.2 mRNA copies) vs. controls (812.5 ± 497.2 mRNA copies), so as GRK2 expression (503.4 ± 364.9 copies vs. 858.1 ± 380.3 mRNA copies). The expression of ß2-AR and GRK2 significantly decreases in symptomatic and asymptomatic patients, as well as in patients under treatment with beta-blockers and non-treated patients. The expression of ß2-AR and GRK2 in PR patients recovers the normal values after pulmonary valve replacement (754,8 ± 77,1 and 897,8 ± 87,4 copies, respectively). Therefore, changes in the expression of ß2-AR and GRK2 in PBMC of PR patients, could be considered as potential biomarkers to determine clinical decisions.

Endothelial protein C receptor polymorphisms and risk of myocardial infarction.

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.

Influence of immunosuppressive regimens on short-term morbidity and mortality in heart transplantation.

BACKGROUND: The goal of immunosuppressive therapy in heart transplantation is to maximize safety and efficacy while minimizing morbidity and mortality. We now have numerous drug combinations, but few have been compared with each other. AIM: To compare various immunosuppressive regimens assessing morbidity and mortality at one yr. METHODS: A total of 351 patients transplanted between 1989 and 2005 were included and grouped by immunosuppressive regimen into group 1 (n = 52): Muronomab (OKT3) 10 d, cyclosporine (CSA), azathioprine (AZA), steroids; group 2 (n = 193): OKT3 seven d, CSA, AZA, steroids; group 3 (n = 22): OKT3 seven d, CSA, mycophenolate mofetil (MMF), steroids; and group 4 (n = 84): interleukin-2 antagonists (IL-2), CSA, MMF, steroids. RESULTS: The incidence of acute graft failure and treated rejection was similar between groups (17% and 78% respectively). We found a statistically significant difference in the incidence of infections (p < 0.001), renal dysfunction (p = 0.011) and in diabetes mellitus (p = 0.023). There were no differences in survival at 30 d (97%), but differences were found at one yr (p = 0.011). The multivariate analysis showed a strong association between mortality and infection (p = 0.001) and between survival and the group 4 regimen (p < 0.001). CONCLUSION: There are differences in survival at one yr of heart transplant patients depending on the immunosuppressive regimen used. The best combination was induction with IL-2 antagonists, followed by CSA, MMF and steroids.

Haemorheological parameters in young patients with acute myocardial infarction.

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.

Prenatal diagnosis and molecular cytogenetic characterization of a de novo duplication of 15q24.3-q26.1.

Reported cases of distal 15q interstitial duplications are uncommon and do not result in a recognizable pattern of abnormalities. Some studies report prenatal overgrowth, while others describe growth retardation. We present molecular cytogenetic characterization of a 14 Mb interstitial duplication, encompassing 81 Online Mendelian Inheritance in Man (OMIM) genes, in a fetus with single umbilical artery and short limbs. We propose that growth restriction, previously described and present in our patient, may be due to duplication of a gene or genes contained in the 15q24 region.

Activation of α1A -adrenoceptors desensitizes the rat aorta response to phenylephrine through a neuronal NOS pathway, a mechanism lost with ageing.

BACKGROUND AND PURPOSE: A NO-mediated desensitization of vasoconstrictor responses evoked by stimulation of α1 -adrenoceptors has been reported in different vessels. We investigated the involvement of each α1 -adrenoceptor subtype and constitutive NOS isoforms and the influence of ageing and hypertension on this process. EXPERIMENTAL APPROACH: Wistar and spontaneously hypertensive rats (SHR), 16, 32, 52 and 72 weeks-old, were used to evaluate the desensitization process. Expression of α1 -adrenoceptor subtypes, endothelial NOS (eNOS) and neuronal NOS (nNOS) were determined in rat aorta and left ventricle (LV). Expression levels were also evaluated in LV of a group of heart failure patients with a wide age range. KEY RESULTS: Repeated application of phenylephrine decreased subsequent α1 -adrenoceptor-mediated vasoconstriction by increasing nNOS protein expression in aorta, but not in tail or mesenteric resistance arteries, where mRNA levels of nNOS were undetectable. This desensitization process disappeared in the absence of endothelium or in the presence of L-NAME (100 µM), nNOS inhibitors, SMTC (1 µM) and TRIM (100 µM), and 5-methylurapidil (100 nM, α1A -antagonist), but not BMY7378 (10 nM, α1D -antagonist). The α1A /nNOS-mediated desensitization was absent in aged SHR and Wistar animals, where the expression of α1A -adrenoceptors was reduced in aorta and LV. In human LV, a negative correlation was found between age and α1A -adrenoceptor expression. CONCLUSIONS AND IMPLICATIONS: The α1A -adrenoceptor subtype, through endothelial nNOS-derived NO, may act as a physiological 'brake' against the detrimental effects of excessive α1 -adrenoceptor-mediated vasoconstriction. Reduced α1A -adrenoceptor- and nNOS-mediated desensitization in aged patients could be involved in the age-dependent elevation of adrenergic activity.

[Impact of diabetes mellitus on heart transplant recipients]. / Impacto de la diabetes mellitus en el paciente con trasplante cardiaco.

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.