Mobilization of endothelial progenitor cells in acute cardiovascular events in the PROCELL study: time-course after acute myocardial infarction and stroke.

The mobilization pattern and functionality of endothelial progenitor cells after an acute ischemic event remain largely unknown. The aim of our study was to characterize and compare the short- and long-term mobilization of endothelial progenitor cells and circulating endothelial cells after acute myocardial infarction or atherothrombotic stroke, and to determine the relationship between these cell counts and plasma concentrations of vascular cell adhesion molecule (VCAM-1) and Von Willebrand factor (VWF) as surrogate markers of endothelial damage and inflammation. In addition, we assessed whether endothelial progenitor cells behave like functional endothelial cells. We included 150 patients with acute myocardial infarction or atherothrombotic stroke and 145 controls. Endothelial progenitor cells [CD45-, CD34+, KDR+, CD133+], circulating endothelial cells [CD45-, CD146+, CD31+], VWF, and VCAM-1 levels were measured in controls (baseline only) and in patients within 24h (baseline) and at 7, 30, and 180 days after the event. Myocardial infarction patients had higher counts of endothelial progenitor cells and circulating endothelial cells than the controls (201.0/mL vs. 57.0/mL; p<0.01 and 181.0/mL vs. 62.0/mL; p<0.01). Endothelial progenitor cells peaked at 30 days post-infarction (201.0/mL vs. 369.5/mL; p<0.01), as did VCAM-1 (573.7 ng/mL vs. 701.8 ng/mL; p<0.01). At 180 days post-infarction, circulating endothelial cells and VWF decreased, compared to baseline. In stroke patients, the number of endothelial progenitor cells - but not circulating endothelial cells - was higher than in controls (90.0/mL vs. 37.0/mL; p=0.01; 105.0/mL vs. 71.0/mL; p=0.11). At 30 days after stroke, however, VCAM-1 peaked (628.1/mL vs. 869.1/mL; p<0.01) but there was no significant change in endothelial progenitor cells (90/mL vs. 78/mL; p<0.34). At 180 days after stroke, circulating endothelial cells and VWF decreased, compared to baseline. Cultured endothelial progenitor cells from controls and myocardial infarction patients had endothelial phenotype characteristics and exhibited functional differences in adhesion and Ca(2+) influx, but not in proliferation and vasculogenesis. In myocardial infarction patients, VCAM-1 levels and mobilization of endothelial progenitor cells peaked at 30 days after the ischemic event. Although a similar VCAM-1 kinetic was observed in stroke patients, endothelial progenitor cells did not increase. Endothelial progenitor cells had mature endothelial capabilities in vitro.

The efficacy of ticagrelor is maintained in women with acute coronary syndromes participating in the prospective, randomized, PLATelet inhibition and patient Outcomes (PLATO) trial.

AIMS: The aim of this study was to assess the relationship between sex and clinical outcomes and treatment-related complications in patients with ST-elevation or non-ST-elevation acute coronary syndromes (ACS) randomized to treatment with ticagrelor or clopidogrel in the PLATelet inhibition and patient Outcomes (PLATO) trial. METHODS: The associations between sex subgroup and the primary composite outcomes, secondary outcomes, and major bleeding endpoints as well as interaction of sex subgroup with treatment effects were analysed using Cox proportional-hazards models. RESULTS: Sex was not significantly associated with the probability of the primary composite endpoint [adjusted hazard ratio (HR): 1.02 (0.91-1.16)], or other adverse cardiovascular endpoints. Ticagrelor was similarly more effective than clopidogrel in reducing rates of the primary endpoint in women 11.2 vs. 13.2% [adjusted HR: 0.88 (0.74-1.06)] and men 9.4 vs. 11.1% [adjusted HR: 0.86 (0.76-0.97)] (interaction P-value 0.78), all-cause death in women 5.8 vs. 6.8% [adjusted HR: 0.90 (0.69-1.16)] and men 4.0 vs. 5.7% [adjusted HR: 0.80 (0.67-0.96)] (interaction P-value 0.49), and definite stent thrombosis in women 1.2 vs. 1.4% [adjusted HR: 0.71 (0.36-1.38)] and men 1.4 vs. 2.1% [adjusted HR: 0.63 (0.45-0.89)] (interaction P-value 0.78). The treatments did not differ for PLATO-defined overall major bleeding complications in women [adjusted HR: 1.01 (0.83-1.23)] or men [adjusted HR: 1.10 (0.98-1.24)]. Sex had no significant association with these outcomes (interactions P = 0.43-0.88). CONCLUSION: Female sex is not an independent risk factor for adverse clinical outcomes in moderate-to-high risk ACS patients. Ticagrelor has a similar efficacy and safety profile in men and women.

Allogeneic adipose stem cell therapy in acute myocardial infarction.

BACKGROUND: Stem cell therapy offers a promising approach to reduce the long-term mortality rate associated with heart failure after acute myocardial infarction (AMI). To date, in vivo translational studies have not yet fully studied the immune response to allogeneic adipose tissue-derived mesenchymal stem cells (ATMSCs). We analysed the immune response and the histological and functional effects of allogeneic ATMSCs in a porcine model of reperfused AMI and determine the effect of administration timing. DESIGN: Pigs that survived AMI (24/26) received intracoronary administration of culture medium after reperfusion (n = 6), ATMSCs after reperfusion (n = 6), culture medium 7 days after AMI (n = 6) or ATMSCs 7 days after AMI (n = 6). At 3-week follow-up, cardiac function, alloantibodies and histological analysis were evaluated. RESULTS: Administration of ATMSCs after reperfusion and 7 days after AMI resulted in similar rates of cell engraftment; some of those cells expressed endothelial, smooth muscle and cardiomyogenic cell lineage markers. Delivery of ATMSCs after reperfusion compared with that performed at 7 days was more effective in increasing: vascular density (249 ± 64 vs. 161 ± 37 vessels/mm2; P < 0.01), T lymphocytes (1 ± 0.4 vs. 0.4 ± 0.3% of area CD3(+) ; P < 0.05) and expression of vascular endothelial growth factor (VEGF; 32 ± 7% vs. 20 ± 4% of area VEGF(+) ; P < 0.01). Allogeneic ATMSC-based therapy did not change ejection fraction but generated alloantibodies. CONCLUSIONS: The present study is the first to demonstrate that allogeneic ATMSCs elicit an immune response and, when administered immediately after reperfusion, are more effective in increasing VEGF expression and neovascularization.

Lung function abnormalities are highly frequent in patients with heart failure and preserved ejection fraction.

BACKGROUND: Heart failure with preserved ejection fraction (HFPEF) is the most prevalent form of heart failure in outpatients. Yet, the pathophysiology of this syndrome is unclear and pharmacological treatment does not improve prognosis. Because breathlessness during activities of daily living is the most frequent complaint of patients with HFPEF, we hypothesised that lung function may be often abnormal in these patients due to either a direct effect of HFPEF and/or shared risk factors. In this study we explore the frequency, type and severity of lung function abnormalities in HFPEF. METHODS: We measured forced spirometry, static lung volumes, pulmonary diffusing capacity (DL(CO)) and arterial blood gases in 69 outpatients with newly diagnosed symptomatic HFPEF. RESULTS: We found that 94% of the patients showed abnormalities in at least one of the lung function measurements obtained: spirometry was abnormal in 59%, DL(CO) in 83% and arterial hypoxaemia was present in 62%. Their severity varied between patients, they were more prevalent in patients with NYHA functional class III/IV, and most often they were undiagnosed and untreated. CONCLUSIONS: Lung function abnormalities are very frequent in HFPEF patients. A greater awareness among clinicians may contribute to improve their management and health status.

An affordable method to obtain cultured endothelial cells from peripheral blood.

The culture of endothelial progenitor cells (EPC) provides an excellent tool to research on EPC biology and vascular regeneration and vasculogenesis. The use of different protocols to obtain EPC cultures makes it difficult to obtain comparable results in different groups. This work offers a systematic comparison of the main variables of most commonly used protocols for EPC isolation, culture and functional evaluation. Peripheral blood samples from healthy individuals were recovered and mononuclear cells were cultured. Different recovery and culture conditions were tested: blood volume, blood anticoagulant, coating matrix and percentage of foetal bovine serum (FBS) in culture media. The success of culture procedure, first colonies of endothelial cells appearance time, correlation with number of circulating EPC (cEPC) and functional comparison with human umbilical vein endothelial cells (HUVEC) were studied. The use of heparin, a minimum blood volume of 30 ml, fibronectin as a coating matrix and endothelial growing media-2 supplemented with 20% FBS increased the success of obtaining EPC cultures up to 80% of the processed samples while reducing EPC colony appearance mean time to a minimum of 13 days. Blood samples exhibiting higher cEPC numbers resulted in reduced EPC colony appearance mean time. Cells isolated by using this combination were endothelial cell-like EPCs morphological and phenotypically. Functionally, cultured EPC showed decreased growing and vasculogenic capacity when compared to HUVEC. Thus, above-mentioned conditions allow the isolation and culture of EPC with smaller blood volumes and shorter times than currently used protocols.

Effects of estrogen on vascular inflammation: a matter of timing.

OBJECTIVE: Our study aims to determine the role of time of menopause on vascular inflammation biomarkers and how it affects their modulation by estrogen and raloxifene in postmenopausal women. METHODS AND RESULTS: Uterine arteries from 68 postmenopausal women were divided into 3 segments and cultured for 24 hours in tissue culture media containing 17ß-estradiol (100 nmol/L), raloxifene (100 nmol/L), or vehicle. Assessment of arterial concentration of 13 inflammatory biomarkers was performed by multiplex immunobead-based assay. Aging per se has a positive correlation with the generation of several proinflammatory markers. Although short-term estradiol exposure correlates with lower expression of tumor necrosis factor-α, vascular endothelial growth factor, and interleukin-1ß in all age groups, for most biomarkers aging was associated with a switch from a beneficial anti-inflammatory action by estrogen, at earlier stages of menopause, to a proinflammatory profile after 5 years past its onset. Raloxifene has no significant effect on the expression of all proinflammatory markers. Western blot analysis of estrogen receptor expression (estrogen receptor-α and estrogen receptor-ß) showed that estrogen receptor-ß increases with aging, and this increase has a positive correlation with the generation of several proinflammatory markers. CONCLUSIONS: Aging alters estrogen-mediated effects on the modulation of inflammatory biomarkers in women. How aging affects estrogen responses on vascular inflammation is not clear, but our data show a positive association between increased estrogen receptor-ß expression with aging and proinflammatory effects by estrogen.

[Diagnosis of heart failure with preserved or reduced ejection fraction in a one-stop clinic]. / Diagnóstico de la insuficiencia cardíaca con fracción de eyección preservada o reducida mediante una consulta de alta resolución.

OBJECTIVES: a) To assess the usefulness of a one-stop clinic for the diagnosis of outpatients with new onset heart failure; b) to characterize these patients comparing preserved (HF-PEF) versus reduced ejection fraction (HF-REF), and c) to determine brain natriuretic peptide (BNP) cut-off limit to identify HF in outpatients. DESIGN: Observational descriptive study. SETTING: Primary care. PARTICIPANTS AND MEASUREMENTS: A total of 143 outpatients with new onset HF were assessed in a one-stop clinic. A cardiologist evaluation, electrocardiogram, chest X-ray, BNP, and echocardiography (diastolic and systolic study) were performed. RESULTS: Almost two-thirds (65.7%) were diagnosed with HF: 67% with HF-PEF and 33% HF-REF. Women (71.4% versus 38.7%, P=.002), presence of swelling ankles (61.9% versus 35.5%, P=.016) and higher body mass index (29.8±5.1 versus 27.2±5.0 P=.021) were more frequent in the first group of patients. Echocardiographic signs of diastolic dysfunction and pulmonary hypertension were found in both groups, with higher values of BNP (153.3±123.1 versus 400.8±579.8 P=.025) and troponin I (0.024±0.019 versus 0.071±0.12, P=.037) in HF-REF patients. Female gender and swelling ankles were predictors of HF-PEF in the multivariate analysis, while Q waves and higher values of BNP and heart rate were predictors of HF-REF. A cut-off value of 60.12 pg/ml for BNP provided 83% sensitivity, 84% specificity (AUC=0.898; 95% CI; 0.848-0.948; P <.001). CONCLUSIONS: The one-stop HF clinic has diagnosed and characterized outpatients with new onset HF and high prevalence of HF-PEF. The cut-off value of 60.12 pg/ml for BNP provides high sensitivity and specificity to identify HF in this population.

Primary angioplasty vs. fibrinolysis in very old patients with acute myocardial infarction: TRIANA (TRatamiento del Infarto Agudo de miocardio eN Ancianos) randomized trial and pooled analysis with previous studies.

AIMS: To compare primary percutaneous coronary intervention (pPCI) and fibrinolysis in very old patients with ST-segment elevation myocardial infarction (STEMI), in whom head-to-head comparisons between both strategies are scarce. METHODS AND RESULTS: Patients ≥75 years old with STEMI <6 h were randomized to pPCI or fibrinolysis. The primary endpoint was a composite of all-cause mortality, re-infarction, or disabling stroke at 30 days. The trial was prematurely stopped due to slow recruitment after enrolling 266 patients (134 allocated to pPCI and 132 to fibrinolysis). Both groups were well balanced in baseline characteristics. Mean age was 81 years. The primary endpoint was reached in 25 patients in the pPCI group (18.9%) and 34 (25.4%) in the fibrinolysis arm [odds ratio (OR), 0.69; 95% confidence interval (CI) 0.38-1.23; P = 0.21]. Similarly, non-significant reductions were found in death (13.6 vs. 17.2%, P = 0.43), re-infarction (5.3 vs. 8.2%, P = 0.35), or disabling stroke (0.8 vs. 3.0%, P = 0.18). Recurrent ischaemia was less common in pPCI-treated patients (0.8 vs. 9.7%, P< 0.001). No differences were found in major bleeds. A pooled analysis with the two previous reperfusion trials performed in older patients showed an advantage of pPCI over fibrinolysis in reducing death, re-infarction, or stroke at 30 days (OR, 0.64; 95% CI 0.45-0.91). CONCLUSION: Primary PCI seems to be the best reperfusion therapy for STEMI even for the oldest patients. Early contemporary fibrinolytic therapy may be a safe alternative to pPCI in the elderly when this is not available.

Myocardial deformation analysis in Chagas heart disease with the use of speckle tracking echocardiography.

BACKGROUND: Assessment of myocardial deformation in Chagas disease may help us to better understand the disease pathophysiology and to detect early myocardial involvement. We aimed to characterize myocardial deformation in patients in different forms of Chagas disease and, specifically, assess differences between patients in the indeterminate form and controls. METHODS AND RESULTS: Speckle tracking echocardiography was performed in 98 subjects (22 with Chagas cardiomyopathy, 32 in the indeterminate form, and 44 control subjects) to quantify global and segmental left ventricular (LV) radial strain (RS), circumferential strain (CS), and longitudinal strain (LS). In a subset of patients from the indeterminate and control groups (n = 25), LV peak systolic twist and untwisting velocities were additionally assessed. Global RS, CS, and LS showed a significant decreasing trend across groups. Patients in the indeterminate form had significantly lower global RS and RS in the midinferior segment (median 39.8% vs 49.3% [P = .046] and 44.0% vs 56.0% [P = .038], respectively) and lower twist and untwisting velocity (P < .05 for both) compared with control subjects. CONCLUSION: Evaluation of myocardial deformation, particularly of RS, appears to be a sensitive technique for detection of myocardial involvement in patients in the indeterminate form and provides insights into the still unrevealed pathophysiology of Chagas heart involvement.

Endothelin-1 levels predict endothelial progenitor cell mobilization after acute myocardial infarction.

INTRODUCTION: Endothelin-1 (ET-1), circulating endothelial cells (CEC) and endothelial progenitor cells (EPC) are well-known modulators of endothelial function with important cardiac effects after an acute myocardial infarction. However, the relationship between them has never been assessed. The objective of the present study was to establish the relationship between ET-1, CEC, and EPC concentrations after ST-elevation myocardial infarction (STEMI). METHODS: Endothelin-1, CEC, and EPC levels were measured in 61 patients presenting with a first STEMI. Samples were withdrawn acutely 6-24h and 1week after admission. Assessments included reperfusion outcomes (angiography), left ventricular ejection fraction (echocardiography), and 30-day mortality. RESULTS: Mean age was 60.6±12.6years and 45 (74%) were males. Higher ET-1 plasma levels were associated with lower EPC count after 1week (7.45±2.53pg/ml if EPCs in the first quartile vs 5.72±1.49pg/ml if EPCs in the fourth quartile; P=0.04). In contrast with CEC and EPC count, higher ET-1 concentrations on admission were associated with Killip≥2 (9.92±2.01pg/ml vs 7.32±2.13pg/ml; P<0.001), post-reperfusion thrombolysis in myocardial infarction (TIMI) <3 (8.65±2.86pg/ml vs 5.87±1.93pg/ml; P=0.002), myocardial blush grade (MBG) <3 (7.46±2.48pg/ml vs 5.99±2.01pg/ml; P=0.004) and higher 30-day mortality (10.29±2.02pg/ml vs 6.57±2.20pg/ml; P=0.005). CONCLUSIONS: In STEMI patients, high ET-1 levels on admission predict a lower EPC mobilization after 1week. Endothelin-1 provides better clinical, angiographic and echocardiographic information for prognosis than do CEC and EPC concentrations.

Characterization of ion channels involved in the proliferative response of femoral artery smooth muscle cells.

OBJECTIVE: Vascular smooth muscle cells (VSMCs) contribute significantly to occlusive vascular diseases by virtue of their ability to switch to a noncontractile, migratory, and proliferating phenotype. Although the participation of ion channels in this phenotypic modulation (PM) has been described previously, changes in their expression are poorly defined because of their large molecular diversity. We obtained a global portrait of ion channel expression in contractile versus proliferating mouse femoral artery VSMCs, and explored the functional contribution to the PM of the most relevant changes that we observed. METHODS AND RESULTS: High-throughput real-time polymerase chain reaction of 87 ion channel genes was performed in 2 experimental paradigms: an in vivo model of endoluminal lesion and an in vitro model of cultured VSMCs obtained from explants. mRNA expression changes showed a good correlation between the 2 proliferative models, with only 2 genes, Kv1.3 and Kvbeta2, increasing their expression on proliferation. The functional characterization demonstrates that Kv1.3 currents increased in proliferating VSMC and that their selective blockade inhibits migration and proliferation. CONCLUSIONS: These findings establish the involvement of Kv1.3 channels in the PM of VSMCs, providing a new therapeutical target for the treatment of intimal hyperplasia.

Usefulness of pain presentation characteristics for predicting outcome in patients presenting to the hospital with chest pain of uncertain origin.

BACKGROUND: Decision making in chest pain of uncertain origin is challenging. OBJECTIVES: To evaluate the predictive value of simple characteristics of pain presentation in patients coming to the emergency department with chest pain and without electrocardiogram ischaemia or raised troponin. METHODS: 789 patients were studied. The following categorical pain characteristics were collected: effort related pain, pressing character, radiation, associated symptoms, and ≥ 2 episodes in 24 h. Additionally, a predefined semi-quantitative pain score including seven items (Geleijnse score) was completed. Risk factors and co-morbidities were also recorded. The primary and secondary endpoints were cardiac events at 30 days and at 1 year. RESULTS: After adjusting for risk factors and co-morbidites, the pain characteristics associated with the primary and secondary endpoints were effort related pain (HR=2.1, 95% CI 1.5 to 3.0, p=0.0001; HR=1.8, 95% CI 1.3 to 2.5, p=0.0003) and ≥ 2 episodes in 24 h (HR=2.4, 95% CI 1.7 to 3.5, p=0.0001; HR=2.3, 95% CI 1.7 to 3.2, p=0.0001). Both variables retained their predictive value in women, diabetics and elderly (>70 years) patients. The discriminatory capacity of the predictive models including these two pain characteristics for the primary and secondary endpoints (C-statistic 0.76 and 0.76) was better than using the complex semi-quantitative pain score (C-statistic 0.69 and 0.71). CONCLUSION: In patients presenting to the emergency department with chest pain and without electrocardiogram ischaemia or raised troponin, effort related pain and ≥ 2 episodes in 24 h are the main characteristics to be considered for decision making.

Randomized comparison between clinical evaluation plus N-terminal pro-B-type natriuretic peptide versus exercise testing for decision making in acute chest pain of uncertain origin.

BACKGROUND: Exercise testing constitutes the usual tool for decision making in chest pain units. This policy implies logistical constrains. Our aim was to evaluate a new strategy, combining a clinical risk score and N-terminal pro-B-type natriuretic peptide (NT-proBNP), in patients presenting to the emergency department with chest pain, without ischemic electrocardiogram changes or troponin elevation. METHODS: A total of 320 patients were randomized to either usual management, involving exercise testing, or a new strategy combining a clinical risk score and NT-proBNP without exercise testing. In the usual management, discharge decision was guided by the result of exercise test. In the new strategy, those patients with low clinical risk score and NT-proBNP were directly discharged. The primary outcome was hospitalization at the index episode. Secondary outcomes were cardiac events at 1 year. RESULTS: A total of 110 patients (69%) were hospitalized using usual management in comparison with 90 (56%) in the new strategy (P = .03). There were no differences in death or myocardial infarction (n = 11, 6.9% vs n = 6, 3.8%, P = .3) or cardiac events (n = 38, 24% vs n = 28, 18%, P = .2). Revascularizations at the index episode were more frequent under usual management (18% vs 8%, P = .01), although the new strategy was associated with higher rate of planned postdischarge revascularizations (0.6% vs 5%, P = .04). CONCLUSIONS: A strategy combining clinical history and NT-proBNP is simpler and reduced initial emergency hospitalizations in patients with chest pain, in comparison with the usual strategy involving exercise testing. Larger studies to assess its impact on long-term hard end points are needed.

"Do GRACE (Global Registry of Acute Coronary events) risk scores still maintain their performance for predicting mortality in the era of contemporary management of acute coronary syndromes?".

BACKGROUND: Although the GRACE risk scores (RS) are the preferred scoring system for risk stratification in acute coronary syndromes (ACS), little is known whether these RS still maintain their performance in the current era. We aimed to investigate this issue in a contemporary population with ACS. METHODS: The study population composed of patients enrolled in the MASCARA national registry. The GRACE RS were calculated for each patient. Discrimination and calibration were evaluated with the C statistic and the Hosmer-Lemeshow test, in the whole population and according to the type of ACS, risk strata, and whether the patient had a history of diabetes and/or chronic renal failure. We determined if left ventricular ejection fraction (LVEF) provides incremental prognostic information above that established by the RS and whether percutaneous coronary intervention (PCI) during admission affects the performance of the score for predicting 6-month mortality. RESULTS: The 5,985 patients constituted the validation cohort for the in-hospital mortality RS and 5,635 the validation cohort for the 6-month mortality RS. Overall, both GRACE RS demonstrated excellent discrimination (C > 0.80) and calibration (all P values in Hosmer-Lemeshow >.1). Although similar results were seen in all subgroups, the 6-month mortality RS performed significantly less well in patients undergoing PCI compared to those patients who did not (C = 0.73 vs 0.76, P < .004). Adding LVEF to the RS did not convey significant prognostic information. CONCLUSIONS: The GRACE RS for predicting in-hospital and 6-month mortality still maintain their excellent performance in a contemporary cohort of patients with ACS. Further studies are needed to investigate the performance of the 6-month mortality GRACE score in patients undergoing in-hospital PCI. Left ventricular ejection fraction did not convey significant information over that provided by the RS.

Effects of adipose tissue-derived stem cell therapy after myocardial infarction: impact of the route of administration.

BACKGROUND: Cell-based therapies offer a promising approach to reducing the short-term mortality rate associated with heart failure after a myocardial infarction. The aim of the study was to analyze histological and functional effects of adipose tissue-derived stem cells (ADSCs) after myocardial infarction and compare 2 types of administration pathways. METHODS AND RESULTS: ADSCs from 28 pigs were labeled by transfection. Animals that survived myocardial infarction (n = 19) received: intracoronary culture media (n = 4); intracoronary ADSCs (n = 5); transendocardial culture media (n = 4); or transendocardial ADSCs (n = 6). At 3 weeks' follow-up, intracoronary and transendocardial administration of ADSCs resulted in similar rates of engrafted cells (0.85 [0.19-1.97] versus 2 [1-2] labeled cells/cm(2), respectively; P = NS) and some of those cells expressed smooth muscle cell markers. The intracoronary administration of ADSCs was more effective in increasing the number of small vessels than transendocardial administration (223 +/- 40 versus 168 +/- 35 vessels/mm(2); P < .05). Ejection fraction was not modified by stem cell therapy. CONCLUSIONS: This is the first study to compare intracoronary and transendocardial administration of autologous ADSCs in a porcine model of myocardial infarction. Both pathways of ADSCs delivery are feasible, producing a similar number of engrafted and differentiated cells, although intracoronary administration was more effective in increasing neovascularization.

Preparation for pacemaker or implantable cardiac defibrillator implants in patients with high risk of thrombo-embolic events: oral anticoagulation or bridging with intravenous heparin? A prospective randomized trial.

AIMS: Current guidelines recommend stopping oral anticoagulation (OAC) and starting heparin infusion before implanting/replacing a pacemaker/implantable cardioverter-defibrillator (ICD) in patients with high risk for thrombo-embolic events. The aim of this study was to demonstrate that the maintenance of OAC during device implantation/replacement is as safe as bridging to intravenous heparin and shortens in-hospital stay. METHODS AND RESULTS: A cohort of 101 consecutive patients with high risk for embolic events and indication for implant/replacement of a pacemaker/ICD were randomized to two anticoagulant strategies: bridging from OAC to heparin infusion (n = 51) vs. maintenance of OAC to reach an INR = 2 +/- 0.3 at the day of the procedure (n = 50). Haemorrhagic and thrombo-embolic complications were evaluated at discharge, 15 and 45 days after the procedure. A total of 4/51 patients (7.8%) from heparin group and 4/50 (8.0%) from the OAC group developed pocket haematoma following the implant (P = 1.00). One haematoma in each group required evacuation (1.9 vs. 2%, P = 1.00). No other haemorrhagic events or embolic complications developed during the follow-up. Duration of the hospital stay was longer in the heparin group [median of 5 (4-7) vs. 2 (1-4) days; P < 0.001]. CONCLUSION: Implant of devices maintaining OAC is as safe as bridging to heparin infusion and allows a significant reduction of in-hospital stay.

[III Catalan registry of ST elevation acute myocardial infarction. Comparison with former Catalan registries I and II from Catalonia, Spain]. / Resultados del III registro IAM CAT de pacientes con infarto de miocardio con elevación del segmento ST en Cataluña. Comparación con los registros IAM CAT I y II.

BACKGROUND AND OBJECTIVE: To analyze the use of reperfusion therapy in patients with ST elevation myocardial infarction (STEMI) in Catalonia in a registry performed in 2006 (IAM CAT III) and its comparison with 2 previous registries PATIENTS AND METHODS: Frequency of reperfusion therapy and time intervals between symptom onset - reperfusion therapy were the principal variables investigated. The IAM CAT I (June-December 2000) included 1,450 patients, the IAM CAT II (October 2002-April 2003) 1,386, and the IAM CAT III (October-December 2006) 367. RESULTS: The proportion of patients treated with reperfusion increased progressively (72%, 79% and 81%) as the use of primary angioplasty (5%, 10% and 33%). In the III registry the transfer system most frequently used was the SEM/061 (17%, 32% and 47%, respectively) but the time interval symptom onset-first contact with the medical system did not improve (II, 90 vs III, 105 min), the interval symptom onset-thrombolytic therapy did hardly change (178, 165 and 177 min) and the interval hospital arrival-trombolysis (needle-door) tended to improve (59, 42 and 42 min). Thirty day mortality in STEMI patients declined progressively through the 3 registries (12.1, 10.6 and 7.4%, p=0.012). CONCLUSIONS: The proportion of STEMI patients treated with reperfusion has improved but the interval to its application has not been shortened. To improve the latter it is mandatory an earlier contact with the medical system, a shortening of the intervals door-needle and door-balloon through better coordination between the 061, the sanitary personnel and the hospital administration, and to consider the subject as a real sanitary priority.

Patterns of use and effectiveness of early invasive strategy in non-ST-segment elevation acute coronary syndromes: an assessment by propensity score.

BACKGROUND: The patterns of use and the benefit of an early invasive strategy (EIS) in patients with non-ST-segment elevation acute coronary syndrome in a real-life population are not well established. METHODS: All consecutive patients hospitalized because of non-ST-segment elevation acute coronary syndrome between November 2004 and June 2005 in 32 randomly selected hospitals were prospectively included. Patients were stratified by their baseline risk profile using the Global Registry of Acute Coronary Events (GRACE) risk score in 2 groups. Inhospital mortality and 1- and 6-month mortality or rehospitalization for acute coronary syndromes were analyzed. To ensure optimal adjustment propensity score, conventional logistic regression and Cox regression were used. RESULTS: Of 2,856 patients analyzed, 1,616 (56%) had low/intermediate risk (GRACE140). Patients who underwent EIS had lower risk than those who did not (GRACE score 128.2+/-41 vs 138.5+/-43, P<.001). Coronary angiography facility emerged as the strongest predictor of EIS (odds ratio [OR] 13.7 [95% CI 7.1-25]). Patients who underwent EIS had lower rate of the 6-month outcome in both the whole population (9% [95% CI 6.6-11.9] vs 14% [95% CI 12.5-15.6], P=.003) and in high-risk patients (16.5% [95% CI 11-23] vs 23.6% [95% CI 20.8-26.5], P=.04). However, this benefit of EIS was not apparent after statistical adjustment in the whole population (OR 0.8, CI 0.55-1.1, P=.17) or in high-risk patients (OR 0.7, CI 0.46-1.1, P=.16). CONCLUSIONS: In a real-life population, EIS was mainly performed in patients of low/intermediate risk. An obvious benefit of this strategy could not be found.

Genetic variation in the KCNMA1 potassium channel alpha subunit as risk factor for severe essential hypertension and myocardial infarction.

OBJECTIVE: The large conductance Ca2+ -dependent potassium channel plays a critical role in the control of vascular tone, coupling local increases in intracellular Ca2+ to membrane hyperpolarization and vascular relaxation. It also impacts blood pressure by modulating the renin-angiotensin-aldosterone system. Previous studies have shown that a polymorphism in the beta1 regulatory subunit of the Ca2+ -dependent potassium channel modulates the risk of diastolic hypertension in humans. METHODS: We have studied polymorphisms in the pore-forming alpha subunit gene (KCNMA1) and their association to hypertension and myocardial infarction. RESULTS: Sequencing of the KCNMA1 gene revealed two genetic variants (polymorphisms C864T and IVS17) in population-based epidemiological studies (4786 participants). We detected a significant increase in the frequency of the IVS17+37T>C polymorphism with severe systolic hypertension (48.3% for normotensive vs. 69% for severe systolic hypertension, P=0.03) and with severe general hypertension (48.7 vs. 65.8%, P=0.04), although the adjusted odd ratios did not reach statistical significance. Four C864T/IVS17 haplotypes were identified. Haplotype 4 (encompassing the C allele of the IVS17 polymorphism and the T allele of the C864T polymorphism) was related with increased severity of systolic and general hypertension as well as increased risk of myocardial infarction. CONCLUSION: Our study provides genetic evidence that highlights the relevance of the Ca2+ -dependent potassium channel in the control of human blood pressure and its impact on cardiovascular disease.

[Intensive insulin therapy in non-diabetic patients with myocardial infarction and hyperglycemia. INSUCOR study]. / Tratamiento intensivo con insulina en pacientes sin diabetes conocida con infarto de miocardio e hiperglucemia. Estudio INSUCOR.

BACKGROUND AND OBJECTIVE: Hyperglycemia at admission has been associated with bad prognosis in patients with myocardial infarction (MI). The clinical benefit of intensive insulin treatment has been evaluated in diabetic patients admitted to intensive care units. The aim of our study was to assess the short-term effects and the safety of strict glycemic control in subjects with MI and hyperglycemia without a previous history of diabetes. PATIENTS AND METHOD: Twenty-eight non-previously diabetic patients admitted with MI and hyperglycemia were randomized to 2 treatment arms during the first 48 h: a) the intensive group (n = 13) received intravenous insulin with target glycemia levels of 80-110 mg/dl, and b) the conventional group (n = 15) received subcutaneous insulin only when glycemia was 160 mg/dl. High-sensitivity C-reactive protein was determined at 48 h and before discharge. An oral glucose tolerance test was performed after one month. RESULTS: During the first 48 h, glycemia was significantly lower in the intensive than in the conventional group -mean (standard deviation): 104 (8) and 153 (54) mg/dl, respectively (p = 0.002)-, without any clinically significant hypoglycemic episodes. At 48 h, high-sensitivity C-reactive protein was significantly lower in the intensive group -44.3 (35.7) and 20.3 (20.3) mg/ml, respectively (p = 0.04)-. After 4 weeks, only 28.6% of patients showed normal response in the oral glucose tolerance test. CONCLUSIONS: Intensive treatment with insulin to maintain near normoglycemia in non-diabetic patients with MI and hyperglycemia is feasible, safe and more effective than conventional treatment. In addition, it produces attenuation of inflammatory response. Our study also confirms the high prevalence of unknown abnormalities in glucose tolerance in subjects with MI.