Cándido Martín-Luengo

Prognostic relations between inflammatory markers and mortality in diabetic patients with non-ST elevation acute coronary syndrome

Objective: To determine the differences in the inflammatory status between diabetic and non-diabetic patients and to evaluate the usefulness of C reactive protein, fibrinogen, and leucocyte count as predictors of death in diabetic patients with unstable coronary disease. Design: Nested case-control comparisons of the inflammatory status between diabetic and non-diabetic patients. Prospective cohort analysis of C reactive protein concentration, fibrinogen concentration, and leucocyte count as predictors of cardiovascular death in diabetic patients. Setting: Coronary care unit in Spain. Participants: 83 diabetic patients with non-ST elevation acute coronary syndrome and 83 sex and aged matched patients selected from 361 non-diabetic patients with non-ST elevation acute coronary syndrome. Main outcome measures: Plasma concentrations of C reactive protein and fibrinogen, and leucocyte count. Investigators contacted patients to assess clinical events. Results: Concentrations of C reactive protein and fibrinogen, and leucocyte count on admission were higher in diabetic than in non-diabetic patients (7 mg/l v 5 mg/l, p  =  0.020; 3.34 g/l v 2.90 g/l, p  =  0.013; and 8.8 × 109/l v 7.8 × 109/l, p  =  0.040). Among diabetic patients, these values were also higher in those who died during the 22 month follow up (13 mg/l v 6 mg/l, p  =  0.001; 3.95 g/l v 3.05 g/l, p < 0.001; and 11.4 × 109/l v 8.4 × 109/l, p  =  0.005). After adjustment for confounding factors, diabetic patients in the highest tertile of C reactive protein had a hazard ratio for cardiovascular death of 4.51 (95% confidence interval (CI) 1.62 to 12.55). Similar hazard ratios were for fibrinogen 3.74 (95% CI 1.32 to 10.62) and for leucocyte count 3.64 (95% CI 1.37 to 9.68). Conclusions: Inflammation appears more evident in diabetic than in non-diabetic patients with acute coronary syndrome. C reactive protein concentration, fibrinogen concentration, and leucocyte count constitute independent predictors of cardiovascular death in diabetics with unstable coronary disease.

Association between self-replicating calcifying nanoparticles and aortic stenosis: a possible link to valve calcification.

AIMS Among various hypotheses proposed for pathological tissue calcification, recent evidence supports the possibility that self-replicating calcifying nanoparticles (CNPs) can contribute to such calcification. These CNPs have been detected and isolated from calcified human tissues, including blood vessels and kidney stones, and are referred to as nanobacteria. We evaluated calcific aortic valves for the presence of CNP. METHODS AND RESULTS Calcific aortic valves were obtained from 75 patients undergoing surgical valve replacement. The control group was formed by eight aortic valves corresponding to patients with heart transplants. In the microbiology laboratory, valves were screened for CNP using a 4-6 weeks specific culture method. The culture for CNP was positive in 48 of the 75 valves with aortic stenosis (64.0%) in comparison with zero of eight (0%) for the control group (P = 0.0005). The observation of cultures by way of scanning electron microscopy highlighted the resemblance in size and morphology of CNP. CONCLUSION Self-replicating calcific nanometer-scale particles, similar to those described as CNP from other calcific human tissues, can be cultured and visualized from calcific human aortic valves. This finding raises the question as to whether CNP contribute to the pathogenesis of the disease or whether they are only innocent bystanders.

Identification of serum endoglin as a novel prognostic marker after acute myocardial infarction.

Endoglin is a proliferation‐associated and hypoxia‐inducible protein expressed in endothelial cells. The levels of soluble circulating endoglin and their prognostic significance in patients with acute myocardial infarction (AMI) are not known. In this observational prospective study serum endoglin levels were measured by ELISA in 183 AMI patients upon admission to hospital and 48 hrs later and in 72 healthy controls. Endoglin levels in AMI patients on admission were significantly lower than in healthy controls (4.25 ± 0.99 ng/ml versus 4.59 ± 0.87 ng/ml; P= 0.013), and decreased further in the first 48 hours (3.65 ± 0.76 ng/ml, P < 0.001). Upon follow‐up (median 319 days), patients who died had a significantly greater decrease in serum endoglin level over the first 48 hrs than those who survived (1.03 ± 0.91 versus 0.54 ± 0.55 ng/ml; P= 0.025). Endoglin decrease was an independent predictor of short‐term (30 days) (hazard ratio 2.33;95% CI = 1.27–4.23; P= 0.006) cardiovascular mortality, and also predicts overall cardiovascular mortality during the follow‐up (median 319 days) in AMI patients (hazard ratio 2.13;95% CI = 1.20–3.78; P= 0.01). In conclusion, early changes in serum endoglin may predict mortality after AMI.

Significance of the learning curve in left atrial appendage occlusion with two different devices

To evaluate the impact of learning on outcome with use of two different left atrial appendage (LAA) occlusion devices.

Association between -T786C NOS3 polymorphism and resistant hypertension: a prospective cohort study

BackgroundIt is estimated that 5% of the hypertensive patients are resistant to conventional antihypertensive therapy. Polymorphisms in the endothelial nitric oxide synthase (NOS3) gene have been associated with high blood pressure levels, but not with resistant hypertension. The aim of the present study was to investigate if the -786T>C and G894T (Glu298Asp) polymorphisms of the NOS3 gene were associated with resistant hypertension.MethodsA prospective case-control observational study was performed. From a series of 950 consecutive patients followed up during 42 months, 48 patients with resistant hypertension were detected. 232 patients with controlled high blood pressure were also included.ResultsNo differences were observed in the distribution of G894T (Glu298Asp) NOS3 genotypes between the resistant hypertension group and the controlled hypertension patients. However, genotype -786CC was more frequent in the group of patients with resistant hypertension (33.3%) than in the group of patients with controlled high blood pressure (17.7%) (p 0.03). Furthermore carriers of allele T (-786TC and -786TT) were more frequent in patients with controlled hypertension (82.3%) than those with resistant hypertension (66.7%) (Multivariate analysis; RR 2.09; 95% CI 1.03–4.24; p 0.004).ConclusionOur results indicate that genotype -786CC of the NOS3 gene increase the susceptibility to suffer resistant hypertension, which suggest that resistance to conventional therapy could be determined at the endothelial level.

[Kinetics of C-reactive protein release in different forms of acute coronary syndrome].

INTRODUCTION AND OBJECTIVES Better knowledge of C-reactive protein (CRP) kinetics could lead to improved clinical application of this biomarker. METHODS We studied 110 patients: 42 had ST-elevation acute myocardial infarction (STEMI), 35 had non-ST-elevation acute myocardial infarction (NSTEMI), and 33 had unstable angina. Patients were admitted to our institution within 6 hours of symptom onset. The levels of CRP, troponin-I, and creatine kinase MB fraction (CK-MB) were measured on admission and every 6 hours during the first 48 h. The CRP level was also measured daily until hospital discharge. RESULTS The median (interquartile range) CRP level increased relative to baseline from 6 hours after admission, from 5 (2-9) mg/L to 6 (3-10) mg/L (P=.004). Although, CRP levels on admission were similar in all groups, there was a significant difference in peak CRP level: it was 67 (36-112) mg/L in the STEMI group, 29 (20-87) mg/L in the NSTEMI group, and 18 (12-36) mg/L in the unstable angina group. The maximum CRP level was observed 49 (38-53) hours after the onset of symptoms, but occurred later in patients with STEMI. Although there was only a weak non-significant correlation between CRP and troponin levels (r=0.135) at admission, the maximum CRP level was found to be influenced by the degree of myocardial damage (r=0.496; P< .001). CONCLUSIONS The pattern of CRP release observed was clearly different in different forms of acute coronary syndrome. Although the CRP level measured at admission was similar in all patient groups, it was influenced by the degree of early myocardial tissue necrosis. This variation in CRP kinetics should be taken into consideration when designing future studies.

Influence of beta-blocker therapy on antitachycardia pacing effectiveness for monomorphic ventricular tachycardias occurring in implantable cardioverter-defibrillator patients: a dose-dependent effect

AIMS To determine, in a non-selected population of 282 implantable cardioverter-defibrillator (ICD) patients with left ventricular dysfunction, the influence of the dose of beta-blockers on antitachycardia pacing (ATP) effectiveness and on the incidence of shock due to monomorphic ventricular tachycardias (VT). METHODS AND RESULTS We followed 282 ICD patients along 26 +/- 19 months. Antitachycardia pacing and shock programming were standardized. We determined the indexed dose equivalent of beta-blockers (IDE-BB), using metoprolol as a reference, at each VT presentation. The median of IDE-BB was 55 mg/m(2)/day. We analysed 846 VT occurred in 100 patients. The ATP success rate was 84%. Upon classification of the events into three groups (IDE-BB = 0, IDE-BB < 55, and IDE-BB > or = 55), the frequency of effective ATP increased with the IDE-BB: 75 vs. 83 vs. 92% (P < 0.001). According to logistic regression, IDE-BB remained as an independent predictor of effective ATP (P < 0.001) and VT-related shock (P = 0.001). Both the mean ATP effectiveness per patient (67 vs. 80 vs. 91%, P = 0.007) and the mean survival time free of VT-related shock (583 vs. 847 vs. 1158 days, P = 0.019, log-rank test) increased linearly with the dose of beta-blockers. CONCLUSION Beta-blockers increase the effectiveness of ATP through a dose-dependent effect. As a result, they reduce the incidence of shocks due to VT.

Pronóstico hospitalario del síndrome coronario agudo sin elevación del segmento ST determinado por una nueva escala de riesgo integrada por variables electrocardiográficas obtenidas al ingreso

Diferentes variables electrocardiograficas tienen capacidad predictiva en el sindrome coronario agudo sin elevacion del ST (SCASEST). Tras analizar a 427 pacientes, construimos una escala de riesgo (ER) basada en el ECG al ingreso (ER-ECG) para definir la probabilidad de muerte o isquemia recurrente (M-IsqR) durante la hospitalizacion, que fue del 36%. En un analisis de regresion logistica que incluyo siete variables electrocardiograficas y las de la ER TIMI, alcanzaron la significacion estadistica: QTc ≥ 450 ms (odds ratio [OR] = 4,2; p 0,5 (OR = 2,7; p 0,5 mm y 1 a crecimiento auricular izquierdo. Agrupando a los pacientes segun la ER-ECG en: ≤ 1, 2-3, ≤ 4, esta discrimino adecuadamente la probabilidad de M-IsqR: el 11 frente al 27 frente al 58% (p

Early Reduction of QT Dispersion after Primary Percutaneous Intervention in ST-Segment Elevation Acute Myocardial Infarction

Objectives: To determine, in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PPCI), the mechanisms and clinical implications of the acute changes in QT dispersion (QTd). Methods: In this prospective study we included 216 patients admitted with a STEMI of <12 h of evolution. All were treated with PPCI. QTd was measured prior to PPCI and within 1 h after. Results: The ratio of QTd reduction after PPCI (QTd-R) – defined as [(QTd before PPCI – QTd after PPCI)/QTd before PPCI] ×100 – was significantly correlated with the percentage of ST-segment elevation resolution (ST-R; p < 0.001). To determine the significance of the different values of QTd-R, we further subdivided our population into 3 groups according to the tertiles of QTd-R (<10, 11–49, ≥50%). Patients with longer QTd-R had higher percentages of ST-R: 32 ± 43 for QTd-R <10% vs. 60 ± 21 for 11–49% vs. 71 ± 12 for ≥50% (p < 0.05). By logistic regression, patients with QTd-R ≥50% had a reduction of 75% in the adjusted frequency of death or severe heart failure during hospitalization (95% CI 13–73%, p = 0.03). Conclusion: QTd-R after PPCI occurs early, is closely related to the restoration of reperfusion at the microvascular level and provides additional prognostic information.

Influence of cycle length variations on antitachycardia pacing effectiveness among ICD patients

BACKGROUND Antitachycardia pacing (ATP) fails to terminate 5% to 25% of ventricular tachycardias (VTs) occurring in implantable cardioverter-defibrillator patients. We speculated that small fluctuations in VT cycle length (CL) may be related to the efficacy of subsequent ATP. OBJECTIVE The purpose of this study was to determine the relationship between the R-R variations of the last 12 R-R intervals before ATP and the efficacy of the first ATP attempt. METHODS We studied 551 VTs (CL 329±35 ms) occurring in 67 patients. We also analyzed the percentage of variation (P-RR), which was calculated by dividing the mean difference between each R-R interval and the next one by the CL (×100), and the acceleration index (AI), which was calculated by dividing the CL of the first 6 R-R intervals by the CL of the next 6. RESULTS The effectiveness of the first ATP therapy was 81%, being higher in VTs with AI<1 (85% vs 64%; P<.001). After classifying the events according to the tertiles of P-RR, ATP efficiency was better in higher values of P-RR (VTs with AI<1): 99% (third tertile) vs 85% (second tertile) vs 76% (first tertile), P<.001; and for VTs with AI≥1: 94% vs 68% vs 42% (P<.001). By logistic regression, P-RR (%; odds ratio 2.37; P<.001), and AI<1 (odds ratio 4.17; P<.001) were found to be independent predictors of successful first ATP attempts. CONCLUSION Small changes in CL increase the effectiveness of ATP significantly. VTs with lower degrees of R-R fluctuations, especially when the pattern is a progressive CL shortening, are infrequently terminated by ATP.