A case-control study of melatonin receptor type 1A polymorphism and acute myocardial infarction in a Spanish population.

Coronary artery disease (CAD) is a complex disease with genetic and environmental determinants. Although a large number of genetic polymorphisms involved in the pathogenesis of atherosclerosis have been identified, there is still no evidence of a genetic association with CAD. As melatonin might play a role in the pathogenesis of atherosclerosis through its anti-inflammatory and antioxidant properties, we tested whether the expression of six single nucleotide polymorphisms (SNPs) of the melatonin receptor differs in acute myocardial infarction (AMI) patients with acute myocardial infarction (n = 300) compared with healthy age- and sex-matched controls (n = 250). Finally, only MEL1A receptor SNP rs28383653 was selected because of Hardy-Weinberg equilibrium (χ(2) = 0.49). The distribution of genotype frequencies for this SNP showed that the unfavourable CT genotype was significantly more frequent in patients with AMI than in controls (4.5% versus 1.3%; P = 0.006). Multivariable analysis showed a significantly higher frequency of the unfavourable CT genotype in AMI patients with peripheral arteriopathy (28% versus 10%; P = 0.01). This finding suggests a synergism effect between the unfavourable genotype (CT) of the MELIA receptor SNP and the vascular disease in this subgroup of patients. To our knowledge, this is the first study to report an association between a genetic polymorphism of the melatonin receptor 1A and CAD.

Role of myeloperoxidase as predictor of systemic inflammatory response syndrome in patients with ST-segment elevation myocardial infarction after primary percutaneous coronary intervention.

Elevated cytokine levels have been reported after ischemia/reperfusion injury and might cause a systemic inflammatory response syndrome (SIRS) after primary percutaneous coronary intervention (PPCI). High myeloperoxidase (MPO) levels are reported to be a risk factor for early cardiac events in patients with acute coronary syndrome. Its role as a predictor of SIRS in patients with ST-segment elevation myocardial infarction treated with PPCI is unclear. Therefore, the aim of the present study was to investigate the role of MPO as a predictor of SIRS in patients with ST-segment elevation myocardial infarction treated with PPCI. A total of 250 patients with ST-segment elevation myocardial infarction treated with PPCI were admitted to our coronary care unit. The serum MPO levels were measured at admission using a commercially available enzyme-linked immunosorbent assay. Of the 250 patients, 47 developed SIRS within 48 hours after their admission to the coronary care unit; 10 of these patients were excluded from analysis because of the suspicion of sepsis. The remaining 203 patients had no SIRS during their coronary care unit stay. Compared to patients without SIRS, those with SIRS had greater serum MPO values (81.35 +/- 18.07 vs 67.03 +/- 16.98 ng/ml, p <0.0001) after PPCI. After controlling for different baseline clinical, laboratory, and angiographic variables, the baseline serum MPO levels were an independent predictor of SIRS (odds ratio 4.2, 95% confidence interval 1.9 to 8.4, p <0.001). In conclusion, our results have demonstrated that MPO is an independent predictor of SIRS after PPCI, suggesting a new clue for the interpretation of this phenomenon.

Intracoronary versus intravenous abciximab administration in patients with ST-elevation myocardial infarction undergoing thrombus aspiration during primary percutaneous coronary intervention--effects on soluble CD40 ligand concentrations.

INTRODUCTION: CD40 ligand has been suggested to play a pathogenic role in atherogenesis and coronary artery disease progression. Clinical studies suggest that intravenous (IV) abciximab administration attenuates the acute inflammatory response associated with percutaneous coronary intervention (PCI). The anti-inflammatory effects of intracoronary (IC) versus IV administration of abciximab have not been systematically investigated. We assessed changes in soluble CD40 ligand (sCD40L) concentrations in response to IC versus IV abciximab in patients with ST-elevation myocardial infarction (STEMI) undergoing thrombus-aspirating device during primary PCI. METHODS: Patients were randomized to receive IC (n=25) or IV (n=25) bolus abciximab followed in every case by a 12-h IV abciximab infusion. sCD40L was measured immediately before the administration of abciximab (baseline) and 60min post bolus administration. RESULTS: Clinical baseline and angiographic characteristics were similar in both patient groups. Similarly, there were no significant differences in baseline serum sCD40L levels in the IC group compared to IV group (116.6+/-42.13pg/mL vs 124.9+/-43.04pg/mL, P=0.49). At 60min post PCI, however, sCD40L levels decreased by 23% (P<0.001) in the IC group and by 11% (P<0.001) in the IV group. sCD40L levels 60min post PCI were significantly reduced, particularly in the IC group compared to the IV group (73.04+/-12.21pg/mL vs 99.92+/-25.89pg/mL, P<0.001). CONCLUSION: In STEMI patients undergoing primary PCI, IC bolus administration of abciximab was associated with a larger reduction in sCD40L levels compared to standard IV bolus. Whether this more powerful anti-inflammatory effect of IC abciximab translates into improved clinical outcomes deserves investigation.

Does ischemia-modified albumin add prognostic value to the Thrombolysis In Myocardial Infarction risk score in patients with ST-segment elevation myocardial infarction treated with primary angioplasty?

BACKGROUND: The aim of the present study was to evaluate whether or not an elevated ischaemia-modified albumin (IMA) level provides any additional prognostic information to the validated Thrombolysis In Myocardial Infarction (TIMI) risk score in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI). METHODS: One hundred seven consecutive STEMI patients treated with primary PCI were included. The incidence of 30-day death was the prespecified primary end point. Serum IMA was measured immediately at hospital arrival. RESULTS: The incidence of the primary end point was 6.5%. A significant predictive value of IMA in relation to the primary end point was indicated by an area under the ROC curve of 0.71 (p = 0.01). In the multivariate analysis, increased IMA remained a significant predictor of the primary end point after adjustment for TIMI risk predictors (p = 0.019). The area under the ROC curve for the TIMI risk score was 0.68 (p = 0.03). The addition of IMA to the TIMI risk score did not improve its prognostic value (area under the ROC curve 0.60, p = 0.25). CONCLUSION: IMA levels obtained at admission are a powerful indicator of short-term mortality in STEMI patients treated with primary PCI, but do not seem to be a marker that adds prognostic information to the validated STEMI TIMI risk score.

Role of ischemia modified albumin to ST-segment resolution after mechanical reperfusion in patients with ST-segment elevation myocardial infarction.

OBJECTIVE: To investigate the possible association between admission ischemia modified albumin (IMA) levels and ST-segment resolution (STR) in ST-segment elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PCI). MATERIALS AND METHODS: We studied 117 patients with a first STEMI within 6h of the onset of pain. Admission serum IMA concentration was measured using a validated assay. The worst single electrocardiogram lead before and 90min after primary PCI was analyzed, and patients were divided into two groups according to the degree of STR: complete (> or =70%) or incomplete (<70%). RESULTS: Of the 117 patients, 70 (60%) had complete STR, and 47 (40%) incomplete STR. Serum IMA concentrations were significantly higher in patients that had incomplete STR (0.383+/-0.060A.U. vs. 0.297+/-0.056A.U., p<0.001). IMA levels >0.325A.U. demonstrated a sensitivity of 91.4% and a specificity of 45.7% for the diagnosis of incomplete STR; the area under the receiver operator characteristic curve was 0.849 (95% CI 0.77-0.92, p=0.0001). Moreover, IMA values were an independent predictor of incomplete STR even after adjustment for potential confounders (OR 2.34; 95% CI 1.20-4.64, p=0.01). CONCLUSIONS: IMA may be a useful biomarker for the identification of incomplete STR in STEMI patients presenting to hospital within 6h of the onset of pain.

Prognostic value of admission myeloperoxidase levels in patients with ST-segment elevation myocardial infarction and cardiogenic shock.

Inflammation plays a critical role in acute myocardial infarction. One inflammatory marker is myeloperoxidase (MPO). Its role as a predictor of in-hospital death in patients with ST-segment elevation myocardial infarction (STEMI) presenting with cardiogenic shock (CS) is unclear. Therefore, the aim of this study was to investigate the role of MPO as a predictor of in-hospital death in patients with STEMIs presenting with CS and treated with primary percutaneous coronary intervention. In 38 consecutive patients with CS complicating STEMIs who were treated with primary percutaneous coronary intervention, serum MPO levels were measured at coronary care unit admission using a commercially available enzyme-linked immunosorbent assay. The primary study end point was in-hospital cardiac death. Among the 38 patients included in the study, 20 died during their coronary care unit stays, whereas 18 survived. Compared with patients who survived, patients who died showed, at coronary care unit admission, higher serum MPO levels (81 +/- 28 vs 56 +/- 23 ng/ml, p <0.006). After controlling for different baseline clinical, laboratory, and angiographic variables, baseline serum MPO level was an independent predictor of in-hospital mortality on multivariate analysis (odds ratio 3.9, 95% confidence interval 1.8 to 7.5, p <0.001). In conclusion, admission MPO concentration is an independent predictor of in-hospital mortality in patients with STEMIs presenting with CS.

Light/dark patterns of soluble vascular cell adhesion molecule-1 in relation to melatonin in patients with ST-segment elevation myocardial infarction.

Elevated levels of soluble cellular adhesion molecules have been reported in patients with acute coronary syndromes. Likewise, a relation between decreased nocturnal melatonin levels and coronary artery disease has been suggested. The aim of the present study was to investigate the day-night variations in the concentration of soluble vascular cell adhesion molecule-1 (sVCAM-1) in patients with ST-segment elevation myocardial infarction (STEMI) in relation to the light/dark melatonin pattern. Ninety consecutive patients with STEMI who were admitted to the Coronary Care Unit of our institution were studied. We also recruited 70 age- and gender-matched healthy normal subjects. Blood samples were drawn at 09:00 and 02:00 hr, while patients were at rest, for the assessment of sVCAM-1 and melatonin, which were measured using commercially available ELISA. In STEMI patients, melatonin concentrations maintained a diurnal variation, but the difference between nocturnal and diurnal levels was less than that in healthy subjects (P < 0.0001). In contrast to findings with melatonin, sVCAM-1 levels showed no diurnal variations in control subjects. In the STEMI group, however, sVCAM-1 concentration at 02:00 hr was significantly higher than that during the light phase (09:00 hr; 1391 +/- 38 versus 1200 +/- 43 ng/mL, P < 0.05). The results suggest that diurnal variations in endogenous sVCAM-1 production in STEMI patients might be related to an attenuated circadian secretion of melatonin.

Effects of levosimendan versus dobutamine on long-term survival of patients with cardiogenic shock after primary coronary angioplasty.

BACKGROUND: Cardiogenic shock (CS) after ST elevation myocardial infarction (STEMI) worsens patient's outcome. Levosimendan treatment offers short-term survival benefit in acute heart failure but its effect on long-term outcome remains unclear. We sought to assess the effect on long-term survival of levosimendan compared to dobutamine treatment in patients with STEMI revascularized by primary coronary angioplasty (PCI) who subsequently developed CS. METHODS AND RESULTS: Twenty-two consecutive STEMI patients with CS after PCI randomized to receive levosimendan or dobutamine treatment for 24 h were followed-up for twelve months. Complete follow-up was obtained in 100% of them. The endpoint was cardiac death. Baseline clinical and haemodynamic characteristics were similar in both groups. The probability of survival calculated with Kaplan-Meier curves analysis showed no statistically significant differences between both groups (p=0.24). CONCLUSIONS: Levosimendan compared to dobutamine did not improve long-term survival in STEMI patients revascularized by PCI who developed CS.

Effects of levosimendan versus dobutamine on left ventricular diastolic function in patients with cardiogenic shock after primary angioplasty.

BACKGROUND: Levosimendan is a new calcium sensitizer with positive inotropic properties. In previous studies, it has recently been shown that levosimendan improves the Doppler echocardiographic parameters of the left ventricular (LV) diastolic function in patients with anterior acute myocardial infarction. We sought to evaluate the effects of levosimendan compared to dobutamine on LV diastolic function, using conventional transmitral Doppler, in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) who subsequently developed cardiogenic shock. METHODS: We randomized 22 consecutive STEMI patients with cardiogenic shock after primary PCI to levosimendan or dobutamine infusion and we also analyzed the diastolic function using conventional transmitral Doppler flow. RESULTS: Twenty-four hours after the initiation of the drug infusion, patients treated with levosimendan (n=11) showed a significant reduction of the isovolumetric relaxation time (116+/-15.2-70.4+/-10.8 ms; P<.001), and a significant increase of the E/A ratio (0.6+/-0.3-1.4+/-0.5; P<.001). In the dobutamine group (n=11), no statistically significant differences were noted in the echocardiographic Doppler indexes. CONCLUSION: Levosimendan seems to be effective in improving the Doppler echocardiographic parameters of LV diastolic function in patients with STEMI revascularised by primary PCI who developed cardiogenic shock.

Association of ischemia-modified albumin and melatonin in patients with ST-elevation myocardial infarction.

INTRODUCTION: It has been proposed that reactive oxygen species (ROS) generated during myocardial ischemia-reperfusion modify the N-terminus of serum albumin resulting in ischemia-modified albumin (IMA) formation. Likewise, several recent publications provide evidence that melatonin, a circadian endogenously produced indolamine, is a direct scavenger of ROS. We sought to investigate the relationship between IMA and melatonin in ST- elevation myocardial infarction (STEMI). METHODS: We compared IMA and melatonin levels in 27 patients with STEMI undergoing primary angioplasty and 20 age- and gender-matched healthy normal subjects. Blood samples were drawn at 02:00h (night period) and 09:00h (day period) while patients were resting, to assess IMA and melatonin. RESULTS: In both groups, melatonin concentrations maintained a diurnal variation, but the difference between nocturnal and diurnal levels was less in the STEMI-patients than in the control group (p<0.001). In contrast to findings about melatonin, IMA levels showed no diurnal variations in control subjects. However, the STEMI group showed a diurnal fluctuation with significantly higher levels at 02:00h (p<0.01). The association between IMA and melatonin remained statistically significant after adjustment for cardiovascular risk factors. An inverse correlation between IMA and melatonin at 02:00h and at 09:00h was observed, with respective r-values of -0.42 (p<0.03) and -0.57 (p<0.002). CONCLUSIONS: Circulating IMA is negatively correlated to melatonin in STEMI-patients. Our results suggest that melatonin might exert a beneficial effect as a radical scavenger in a human model of myocardial ischemia-reperfusion.

Relation of ischemia-modified albumin levels and left ventricular systolic function in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention.

BACKGROUND: Ischemia-modified albumin (IMA) has been shown to be elevated in patients after percutaneous coronary intervention (PCI). Our goal was to investigate the association between IMA levels and left ventricular ejection fraction in patients with ST-segment elevation myocardial infarction (STEMI) treated with PCI and who developed heart failure during their Coronary Care Unit (CCU) stay. METHODS: We assessed 75 patients with a first STEMI. Presence of heart failure was assessed during CCU admission, and patients were subdivided into 2 groups: group A (n=45) comprised patients in Killip class I, and group B (n=30) Killip classes>I. Serum IMA concentration was measured within the first 15 min post-PCI. The IMA measured was performed using an indirect method based in the Albumin Cobalt Binding (ACB) colorimetric assay. The ideal cutoff value of IMA was calculated by the receiver operating characteristic (ROC) curve analysis. RESULTS: Serum IMA concentrations were significantly higher in group B than in group A (0.37+/-0.09 vs 0.30+/-0.06 (A.U.); p<0.0001). The sensitivity and specificity of IMA for heart failure were 93.3% and 37.7%, respectively, at 0.31 A.U. Multivariable adjustment IMA showed a significant inverse correlation with left ventricular ejection function (r=-0.32; p=0.004). On multivariable analysis both IMA (OR=2.1, 95%CI: 1.2 to 3.9, p<0.001) and left ventricular ejection function (OR=1.7, 95%CI: 1.1 to 2.1, p<0.01) correlated with the occurrence of heart failure. CONCLUSION: In patients with STEMI undergoing PCI, serum IMA concentrations are significantly related to LVEF and represent an early marker of left ventricular dysfunction.

Vocal cord haematoma after tenecteplase thrombolysis.

At present, thrombolysis remains the principal reperfusion strategy for ST-elevation acute coronary syndromes in most countries, due to the limited availability of primary angioplasty. Haemorrhagic complications, which are among the most frequent side effects, are usually not very important. As a matter of fact, 70% of the bleeding takes place at venepuncture sites and does not require special treatment. We report an unusual case of vocal cord haematoma after thrombolysis with tenecteplase in a patient with acute myocardial infarction. As far as we know, this type of side effect has only been described once in the literature, namely, after thrombolysis with tissue plasminogen activator in deep vein thrombosis.