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Background Cardiac resynchronization therapy (CRT) is an effective treatment for left ventricular reverse remodeling (LVRR) in patients with congestive heart failure (HF) and ventricular dyssynchrony. Melatonin is a secretory product of the pineal gland with highly beneficial effects from any tissues including the heart. Herein, we investigated whether the response to CRT is associated with levels of melatonin before CRT implantation in patients with HF and ventricular dyssynchrony. Methods Diurnal melatonin levels were performed in serum from 93 patients with HF and ventricular dyssynchrony before CRT implantation. Moreover, we calculated the MADIT-CRT score. Evaluation of patients at 1-year follow-up included an echocardiographic study since the patients were categorized as responders if they presented both a reduction in left ventricular end-systolic volume index > 10% and an increase in left ventricular ejection fraction > 10%. Results At 1-year, 34 patients (36.5%) were considered responders to CRT according to the predefined criteria. The diurnal melatonin levels were significantly lower in the non-responder group (9.9 ± 2.84 vs 14.7 ± 2.32 pg/mL). After adjustment by multivariate analysis, diurnal serum melatonin levels ( P < 0.001) and diabetes mellitus ( P = 0.03) were predictors of LVRR. On Cox regression analysis, diurnal serum melatonin levels ( P < 0.001) and left atrial volume < 40 mL/m 2 ( P = 0.04) remained independent predictors of the adverse clinical events. The area under of curve for the prediction LVRR of melatonin (0.91, 95%CI 0.85–0.97; P < 0.001) was significantly higher compared to MADIT-CRT score (0.69, 95%CI 0.58–0.80; P = 0.002). Conclusion Diurnal levels of melatonin before CRT implantation are associated with LVRR at 12 month follow-up. [ABSTRACT FROM AUTHOR]

Background: Placental growth factor (PlGF) induces angiogenesis and promotes tissue repair, and plasma PlGF levels change markedly during acute myocardial infarction (AMI). Currently, the impact of obstructive sleep apnea (OSA) in patients with AMI is a subject of debate. Our objective was to evaluate the relationships between PlGF levels and both the severity of acute coronary syndrome (ACS) and short-term outcomes after ACS in patients with and without OSA. Methods: A total of 538 consecutive patients (312 OSA patients and 226 controls) admitted for ACS were included in this study. All patients underwent polygraphy in the first 72 hours after hospital admission. The severity of disease and short-term prognoses were evaluated during the hospitalization period. Plasma PlGF levels were measured using an electrochemiluminescence immunoassay. Results: Patients with OSA were significantly older and more frequently hypertensive and had higher BMIs than those without OSA. After adjusting for age, smoking status, BMI and hypertension, PlGF levels were significantly elevated in patients with OSA compared with patients without OSA (19.9 pg/mL, interquartile range: 16.6–24.5 pg/mL; 18.5 pg/mL, interquartile range: 14.7–22.7 pg/mL; p<0.001), and a higher apnea-hypopnea index (AHI) was associated with higher PlGF concentrations (p<0.003). Patients with higher levels of PlGF had also an increased odds ratio for the presence of 3 or more diseased vessels and for a Killip score>1, even after adjustment. Conclusions: The results of this study show that in patients with ACS, elevated plasma levels of PlGF are associated with the presence of OSA and with adverse outcomes during short-term follow-up. Trial Registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Among the numerous emerging biomarkers, high-sensitivity C-reactive protein (hsCRP) and growth-differentiation factor-15 (GDF-15) have received widespread interest, with their potential role as predictors of cardiovascular risk. The concentrations of inflammatory biomarkers, however, are influenced, among others, by physiological variations, which are the natural, with in individual variation occurring over time. The aims of our study are: (a) to describe the changes in hsCRP and GDF-15 levels over a period of time and after an episode of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and (b) to examine whether the rate of change in hsCRP and GDF-15 after the acute event is associated with long-term major cardiovascular adverse events (MACE). Two hundred and Fifty five NSTE-ACS patients were included in the study. We measured hsCRP and GDF-15 concentrations, at admission and again 36 months after admission (end of the follow-up period). The present study shows that the change of hsCRP levels, measured after 36 months, does not predict MACE in NSTEACS-patients. However, the level of GDF-15 measured, after 36 months, was a stronger predictor of MACE, in comparison to the acute unstable phase. [ABSTRACT FROM AUTHOR]

Platelet aggregates appear to have a pathogenic role in the no-reflow phenomenon, which is associated with impaired clinical outcome in patients with ST-segment elevation myocardial infarction (STEMI). Melatonin, a hormone that plays a major role in biological circadian rhythms, is present in human platelets. Lowered circulating melatonin levels predict poor outcome in patients with STEMI undergoing primary percutaneous coronary intervention (PPCI). We investigated whether intraplatelet melatonin levels correlate with angiographic no-reflow after PPCI in patients with STEMI. We studied 180 consecutive patients with a first STEMI who underwent PPCI within 6 hours from onset of symptoms. Intraplatelet melatonin levels were measured in platelet-rich plasma using an enzymatic immunoassay method. After PPCI, angiographic no-reflow (defined as Thrombolysis In Myocardial Infarction grade <2 flow) was observed in 63 patients (35%). Patients with angiographic no-reflow had lower intraplatelet melatonin levels compared to patients without no-reflow (12.32 ± 3.64 vs 18.62 ± 3.88 ng/100,000 platelets, p <0.0001). After adjusting by potential confounders, binary logistic regression analysis showed that intraplatelet melatonin levels were the only significant predictor of angiographic no-reflow (odds ratio 1.58, 95% confidence interval 1.37 to 1.82, p <0.0001). In conclusion, low intraplatelet melatonin concentration predicts angiographic no-reflow after PPCI in patients with STEMI. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]

Abstract: 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 (≥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. [Copyright &y& Elsevier]

Abstract: Introduction: We sought to investigate whether day-night variations occur in the concentration of circulating soluble CD40 ligand in patients with acute coronary syndrome, as this may have practical implications. Materials and Methods: We assessed 70 consecutive ST-segment elevation myocardial infarction patients admitted into the Coronary Care Unit and 50 control subjects. Each subject was studied under strictly controlled light/dark conditions. Blood samples were drawn at 09:00 h (light phase) and 02:00 h (dark phase). Nocturnal blood samples were drawn by a trained nurse, with the help of a minute torch with a dim red light in order to avoid any direct lighting on the patient during sleep. The soluble CD40 ligand was measured using a commercially available ELISA. Results: Soluble CD40 ligand levels showed no diurnal variations in control subjects. In the ST-segment elevation myocardial infarction group, however, soluble CD40 ligand concentration (pg/mL) in the light phase was significantly higher than that in the dark phase (167.3±63.2 vs 118.9±48.3 pg/mL, p<0.001). Conclusions: The study shows for the first time the existence of diurnal variations in soluble CD40 ligand levels in ST-segment elevation myocardial infarction patients, which indicates the need for standardizing the time of blood sampling for the assessment of this molecule, at least in studies involving ST-segment elevation myocardial infarction patients. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

C-reactive protein, a marker of inflammation, is increasingly measured to stratify risk for coronary artery disease and guide clinical management. Likewise, a relation has been suggested between decreased nocturnal melatonin levels and coronary artery disease. However, little is known about the association between melatonin and C-reactive protein in patients with ischemic heart disease. [Copyright &y& Elsevier]

Background: Diabetic patients are at increased risk for future cardiovascular events after ST-segment elevation myocardial infarction (STEMI). Administration of an intracoronary abciximab bolus during primary percutaneous coronary intervention (PCI) may be beneficial in this high-risk subgroup.Objectives: This study sought to report the 1-year clinical outcomes and cardiac magnetic resonance (CMR) findings in STEMI patients with and without diabetes randomized to intracoronary or intravenous abciximab bolus at the time of primary PCI.Methods: Patient-level data from 3 randomized trials were pooled. The primary endpoint was the composite of death or reinfarction. Comprehensive CMR imaging was performed in 1 study.Results: Of 2,470 patients, 473 (19%) had diabetes and 1,997 (81%) did not. At 1 year, the primary endpoint was significantly reduced in diabetic patients randomized to intracoronary abciximab compared with those randomized to intravenous bolus (9.2% vs. 17.6%; hazard ratio [HR]: 0.49; 95% confidence interval [CI]: 0.28 to 0.83; p = 0.009). The intracoronary abciximab bolus did not reduce the primary endpoint in patients without diabetes (7.4% vs. 7.5%; HR: 0.95; 95% CI: 0.68 to 1.33; p = 0.77), resulting in a significant interaction (p = 0.034). Among diabetic patients, intracoronary versus intravenous abciximab bolus was associated with a significantly reduced risk of death (5.8% vs. 11.2%; HR: 0.51; 95% CI: 0.26 to 0.98; p = 0.043) and definite/probable stent thrombosis (1.3% vs. 4.8%; HR: 0.27; 95% CI: 0.08 to 0.98; p = 0.046). At CMR (n = 792), the myocardial salvage index was significantly increased only in diabetic patients randomized to intracoronary compared with intravenous abciximab (54.4; interquartile range: 35.1 to 78.2 vs. 39.0, interquartile range: 24.7 to 61.7; p = 0.011; p for interaction vs. no diabetes = 0.016).Conclusions: In diabetic patients with STEMI, the administration of intracoronary abciximab improved the effectiveness of primary PCI compared with the intravenous bolus. [ABSTRACT FROM AUTHOR]

Background Although intracoronary abciximab failed to improve prognosis compared with intravenous route in unselected ST-segment elevation myocardial infarction (STEMI) patients, little is known about the role of intracoronary abciximab in diabetic patients. Objectives To evaluate the efficacy of intracoronary abciximab administration in diabetic patients with STEMI undergoing primary percutaneous coronary intervention (PCI). Methods Reperfusional and clinical outcomes of intracoronary abciximab compared with intravenous bolus abciximab according to diabetic status were evaluated in a pooled analysis of five randomized trials including 3158 STEMI patients. The primary clinical endpoint of the study was the composite of death or reinfarction at 30-day follow-up. Results Among 584 diabetic patients (18.5%), the composite of death or reinfarction was significantly reduced with intracoronary abciximab compared to intravenous abciximab (4.7% vs. 8.8%; rate ratio [RR], 0.50; 95% confidence intervals [CI], 0.26–0.99; p = 0.04), driven by numerically lower deaths (3.7% vs. 6.4%; RR, 0.56; 95% CI, 0.26–1.20; p = 0.13). Moreover, a significant reduction in definite or probable stent thrombosis was observed in patients receiving intracoronary abciximab (1% vs. 3.5%; RR, 0.27; 95% CI, 0.07–0.99; p = 0.04). Although formal tests for interaction were not significant, no clinical benefit was apparent in the cohort of STEMI patients without diabetes (n = 2574). Conclusions In diabetic patients with STEMI undergoing primary PCI, intracoronary abciximab may improve clinical outcomes as compared with standard intravenous use. These findings require confirmation in a dedicated randomized trial. [ABSTRACT FROM AUTHOR]