Low serum albumin levels and in-hospital outcomes in patients with ST segment elevation myocardial infarction.

BACKGROUND AND AIMS: Low serum albumin (SA) is associated with an increased risk of long-term adverse events (AEs) among patients with chronic coronary syndromes. Its prognostic role in patients with ST-elevation myocardial infarction (STEMI) is less clear. To investigate the association between low SA and in-hospital AEs in STEMI patients. METHODS AND RESULTS: Multicenter retrospective cohort study of 220 STEMI patients undergoing primary percutaneous coronary intervention within 12 h from the onset of symptoms. Hypoalbuminemia was defined by serum SA <35 g/L. SA. In-hospital AEs were defined as cardiogenic shock, resuscitated cardiac arrest and death. Median SA was 38 (IQR 35.4-41.0) g/L and 37 (16.8%) patients showed hypoalbuminemia (<35 g/L) on admission. Patients with hypoalbuminemia were older, more frequently women and diabetics, prior CAD and HF. Furthermore, they showed lower hemoglobin levels and impaired renal function. At multivariable logistic regression analysis, diabetes (odds ratio [OR]:4.59, 95% confidence interval [CI] 1.71-12.28, p = 0.002) and haemoglobin (OR:0.52, 95%CI 0.37-0.72, p < 0.001) were associated with low SA. In a subgroup of 132 patients, SA inversely correlated with D-Dimer (rS -0.308, p < 0.001). Globally, twenty-eight (14.6%) AEs were recorded. Hypoalbuminemia (OR:3.43, 95%CI 1.30-9.07, p = 0.013), high-sensitive (HS)-Troponin peak above median (OR:5.41, 95%CI 1.99-14.7, p = 0.001), C-reactive protein (CRP) peak above median (OR:6.03, 95%CI 2.02-18.00, p = 0.001), and in-hospital infection (OR:3.61, 95%CI 1.21-10.80, p = 0.022) were associated with AEs. CONCLUSION: Low SA levels are associated with worse in-hospital AEs in STEMI patients, irrespective of HS-troponin and CRP plasma levels. Our findings suggest that low SA may contribute to the pro-thrombotic phenotype of these patients.

Long-term outcome of patients with ST-segment elevation myocardial infarction treated with low-dose intracoronary thrombolysis during primary percutaneous coronary intervention: the 5-year results of the DISSOLUTION Trial.

We tested the hypothesis that adjunctive thrombolysis at time of primary percutaneous coronary intervention (PCI) may affect favourably the long-term outcome of patients with ST elevation myocardial infarction (STEMI). To this end, we undertook a substudy of the DISSOLUTION (Delivery of thrombolytIcs before thrombectomy in patientS with ST-segment elevatiOn myocardiaL infarction Undergoing primary percuTaneous coronary interventION) trial. A total of 95 patients were randomized to local delivery of urokinase (n = 48) or placebo (n = 47). After PCI, a greater proportion of patients receiving urokinase had an improvement in myocardial perfusion, as indicated by a significantly higher final Thrombolysis in myocardial infarction (TIMI) grade 3, myocardial blush grade, and 60-min ST-segment resolution > 70%, as well as lower corrected TIMI frame count. At 1-year echocardiography, urokinase-treated patients exhibited significantly lower LV dimension, as well as higher LV ejection fraction and wall motion score index as compared with placebo-treated patients. At 5 years, major acute cardiovascular events (MACEs) were significantly less common in the urokinase group (P = 0.023), mainly due to a lower occurrence of hospitalisation for heart failure (P = 0.038). Multivariate analysis showed that factors independently associated with 5-year occurrence of MACEs were LV remodelling at 1-year echocardiography (P = 0.0001), 1-year LV ejection fraction (P = 0.0001), TIMI grade flow 0-2 (P = 0.0019), and age at time of PCI (P = 0.0173). In conclusion, low-dose intracoronary urokinase during primary PCI is associated with a more favourable 5-year outcome of patients with STEMI.

Usefulness of intracardiac echocardiography with a mechanical probe for catheter-based interventions: a 10-year prospective registry.

BACKGROUND: The clinical outcome benefit of intracardiac echocardiography (ICE) with a mechanical probe during congenital heart disease interventions has not been fully investigated. We reported the long-term results of a prospective registry of interatrial shunt closure guided by mechanical ICE. METHODS: We enrolled 537 patients (mean age 48 ± 19.0 years, 378 females) submitted to ICE-aided procedures in a prospective registry over a 10-year period (September 2003-September 2013). All patients underwent transesophageal echocardiography (TEE) before the planned procedure. We evaluated (1) structure identification capability, (2) fossa ovale and interatrial septum component measurement, (3) procedure monitoring capability, (4) procedural and fluoroscopy times, and radiograph dose, (5) probe-related complications. RESULTS: ICE was successfully performed and was able to correctly identify the structures previously assessed by TEE in all patients. In 24 patients (4.5%), ICE allowed better anatomy definition than TEE. In 35 other patients (6.5%), ICE identified structures not observed by TEE, which led to change indications to interventions or the operative technique to be used. In 131 patients (24.4%), ICE evaluation led to change the planned device to be implanted. There was only one probe-related complication (0.2%). CONCLUSIONS: Mechanical ICE may offer a valid alternative to conventional TEE in guiding congenital heart disease interventional procedures.

Immediate results of bifurcational stenting assessed with optical coherence tomography.

BACKGROUND: A tubular stent may adapt with difficulty to coronary bifurcation lesions (CBLs). METHODS: Time domain or frequency domain (FD) optical coherence tomography (OCT) was performed to assess strut apposition immediately after stent implantation across four segments inside the bifurcation, in a consecutive series of patients. OCT pullbacks were performed in the main vessel (MV). RESULTS: A total of 13,142 struts in 45 CBL in 41 patients were assessed. Strut malapposition was significantly more frequent in the half bifurcation facing the side-branch (SB) ostium (42.9%) than in the proximal segment of the bifurcation 11.8%, half bifurcation opposite the SB 6.7%, or the distal segment 5.7% (all P < 0.0001). Lesions (n = 15) treated with stenting of both MV and SB had a total higher rate of malapposition than those (n = 30) treated with stenting of the MV only (17.6% vs. 9.5%; P = 0.0014). In latter group, lesions treated with FD-OCT-guided stent implantation (n = 13) presented a lower rate of malapposition than those treated with conventional angiographic-guided stent implantation (n = 17) (7.1% vs. 17.5%; P = 0.005). CONCLUSIONS: In CBL, strut malapposition is particularly high at the SB ostium. However, a strategy of stenting MV only with adjunctive FD-OCT guidance is associated with lower rates of malapposition.

Comprehensive echocardiographic assessment of right ventricular function, pulmonary arterial elastic properties and ventricular-vascular coupling in adult patients with repaired tetralogy of fallot: clinical significance of 3D derived indices.

We aimed to comprehensively analyze by three-dimensional speckle-tracking echocardiography (3DSTE) and Doppler echocardiography right ventricular (RV) performance, pulmonary arterial (PA) elastic properties and right ventricular-pulmonary artery coupling (RVPAC) in patients with repaired tetralogy of Fallot (rTOF) and assess the feasibility and clinical utility of related echocardiographic indices. Twenty-four adult patients with rTOF and twenty-four controls were studied. RV end-diastolic volume(3D-RVEDV), RV end-systolic volume(3D-RVESV), RV ejection fraction(3D-RVEF), RV longitudinal strain(3D-RVLS) and RV area strain(3D-RVAS) were calculated by 3DSTE. RV end-systolic area (RVESA) was obtained by planimetry. Pulmonary regurgitation (PR) was assessed as trivial/mild or significant by cardiac magnetic resonance (CMR) and color-Doppler. Pulmonary artery (PA) elastic properties were determined using two-dimensional/Doppler echocardiography. RV systolic pressure (RVSP) was measured using standard Doppler methods. RVPAC was assessed using various 3DSTE-derived parameters (3DRVAS/RVSP, 3DRVLS/RVESA, 3DRVAS/RVESV). Overall, 3DRVEF and 3DRVAS were impaired in rTOF patients compared with controls. PA pulsatility and capacitance were reduced (p = 0.003) and PA elastance was higher (p = 0.0007) compared to controls. PA elastance had a positive correlation with 3DRVEDV (r = 0.64, p = 0.002) and 3DRVAS (r = 0.51, p = 0.02). By ROC (receiver operating characteristics) analysis, 3DRVAS/RVESV, 3DRVAS/RVSP and 3DRVLS/RVESA cutoff values of 0.31%/mmHg, 0.57%/mmHg and 0.86%/mmHg, respectively, had 91%, 88% and 88% sensitivity and 81%, 81% and 79% specificity in identifying exercise capacity impairment. In rTOF patients increased 3DSTE-derived RV volumes and impaired RV ejection fraction and strain are associated with reduced PA pulsatility and capacitance and increased PA elastance. 3DSTE-derived RVPAC parameters using different afterload-markers are accurate indices of exercise capacity.

A machine-learning based bio-psycho-social model for the prediction of non-obstructive and obstructive coronary artery disease.

BACKGROUND: Mechanisms of myocardial ischemia in obstructive and non-obstructive coronary artery disease (CAD), and the interplay between clinical, functional, biological and psycho-social features, are still far to be fully elucidated. OBJECTIVES: To develop a machine-learning (ML) model for the supervised prediction of obstructive versus non-obstructive CAD. METHODS: From the EVA study, we analysed adults hospitalized for IHD undergoing conventional coronary angiography (CCA). Non-obstructive CAD was defined by a stenosis < 50% in one or more vessels. Baseline clinical and psycho-socio-cultural characteristics were used for computing a Rockwood and Mitnitski frailty index, and a gender score according to GENESIS-PRAXY methodology. Serum concentration of inflammatory cytokines was measured with a multiplex flow cytometry assay. Through an XGBoost classifier combined with an explainable artificial intelligence tool (SHAP), we identified the most influential features in discriminating obstructive versus non-obstructive CAD. RESULTS: Among the overall EVA cohort (n = 509), 311 individuals (mean age 67 ± 11 years, 38% females; 67% obstructive CAD) with complete data were analysed. The ML-based model (83% accuracy and 87% precision) showed that while obstructive CAD was associated with higher frailty index, older age and a cytokine signature characterized by IL-1ß, IL-12p70 and IL-33, non-obstructive CAD was associated with a higher gender score (i.e., social characteristics traditionally ascribed to women) and with a cytokine signature characterized by IL-18, IL-8, IL-23. CONCLUSIONS: Integrating clinical, biological, and psycho-social features, we have optimized a sex- and gender-unbiased model that discriminates obstructive and non-obstructive CAD. Further mechanistic studies will shed light on the biological plausibility of these associations. CLINICAL TRIAL REGISTRATION: NCT02737982.

Early beneficial effects of drug-eluting stents in vein grafts wane during long term follow-up: a case-control study.

OBJECTIVES: The aim of the study was to compare outcomes of drug-eluting stents (DES) versus bare-metal stents (BMS) in saphenous vein graft (SVG) interventions in a case-control study with a long-term follow-up. BACKGROUND: Safety and efficacy of DES in SVG interventions are still controversial. METHODS: We performed a multicenter registry assessing clinical outcomes with DES vs. BMS. We included 311 patients (239 men, age 68 ± 8 years) who underwent percutaneous coronary interventions (PCI) of SVG lesions with DES (n = 138) or BMS (n = 173) with a 2-year follow-up. RESULTS: The two groups were similar for age, sex, main risk factors, incidence of diabetes, use of IIb/IIIa antagonists, use of aspiration devices or filters, number of stents, and total stent length. Overall, at 9 months follow-up incidence of major adverse cardiac events (MACE) and target vessel revascularization (TVR) were significantly lower in the DES group compared with the BMS group (10.9% vs. 22.0%, P = 0.014 and 8.7% vs. 19.1% in DES and BMS respectively, P = 0.015), while there was no significant difference in incidence of myocardial infarction (5.1% vs. 5.2%, P = 0.96) or death (2.2% vs. 4%, respectively, P = 0.54). However, at 24-month follow-up incidence of MACE was 29.7% in the DES group and 37.0% in BMS group (P = 0.29); incidence of TVR (23.2% vs. 28.9% P = 0.39), myocardial infarction (9.4% vs. 9.2%), death (7.2% vs. 6.9%) were also similar in the two groups. CONCLUSIONS: Although DES appear safe, our findings suggest that the early benefit of DES in SVG may rapidly wane during long-term follow-up.

Unraveling Pathophysiology of Takotsubo Syndrome: The Emerging Role of the Oxidative Stress's Systemic Status.

Takotsubo Syndrome (TTS) is usually triggered by emotional or physical stressors, thus suggesting that an increased sympathetic activity, leading to myocardial perfusion abnormalities and ventricular dysfunction, plays a major pathogenetic role. However, it remains to be elucidated why severe emotional and physical stress might trigger TTS in certain individuals but not others. Clinical research has been focused mainly on mechanisms underlying the activation of the sympathetic nervous system and the occurrence of myocardial ischemia in TTS. However, scientific evidence shows that additional factors might play a pathophysiologic role in the condition's occurrence. In this regard, a significant contribution arrived from metabolomics studies that followed the systemic response to TTS. Specifically, preliminary data clearly show that there is an interplay between inflammation, genetics, and oxidative status which might explain susceptibility to the condition. This review aims to sum up the established pathogenetic factors underlying TTS and to appraise emerging mechanisms, with particular emphasis on oxidative status, which might better explain susceptibility to the condition.

Endothelial Progenitor Cells in Coronary Artery Disease: From Bench to Bedside.

Endothelial progenitor cells (EPCs) are a heterogeneous group of cells present in peripheral blood at various stages of endothelial differentiation. EPCs have been extensively investigated in patients with coronary artery disease (CAD), with controversial findings both on their role in atherosclerosis progression and in the process of neointimal growth after a percutaneous coronary intervention (PCI). Despite nearly 2 decades of experimental and clinical investigations, however, the significance of EPCs in clinical practice remains unclear and poorly understood. This review provides an update on the role of EPCs in the most common clinical scenarios that are experienced by cardiologists managing patients with CAD. We here summarize the main findings on the association of EPCs with cardiovascular risk factors, coronary atherosclerosis, and myocardial ischemia. We then discuss the potential effects of EPCs in post-PCI in-stent restenosis, as well as most recent findings with EPC-coated stents. Based on the mounting evidence of the relationship between levels of EPCs and several different adverse cardiovascular events, EPCs are emerging as novel predictive biomarkers of long-term outcomes in patients with CAD.

Toll-like receptor 4 activation in platelets from myocardial infarction patients.

INTRODUCTION: Platelet toll-like receptor 4 (TLR4) is overexpressed in patients with myocardial infarction (MI) but it remains to elucidate if it is activated and the potential trigger. METHODS: Serum levels of lipopolysaccharides (LPS) and platelet aggregation (PA) by collagen alone or in combination with a TLR4 inhibitor (TLR4i) were studied ex vivo in platelets from 40 MI patients and 40 controls matched for age, sex and atherosclerotic risk factors; platelet TIR domain-containing adaptor protein (TIRAP) and TIRAP-MyD88 interaction were also investigated by western blot and co-immunoprecipitation, respectively. In vitro experiments were conducted to see if LPS triggers platelet TIRAP phosphorylation. RESULTS: Serum LPS was significantly higher in patients compared to controls (29.5±7.1 vs 16.2±3.8 pg/mL; p<0.001). Collagen-stimulated platelets from MI pre-treated with TLR4i showed a significant decrease of PA compared to platelets stimulated with collagen. Ex vivo study showed that TIRAP phosphorylation as well as TIRAP-MyD88 co-immunoprecipitation were higher in patients compared to controls. In vitro study showed that LPS, at concentrations like those found in MI, dose-dependently activated TIRAP and amplified the platelet response to the agonist, an effect blunted by TLR4i. CONCLUSION: The study provides evidence that in MI patients platelet TLR4 is activated and suggests circulating LPS as potential trigger.

A Pilot Study on the 1H-NMR Serum Metabolic Profile of Takotsubo Patients Reveals Systemic Response to Oxidative Stress.

Takotsubo syndrome (TTS) presents as an acute coronary syndrome characterized by severe left ventricular (LV) dysfunction and non-obstructive coronary artery disease that typically shows spontaneous recovery within days or weeks. The mechanisms behind TTS are mainly related to beta-adrenergic overstimulation and acute endogenous catecholamine surge, both of which could increase oxidative status that may induce further deterioration of cardiac function. Although several studies reported evidence of inflammation and oxidative stress overload in myocardial tissue of TTS models, systemic biochemical evidence of augmented oxidant activity in patients with TTS is lacking. In this study, serum samples of ten TTS patients and ten controls have been analyzed using 1H-NMR spectroscopy. The results of this pilot study show a marked alteration in the systemic metabolic profile of TTS patients, mainly characterized by significant elevation of ketone bodies, 2-hydroxybutyrate, acetyl-L-carnitine, and glutamate levels, in contrast with a decrease of several amino acid levels. The overall metabolic fingerprint reflects a systemic response to oxidative stress caused by the stressor that triggered the syndrome's onset.

Glutathione Infusion Before and 3 Days After Primary Angioplasty Blunts Ongoing NOX2-Mediated Inflammatory Response.

Background Glutathione is a water-soluble tripeptide with a potent oxidant scavenging activity. We hypothesized that glutathione administration immediately before and after primary angioplasty (primary percutaneous coronary intervention) could be effective in modulating immune cell activation, thereby preventing infarct expansion. Methods and Results One hundred consecutive patients with ST-segment-elevation myocardial infarction, scheduled to undergo primary percutaneous coronary intervention were randomly assigned before the intervention to receive an infusion of glutathione (2500 mg/25 mL over 10 minutes), followed by drug administration at the same doses at 24, 48, and 72 hours elapsing time or placebo. Total leukocytes, NOX2 (nicotinamide adenine dinucleotide phosphate oxidase 2) activation, NO bioavailability, cTpT (serum cardiac troponin T), hsCRP (high-sensitivity C-reactive protein), and TNF-α (tumor necrosis factor α) levels were measured. Left ventricular size and function were assessed within 120 minutes, 5 days, and 6 months from percutaneous coronary intervention. Following reperfusion, a significant reduction of neutrophil to lymphocyte ratio (P<0.0001), hsCRP generation (P<0.0001), NOX2 activation (P<0.0001), TNF-α levels (P<0.001), and cTpT release (P<0.0001) were found in the glutathione group compared with placebo. In treated patients, blunted inflammatory response was linked to better left ventricular size and function at follow-up (r=0.78, P<0.005). Conclusions Early and prolonged glutathione infusion seems able to protect vital myocardial components and endothelial cell function against harmful pro-oxidant and inflammatory environments, thus preventing maladaptive cardiac repair and left ventricular adverse remodeling. Registration URL: https://www.clinicaltrialsregister.eu; Unique identifier: 2014-004486-25.

Partial Sub-Struts Stenting Technique for Emergency Treatment of Very Late LAD Stent Thrombosis: A Case Report.

Although rare, stent thrombosis remains a severe complication after stent implantation owing to its high morbidity and mortality, and represents a challenging scenario for interventional cardiology. Sub-struts stenting could constitute a rare last-resort-bailout technique for recanalization. We present herein a case of acute coronary syndrome secondary to in-stent restenosis and very late thrombosis, successfully treated with a partial sub-struts stenting.

PCSK9 Regulates Nox2-Mediated Platelet Activation via CD36 Receptor in Patients with Atrial Fibrillation.

BACKGROUND: High levels of proprotein convertase subtilisin/kexin 9 (PCSK9) is predictive of cardiovascular events (CVEs) in atrial fibrillation (AF). We hypothesized that PCSK9 may directly induce platelet activation (PA). METHODS: We measured platelet aggregation, recruitment, Thromboxane B2 (TxB2) formation and soluble P-selectin levels as markers of PA and soluble Nox2-derived peptide (sNox2-dp), H2O2, isoprostanes and oxidized Low-Density-Lipoprotein (oxLDL) to analyze oxidative stress (OS) in 88 patients having PCSK9 values < (n = 44) or > (n = 44) 1.2 ng/mL, balanced for age, sex and cardiovascular risk factors. Furthermore, we investigated if normal (n = 5) platelets incubated with PCSK9 (1.0-2.0 ng/mL) alone or with LDL (50 µg/mL) displayed changes of PA, OS and down-stream signaling. RESULTS: PA and OS markers were significantly higher in patients with PCSK9 levels > 1.2 ng/mL compared to those with values < 1.2 ng/mL (p < 0.001). Levels of PCSK9 significantly correlated with markers of PA and OS. Platelets incubation with PCSK9 increased PA, OS and p38, p47 and Phospholipase A2 (PLA2) phosphorylation. These changes were amplified by adding LDL and blunted by CD36 or Nox2 inhibitors. Co-immunoprecipitation analysis revealed an immune complex of PCSK9 with CD36. CONCLUSIONS: We provide the first evidence that PCSK9, at concentration found in the circulation of AF patients, directly interacts with platelets via CD36 receptor and activating Nox2: this effect is amplified in presence of LDL.

Glutathione infusion before primary percutaneous coronary intervention: a randomised controlled pilot study.

OBJECTIVE: In the setting of reperfused ST-elevation myocardial infarction (STEMI), increased production of reactive oxygen species (ROS) contributes to reperfusion injury. Among ROS, hydrogen peroxide (H2O2) showed toxic effects on human cardiomyocytes and may induce microcirculatory impairment. Glutathione (GSH) is a water-soluble tripeptide with a potent oxidant scavenging activity. We hypothesised that the infusion of GSH before acute reoxygenation might counteract the deleterious effects of increased H2O2 generation on myocardium. METHODS: Fifty consecutive patients with STEMI, scheduled to undergo primary angioplasty, were randomly assigned, before intervention, to receive an infusion of GSH (2500 mg/25 mL over 10 min), followed by drug administration at the same doses at 24, 48 and 72 hours elapsing time or placebo. Peripheral blood samples were obtained before and at the end of the procedure, as well as after 5 days. H2O2 production, 8-iso-prostaglandin F2α (PGF2α) formation, H2O2 breakdown activity (HBA) and nitric oxide (NO) bioavailability were determined. Serum cardiactroponin T (cTpT) was measured at admission and up to 5 days. RESULTS: Following acute reperfusion, a significant reduction of H2O2 production (p=0.0015) and 8-iso-PGF2α levels (p=0.0003), as well as a significant increase in HBA (p<0.0001)and NO bioavailability (p=0.035), was found in the GSH group as compared with placebo. In treated patients, attenuated production of H2O2 persisted up to 5 days from the index procedure (p=0.009) and these changes was linked to those of the cTpT levels (r=0.41, p=0.023). CONCLUSION: The prophylactic and prolonged infusion of GSH seems to determine a rapid onset and persistent blunting of H2O2 generation improving myocardial cell survival. Nevertheless, a larger trial, adequately powered for evaluation of clinical endpoints, is ongoing to confirm the current finding. TRIAL REGISTRATION NUMBER: EUDRACT 2014-00448625; Pre-results.

Interplay between Oxidative Stress and Platelet Activation in Coronary Thrombus of STEMI Patients.

BACKGROUND: Platelet activation and oxidative stress seem to play a key role in coronary thrombus formation and are associated with thrombus burden in ST-elevation myocardial infarction (STEMI). However, the interplay between oxidative stress and platelet activation has not been fully elucidated. MATERIALS AND METHODS: For 32 patients with STEMI undergoing primary percutaneous coronary intervention (PPCI) and 10 patients with stable angina (SA) and oxidative stress, as assessed by NADPH isoform 2 activity (soluble Nox2-derived peptide, sNox2-dp), levels of oxidized low-density lipoproteins (oxLDLs) and platelet activation markers such as soluble CD40 Ligand (sCD40L) and soluble P-selectin (sP-selectin) were measured in the retrieved material (coronary thrombi plus blood waste) of STEMI patients and in intracoronary blood of SA patients, respectively, and in peripheral blood samples of both groups. RESULTS: In aspirated thrombi and blood waste of STEMI patients we found higher serum levels of sNox2-dp, oxLDLs, sCD40L, and sP-selectin, as compared to the intracoronary blood samples of SA patients. Moreover, in thrombi and blood waste of STEMI patients, a direct correlation between markers of oxidative stress and of platelet activation was found. Also, in STEMI patients a progressive increase of oxidative stress and platelet activation markers was observed according to the thrombus score burden. STEMI patients showed higher peripheral blood Nox2 activity and oxLDL levels as compared to SA patients. CONCLUSION: This study shows a close relationship between oxidative stress and platelet activation in the intracoronary blood waste and aspirated thrombi of STEMI patients, suggesting a role of oxidative stress in promoting thrombus formation and growth.

Uric acid and contrast-induced nephropathy: an updated review and meta-regression analysis.

INTRODUCTION: Previous studies have suggested a relationship between serum uric acid and contrast-induced nephropathy (CIN). AIM: We performed an updated review and a meta-regression analysis to assess whether serum uric acid is associated with CIN or there exists any relationship between serum uric acid and other risk factors for CIN. MATERIAL AND METHODS: We searched PubMed, Embase and Cochrane databases and reviewed cited references up to July 31, 2018 to identify relevant studies. RESULTS: A total of 6,705 patients from 10 clinical studies were included. CIN occurred in 774 of the 6,705 (12%) patients. Baseline uric acid levels were significantly higher in those who developed CIN (6.51 vs. 5.67 mg/dl; 95% CI: 0.55-1.22, p = 0.00001). Comparison of clinical features showed that patients with CIN were significantly older (69 vs. 63 years; p < 0.00001) and more often had diabetes (42% vs. 32%; p = 0.002) and hypertension (67% vs. 59%; p = 0.03). Also, patients who developed CIN had lower hemoglobin (12.5 vs. 13.6 mg/dl; p < 0.00001) and higher levels of baseline creatinine (1.27 vs. 1.01 mg/dl; p < 0.0001), but had similar levels of glycemia, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride. Also, they showed a lower ejection fraction (45% vs. 50%; p < 0.00001). Meta-regression analysis revealed that uric acid related only to age (r = 0.13, p = 0.03). CONCLUSIONS: Our investigation indicates that uric acid is significantly associated with CIN. Uric acid correlated significantly with age only, and not with other major predictors of CIN. Further studies are therefore needed to verify the potential of uric acid to improve CIN risk stratification.

Bi-Atrial Function before and after Percutaneous Closure of Atrial Septum in Patients with and without Paroxysmal Atrial Fibrillation: A 2-D and 3-D Speckle Tracking Echocardiographic Study.

Our aim was to analyze atrial function with 2-D (2-D-STE) and 3-D (3-D-STE) speckle tracking echocardiography in patients with atrial septal devices and paroxysmal atrial fibrillation (PAF). One hundred sixteen patients and a subgroup of 22 patients who developed PAF after device insertion were studied. Left atrial and right atrial peak longitudinal strain and standard deviations of time to peak strain (TPS) were calculated using 2-D-STE. The left atrial/right atrial emptying fraction and expansion index were determined using 3-D-STE. By multivariate analysis, pre-closure 3-D right atrial expansion index, left atrial time to peak strain, and 3-D left atrial expansion index were independently associated with PAF. Compared with the other indices, receiver operating characteristic analysis revealed better diagnostic accuracy for the combination of pre-closure time to peak strain and 3-D expansion index in detecting PAF. Patients with atrial septal devices have pre-existing left and right atrial dilation and dysfunction as assessed by 2-D-STE and 3-D-STE that appear sensitive for the stratification of PAF risk in this population.

Early metabolic response to acute myocardial ischaemia in patients undergoing elective coronary angioplasty.

Objective: Balloon-induced transient coronary ischaemia represents a model of myocardial ischaemia and reperfusion. We are interested in the very early systemic metabolic response to this event. Methods: Blood samples of patients with stable angina (SA) were collected before and after coronary angioplasty. Serum metabolic profiles were obtained using nuclear magnetic resonance spectroscopy. Univariate and multivariate analyses were used to investigate changes in metabolite concentrations. Results: Thirty-four consecutive patients with SA, undergoing elective coronary angioplasty at Policlinico Umberto I of Rome, were included in this study. Changes in metabolites concentration induced by balloon occlusion in venous and arterial sera were detected. In both serum types, a significant increase in ketone bodies, 2-hydroxybutyrate, glutamine and O-acetylcarnitine concentration is observed, while alanine, lactate, phenylalanine and tyrosine decreased after intervention. Most significant metabolic changes were detected in arterial serum. Conclusions: Our study points out two main global metabolic changes in peripheral blood after balloon-induced coronary ischaemia: ketone bodies increase and lactate decrease. Both could be related to compensation mechanisms finalised to fulfil heart's needs after short period of myocardial ischaemia and probably after reperfusion.