Francesco Saporito

Serum levels of osteoprotegerin and RANKL in patients with ST elevation acute myocardial infarction.

OPG (osteoprotegerin) has been suggested to have an important role in atherogenesis and vascular calcification. In the present study, we have investigated serum OPG and RANKL (receptor activator of nuclear factor kappaB ligand) concentrations in patients with ST elevation AMI (acute myocardial infarction) and established CAD (coronary artery disease). OPG and RANKL were measured in 58 male patients hospitalized in the coronary care unit with ST elevation AMI, in 52 asymptomatic male patients with an established diagnosis of CAD and in 52 healthy male controls. These last two groups were matched with the AMI patients for age and body mass index. OPG was significantly (P<0.05) higher in patients with AMI at 1 h after AMI (8.04+/-4.86 pmol/l) than in both patients with established CAD (4.92+/-1.65 pmol/l) and healthy subjects (3.15+/-1.01 pmol/l). Subjects with established CAD had significantly (P<0.05) increased OPG levels compared with controls. RANKL levels in patients with established CAD (0.02+/-0.05 pmol/l) and with AMI (0.11+/-0.4 pmol/l) were significantly (P<0.05) lower compared with controls (0.32+/-0.35 pmol/l). In the AMI group, OPG decreased significantly (P<0.05) at 1 and 4 weeks after infarction (8.04+/-4.86 compared with 6.38+/-3.87 and 6.55+/-2.6 pmol/l respectively), but OPG levels, either at 1 h or 1-4 weeks after AMI, remained significantly (P<0.05) higher compared with established CAD (4.92+/-1.65 pmol/l) and controls (3.15+/-1.01 pmol/l). Our data show for the first time that OPG levels are increased in ST elevation AMI within 1 h of infarction. Whether the increase in OPG is a consequence or a causal factor of plaque destabilization deserves further investigation.

Age, glomerular filtration rate, ejection fraction, and the AGEF score predict contrast-induced nephropathy in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention.

In patients undergoing primary percutaneous coronary interventions (PCI) for ST‐segment elevation myocardial infarction (STEMI), the occurrence of Contrast‐Induced Nephropathy (CIN) has a pronounced impact both on morbidity and mortality. We investigated the variables associated with CIN development in 481 consecutive patients with STEMI undergoing primary PCI and evaluated the predictive value of a 3‐variable clinical risk score (the AGEF score) based on age, left ventricular ejection fraction (EF), and estimated glomerular filtration rate (eGFR).

Renal Function–Adjusted Contrast Volume Redefines the Baseline Estimation of Contrast-Induced Acute Kidney Injury Risk in Patients Undergoing Primary Percutaneous Coronary Intervention

Background—Age, estimated glomerular renal function (eGFR), and ejection fraction are preprocedural predictors of contrast-induced acute kidney injury (CI-AKI) after primary percutaneous coronary intervention. The effect of renal function–adjusted contrast volume (CV) remains not totally explored, and a threshold has not yet been established. Methods and Results—Logistic regression and receiver-operating characteristic curve analyses were used to assess whether CV/eGFR was an independent predictor of CI-AKI. The increased discriminative value of CV/eGFR over the preprocedural model based on age, eGFR, and ejection fraction was examined using the net reclassification improvement analysis. Of 470 patients enrolled, we observed 25 (5.3%) cases of CI-AKI. Patients with CI-AKI had received a higher renal function–adjusted CV (CV/eGFR 3.62 versus 1.96; P<0.001), and CI-AKI incidence was higher (15%; P<0.001) in patients in the highest quartile of CV/eGFR, corresponding to the cutoff indicated by the receiver-operating characteristic curve (>2.5; area under the curve, 0.77). At multivariable analysis, CV/eGFR above the cutoff (odds ratio, 5.57; P=0.002) remained an independent predictor of CI-AKI. The model with CV/eGFR demonstrated a statistically significantly net reclassification improvement of 0.23 (P=0.021) over the baseline preprocedural model, largely driven by a correct decrease in risk estimates for patients not experiencing CI-AKI, with a likelihood ratio &khgr;2 of 5.973 (P=0.029). Conclusions—CV remains a key risk factor for CI-AKI after primary percutaneous coronary intervention and our study supports the need for minimizing CV, independently from baseline preprocedural risk. A CV restricted to no more than twice and a half the baseline eGFR might be valuable in reducing the risk of CI-AKI.

Crucial role of nuclear factor-κB in neointimal hyperplasia of the mouse carotid artery after interruption of blood flow

We used a molecular genetics approach to investigate the role of nuclear factor-kappaB (NF-kappaB) in neointimal hyperplasia induced by flow interruption of carotid artery in mice. Wild type mice (WT mice) and mice rendered deficient in p105, the precursor of p50, one of the components of the multimeric transcription factor NF-kappaB (NF-kappaB knockout mice; KO mice), were subjected to a complete ligation of the left common carotid artery. Morphometric analysis of the structural alteration caused by the disruption of the arterial blood flow was performed 14 days after surgery. Furthermore the expression of intercellular adhesion molecule-1 (ICAM-1) in injured arteries was evaluated 4 days after artery ligation by the means of reverse transcriptase polymerase chain reaction (RT-PCR) and quantification of the ICAM-1 protein levels. In a separate experiment normal mice were randomly assigned to receive a recombinant adeno-associated virus (rAAV) encoding the gene for the NF-kappaB inhibitory protein IkappaBalpha (rAAV-IkappaBalpha), or the beta-galactosidase gene (rAAV-LacZ), both at a dose of 10(11) copies and 2 weeks later were subjected to the complete ligation of the left carotid artery. NF-kappaB activity (studied by means of electrophoretic mobility shift assay-EMSA), IkappaBalpha expression (evaluated by Western blot analysis) ICAM-1 evaluation (RT-PCR and quantification of the protein levels) and a morphometric analysis were evaluated in the injured arteries. Disruption of the arterial blood flow caused a marked neointimal hyperplasia. The mean intimal area was 0.023+/-0.002 mm(2) in wild type mice compared with 0.002+/-0.001 mm(2) in NF-kappaB knockout mice. ICAM-1 expression was 1.7+/-0.8 relative amount of ICAM-1 mRNA in wild type mice compared with 0.4+/-0.06 relative amount of ICAM-1 mRNA in NF-kappaB knockout mice. ICAM-1 protein levels were also significantly reduced in NF-kappaB knockout mice. Injured arteries treated with rAAV-IkappaBalpha had a greater expression of IkappaBalpha and lower NF-kappaB activity, when compared with vessels treated with rAAV-LacZ. Furthermore, ICAM-1 expression was markedly attenuated by the treatment with rAAV-IkappaBalpha (rAAV-LacZ=1.6+/-0.8 relative amount of ICAM-1 mRNA; rAAV-IkappaBalpha=0.55+/-0.04 relative amount of ICAM-1 mRNA). ICAM-1 protein levels were also significantly decreased in rAAV-IkappaBalpha treated mice. Finally the mean intimal area was 0.028+/-0.003 mm(2) in left carotid arteries treated with rAAV-LacZ whereas it was 0.003+/-0.004 mm(2) in vessels treated with rAAV-IkappaBalpha. Our data indicate that NF-kappaB plays a crucial role in neointimal hyperplasia induced by flow cessation in the mouse carotid artery, and in addition suggest that rAAV-mediated gene transfer of IkappaBalpha might represent a novel therapeutic approach to the treatment of restenosis.

The ACEF score as predictor of acute kidney injury in patients undergoing primary percutaneous coronary intervention

Acute kidney injury (AKI) is an important complication of iodinated contrast media administration [1]. It particularly occurs after coronary procedures; the reported incidencemaybe ashigh as50%, dependingon populations, baseline risk factors and definitions [2]. In patients undergoing primary percutaneous coronary interventions (PCI) for ST-segment elevation myocardial infarction (STEMI), AKI is an established predictor of mortality [3]. Apart from increasing mortality, AKI leads to prolonged hospital stay and additional cost [4] and is also associated with late cardiovascular adverse events [5]. The main purpose of this study was to investigate the risk factors associated with AKI development in patients with STEMI undergoing primary PCI and to evaluate the predictive value of the ACEF score [6]. All the patients consecutively referred to the Coronary Care Unit (CCU) of the University Hospital of Messina from January 2008 to June 2011 for primary PCI in the course of STEMI were included. Primary PCI wasperformed fromthe femoral approach according to standard clinical practice and the indication to intra-aortic balloon pump (IABP) support was left to the discretion of the attending cardiologists. Wall motion abnormalities and left ventricular ejection fraction (EF) were rapidly assessedwith echocardiography in all subjects, either in the Emergency Department or in the pre-cath room. The images were digitally stored and evaluated off-line. Blood samples were collected for measurement of serum creatinine (sCr) on admission, 6 h after the procedure, every day for the following 3 days, and at discharge from the CCU. The ACEF score was calculated according to the original study by Ranucci et al. [6]: age/EF(%) + 1 (if sCr ≥2.0 mg/dL). The primary end point of the study was the occurrence of AKI, defined as an absolute increase in sCr ≥0.5 mg/dL or an increase ≥25% from baseline within 72 h after the administration of contrast medium, without any other plausible etiology. Continuous variables are expressed as mean ± standard deviation and comparedwith t test; categorical variables are expressed as absolute counts and/or percentages and compared by Fisher’s exact test and χ test, as appropriate. Those variables associated with AKI development at univariate analysis were entered into a stepwise forward logistic regression model in order to assess their significance as independent predictors of AKI. The odds ratios (OR) and 95% confidence intervals (CI) are presented. Finally, logistic regression analysis, Hosmer–Lemeshow χ statistic and receiver-operating characteristic (ROC) curve analysis were performed to assess accuracy and calibration of ACEF score as predictor of AKI. A two-tailed p b 0.05 was always requested for statistical significance. The calculations were performed by using Statistical Package for Social Sciences, version 20. Four hundred eighty-one patients with STEMI undergoing primary PCI were enrolled. Demographic characteristics and procedural data are summarized in Table 1. We observed 25 (5.2%) cases of AKI. These patients (Table 1) were older, had a more severe impairment of both basal EF and global hemodynamic status, as expressed by the Killip score, and worse basal sCr thanpatientswithoutAKI. In addition, patientswithAKI had ahigher troponin at admission and a higher prevalence of hypertension and diabetes. From the procedural standpoint (Table 1), patients with AKI had not received a higher total contrast volume nor a higher number of stents. Conversely, they had had a poorer post-procedural TIMI flow (grade 3 in 76% Vs 91.5%, p b 0.001; on average 2.6 ± 0.9 Vs 2.9 ±0.4, p = 0.002) andweremore likely to have received an IABP. They had, on average, a 2-

Systemic embolism in takotsubo syndrome

A 57-year-old woman with acute left leg ischemia due to popliteal artery occlusion and deep T-wave inversion at ECG revealed she had suffered, the day before, from typical chest pain after a confrontational argument; yet, she had not sought medical assistance. Echocardiography showed left ventricular wall motion abnormalities consistent with the diagnosis of emotional stress-induced takotsubo syndrome. Coronary angiography ruled out obstructive atherosclerotic disease and left ventriculography confirmed apical ballooning with evolving thrombosis. Left leg angiography demonstrated diffuse embolisation of the popliteal artery. Ventricular thrombosis is a complication of takotsubo syndrome and has been associated with adverse events supposed to be due to a cardioembolic mechanism, in particular cerebro-vascular accidents. To the best of our knowledge, this is the first direct visualization of systemic cardiogenic embolism in takotsubo syndrome. Physicians should be aware that ventricular thrombosis may be present in the earliest stages of the disease and that emboli dislocation can occur even before wall motion normalization.

Endothelial dysfunction in patients with coronary artery disease: insights from a flow-mediated dilation study.

Background: The use of flow-mediated dilation (FMD) as a surrogate indicator for the extent of coronary artery disease (CAD) remains largely unknown. We assessed FMD at the brachial artery in 89 consecutive patients undergoing coronary angiography. Methods and Results: Patients were classified in groups 0 to 3 according to the number of diseased vessels and the SYNTAX score was calculated. The FMD decreased significantly from groups 0 to 3 (P < .001). There was a significant linear relation between SYNTAX score and FMD (corrected r 2 = .64, P < .001). In multivariate analysis, a reduced FMD was the only significant independent predictor of the presence of CAD (odds ratio [OR] 1.78, P = .032) and of CAD severity (OR 1.85, P = .005). Conclusion: This study confirms that FMD is reduced in patients with CAD and that such reduction in FMD is related to the extent of the disease. Therefore, FMD at the brachial artery is likely to represent a reliable indicator of CAD burden.

Torsades de pointes in congenital long qt syndrome following low‐dose orphenadrine

We report the case of a woman, affected by congenital long QT syndrome (LQTS), who experienced three syncopal episodes shortly after the assumption of a low dose of orphenadrine. The ECG revealed a QT interval of 600 ms, and the corrected QT interval (QTc) was 537 ms. No structural cardiac disease was demonstrated by echocardiography. Orphenadrine treatment was discontinued. During the first 12 h of monitoring, three short‐lasting, asymptomatic episodes of torsades de pointes occurred. No other sustained ventricular arrhythmia was revealed at Holter monitoring in the following days. During the ensuing 6 months, the patient remained asymptomatic, and the QTc did not change. Orphenadrine is an analogue of diphenhydramine, an antihistaminic drug that produces sodium channel blockade similar to that caused by quinidine and other Class Ia antiarrhythmic drugs. Our case rises the suspicion that orphenadrine could cause life‐threatening arrhythmias in LQTS even at a low dose, and independently from concomitant assumption of potentially QT‐prolonging drugs.

Multislice computed tomography demonstration of a coronary-to-pulmonary artery fistula.

MSCT-coronary angiography demonstrated a threevessel CAD; no critical stenosis was apparent, but the images were not conclusive owing to severe vascular calcifications. Moreover, a coronary-to-pulmonary artery fistula was disclosed. The fistula came out (Fig. 1a) frontwards, downwards and rightwards from the proximal segment of the left anterior descending artery (LAD). The fistula then inverted its course and formed two ‘U-shaped’ curves – the former larger and the latter narrower – crossed the LAD itself and reached the left wall of the main pulmonary trunk (Fig. 1b), into which it drained after having become ectasic (Fig. 2).

Percutaneous coronary intervention driven by combined use of intracoronary anatomy and physiology: Towards a tailored therapy for coronary artery disease

Coronary angiography classically allows a bidimensional evaluation of the vascular lumen, however with many limitations in the case of eccentric lesions, irregular contour or tortuosity of the vessel.Moreover, it does not enable to assess neither the features of the vessel wall, nor the functional significance of a lesion [1]. Newer technologies are available to overcome these limitations.We present a case of percutaneous coronary revascularization optimized by combined use of two of the most widely used techniques.