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Background: Residual and significant post-infarction left ventricular (LV) dysfunction, despite technically successful percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI), remains an important clinical issue. In preclinical models low dose insulin-like growth factor 1 (IGF1) has potent cytoprotective and positive cardiac remodelling effects. We studied the safety and efficacy of immediate post PCI low dose intracoronary IGF1 infusion in STEMI patients. Methods: Using a double-blind, placebo controlled, multi-dose study design, we randomized 47 STEMI patients with significantly reduced (≤ 40%) LV ejection fraction (LVEF) after successful PCI to single intracoronary infusion of placebo (n=15), 1.5ng IGF1 (n=16) or 15ng IGF1 (n=16). All received optimal medical therapy. Safety endpoints were freedom from hypoglycaemia, hypotension or significant arrhythmias within 1 hour of therapy. The primary efficacy endpoint was LVEF and secondary endpoints were LV volumes, mass, stroke volume, and infarct size at 2 months follow up, all assessed by MRI. Treatment effects were estimated by analysis of covariance adjusted for baseline (24hrs) outcome. Results: No significant differences in safety endpoints occurred between treatment groups out to 30 days (chi squared test, p-value = 0.77).There were no statistically significant differences in baseline (24 hrs post STEMI) clinical characteristics or LVEF among groups. LVEF at 2 months, compared to baseline, increased in all groups with no statistically significant differences related to treatment assignment. However, compared with placebo or 1.5ng IGF1, treatment with 15ng IGF1 was associated with a significant improvement in indexed LV end-diastolic volume (p=0.018), LV mass (p=0.004) and stroke volume (p=0.016). Late gadolinium enhancement (±SD) at 2 months was lower in 15ng IGF1 (34.5±29.6g) compared to placebo (49.1±19.3g) or 1.5ng IGF1 (47.4±22.4g) treated patients, though the result was not statistically significant (p = 0.095). Conclusion: In this pilot trial, low dose IGF1, given after optimal mechanical reperfusion in STEMI, is safe but does not improve LVEF. However, there is a signal for a dose dependent benefit on post MI remodeling that may warrant further study. Despite timely reperfusion by primary PCI (PPCI) a significant cohort of patients develop adverse left ventricular remodelling with clinical sequelae such as arrhythmia and heart failure[1].Therapeutic approaches to avert such remodeling, including a variety of cell therapy and ischemia- reperfusion-injury mitigation trials have achieved modest success 2.;3. Thus, there remains a significant opportunity for novel therapies in this field.

Increased creatine kinase-MB isoenzymes after coronary stenting are common, and many studies have suggested an association of this increase with an adverse long-term prognosis. How such postprocedural creatine kinase-MB release affects long-term prognosis remains unclear. Whether any actual causal relation exists remains unanswered.

Background— Our group has previously shown that human umbilical vein endothelial cells exposed to smokers’ serum decreased nitric oxide (NO) production and endothelial nitric oxide synthase (eNOS) activity in the presence of increased eNOS expression. In the present study, we examined whether these observations extended to human coronary artery endothelial cells (HCAECs). In addition, the role of reactive oxygen species in the observed alterations was examined. Methods and Results— HCAECs were incubated with serum from 10 nonsmokers and 15 smokers for 12 hours with or without the addition of either polyethylene glycol-superoxide dismutase (PEG-SOD, 300 U/mL), PEG-SOD+PEG-catalase (1000 U/mL), chelerythrine (3 μmol/L), or tetrahydrobiopterin (20 μmol/L). At the end of incubation, NO, eNOS protein, and eNOS activity were measured from the same culture. HCAECs incubated with smokers’ serum alone showed significantly lower NO production ( P P P P P Conclusions— The present study indicates that in vitro, HCAECs show similar changes in NO biosynthesis as human umbilical vein endothelial cells when exposed to smokers’ serum and also confirms that oxidative stress plays a central role in smoking-mediated dysfunction of NO biosynthesis in endothelial cells. Furthermore, these data support other studies suggesting a role for hydrogen peroxide in the upregulation of eNOS.

Objectives The objective of this study was to evaluate the association of high plasma levels of either C-reactive protein (CRP), lipoprotein (a) (Lp[a]) or total homocysteine (tHCY) with the long-term prognosis after successful coronary stenting (CS) Background High plasma levels of either CRP, Lp(a) or tHCY may have an impact in coronary artery disease. However, long-term prospective data after coronary stenting (CS) are limited. Methods Four-hundred and eighty-three consecutive patients with either stable or unstable coronary syndromes were followed for up to three years after successful CS. The composite of cardiac death, myocardial infarction or rehospitalization for rest unstable angina, whichever occurred first, was the prespecified primary end point. Moreover, the one-year incidence of clinical recurrence of symptoms, in-stent restenosis (ISR) and progression of atherosclerosis to a significant lesion (PTSL) were additionally evaluated. PTSL was defined as an increase by at least 25% in the luminal diameter stenosis of a known nonsignificant lesion (≤50% luminal diameter stenosis) that was located in a nonintervened vessel at restudy, resulting in an angiographically significant lesion (≥70% luminal diameter stenosis). Results By the end of the follow-up, high plasma levels of either CRP or Lp(a) but not tHCY were independently associated with the primary end point. In particular, CRP ≥0.68 mg/dl (p Conclusions High plasma levels of either CRP or Lp(a) but not tHCY may be associated with a higher incidence of late adverse events after successful CS. PTSL in vessels not previously intervened upon may play a significant role in the underlying pathophysiology as opposed to ISR.

Angiographic studies support an association between troponin elevation, intracoronary thrombus, and presumed embolization, but previous studies have indicated that only 20% to 25% of patients with positive troponin levels had angiographic evidence of intracoronary thrombus compared with 5% of patients who were troponin negative. 1–3 Although there already exists an association, 75% to 80% of patients with increased troponin levels had no evidence of intracoronary thrombus. It has been previously shown that the angiographic morphology of the culprit lesion in unstable angina pectoris (UAP) or non–Q-wave acute myocardial infarction (AMI) is characteristic, with 50% to 70% of patients having an acute coronary or complex lesion, which is the angiographic correlate of a disrupted or fi ssured atherosclerotic plaque and/or the presence or intracoronary thrombus. 4,5 This lesion is uncommon in culprit lesions from patients presenting with symptoms of stable angina. Therefore, it was hypothesized that this lesion classifi cation system might represent a more sensitive method for examining the association between elevated troponin and the presence of intracoronary thrombus.

Objectives The goal of this study was to investigate the dose-dependent effects of active cigarette smoking on endothelial nitric oxide (NO) and endothelin-1 (ET-1) biosynthesis. Background Limited studies have suggested that active cigarette smoking may be associated with a dose-dependent reduction of endothelium-dependent vasodilation (EDV). The underlying biochemical changes that cause this dose-specific effect, such as changes in the endothelial NO biosynthetic pathway and ET-1 production, have not been examined. Methods Flow- and nitroglycerin-mediated reactivity of the brachial artery were measured in eight nonsmokers, seven light smokers (≤1 pack/week) and eight heavy smokers (≥1 pack/day), and their sera were added to confluent (∼85%) monolayers of human umbilical endothelial cells (HUVECs) for 12 h. Basal and substance P-stimulated NO and basal ET-1 production were measured. The HUVECs used for measuring basal NO production were lysed, and both endothelial NO synthase (eNOS) protein expression and eNOS activity were determined. Results Serum cotinine level and pack-years of smoking were significantly lower in light smokers compared with heavy smokers (p Conclusions These results indicate light smoking may have similar detrimental effects on EDV and NO biosynthetic pathway as does heavy smoking. These data may have important implications concerning the amount of active cigarette exposure that imparts cardiovascular risk.

Background The mechanisms involved in the dysfunction of both endothelium-dependent vasodilatation (EDV) and NO biosynthesis related to smoking are unclear. In this study, EDV was assessed in healthy smokers and nonsmokers in vivo and, using serum from the same individuals, was related to the NO biosynthetic pathway in vitro. Methods and Results Flow-mediated EDV of the brachial artery was measured in 23 male patients (8 nonsmokers and 15 smokers). Serum was collected, added to confluent (≈85%) monolayers of human umbilical vein endothelial cells (HUVECs), and incubated for 12 hours. Basal and substance P–stimulated NO production was measured. The HUVECs used for measuring basal NO production were lysed, and both endothelial NO synthase (eNOS) protein expression and eNOS activity were determined. EDV was lower in smokers compared with nonsmokers ( P P P P P P r =0.54, P r =−0.60, P Conclusions This is the first study to combine an in vivo model with a near-physiological in vitro model to demonstrate an association between decreased NO production and reduced EDV. Cigarette smoking was associated with reduced EDV, NO generation, and eNOS activity in the presence of increased eNOS protein expression.

Background Health care workers' (HCWs) perceptions and attitudes affect implementation of precautions to prevent transmission of drug-resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA). Identification of challenges and barriers to recommended practices is a critical component of promoting a safe clinical environment of care. Methods Semistructured interviews addressed how MRSA affects HCWs, prevention of transmission, and challenges and barriers HCWs experience when entering a MRSA isolation room and performing appropriate hand hygiene. Results The purposive sample of 26 acute care HCWs (16 registered nurses; 1 physician; 6 allied health professionals; and 3 support staff) self-selected from 276 responding to a questionnaire on MRSA. Analysis identified 18 themes across seven categories. Most participants reported feeling responsible for preventing transmission, and having the knowledge and desire to do so. However, many also reported challenges to following consistent hand hygiene and use of contact precautions. Barriers included patient care demands, equipment and environmental issues such as availability of sinks, time pressures, the practices of other HCWs, and the need for additional signs indicating which patients require contact precautions. Conclusions The HCWs reported a need for improved clarity of isolation protocols throughout patients' hospital journey, additional rooms and staff for isolation patients, improved education and communication (including timely and appropriate signage), and an emphasis on involving all HCWs in reducing contamination.

Background Health care workers (HCWs) play a critical role in prevention of health care-associated infections such as methicillin-resistant Staphylococcus aureus (MRSA), but glove and gown contact precautions and hand hygiene may not be consistently used with vulnerable patients. Methods A cross-sectional survey of MRSA knowledge, attitudes/perceptions, and practices among 276 medical, nursing, allied health, and support services staff at an acute-care hospital in the eastern United States was completed in 2012. Additionally, blinded observations of hand hygiene behaviors of 104 HCWs were conducted. Results HCWs strongly agreed that preventive behaviors reduce the spread of MRSA. The vast majority reported that they almost always engage in preventive practices, but observations of hand hygiene found lower rates of adherence among nearly all HCW groups. HCWs who reported greater comfort with telling others to take action to prevent MRSA transmission were significantly more likely to self-report adherence to recommended practices. Conclusions It is important to reduce barriers to adherence with preventive behaviors and to help all HCWs, including support staff who do not have direct patient care responsibilities, to translate knowledge about MRSA transmission prevention methods into consistent adherence of themselves and their coworkers to prevention guidelines.

3:864–871. 7. Vandenberg BF, Weiss RM, Kinzey J, Acker M, Stark CA, Stanford W, Burns TL, Marcus ML, Kerber RE. Comparison of left atrial volume by two-dimensional echocardiography and cine-computed tomography. Am J Cardiol 1995;75:754–757. 8. Rodevand O, Bjornerheim R, Ljosland M, Maehle J, Smith HJ, Ihlen H. Left atrial volumes assessed by threeand two-dimensional echocardiography compared to MRI estimates. Internat J Card Imag 1999;15:397–410. 9. Patel VV, Ren J-F, Marchlinski FE. A comparison of left atrial size by transthoracic two-dimensional guided M-mode echocardiography and magnetic endocardial catheter mapping. PACE 2002;25:14–17. 10. Gepstein L, Hayam G, Ben-Hain SA. A novel method for nonfluoroscopic catheter-based electroanatomic mapping of the heart. Circulation 1997;95:1611– 1622. 11. Gepstein L, Evans SJ. Electroanatomical mapping of the heart: basic concepts and implications for the treatment of cardiac arrhythmias. PACE 1998;21:1268– 1278. 12. Pappone C, Oreto G, Lamberti F, Vicedomini G, Loricchio ML, Shpun S, Rillo M, Calabro MP, Conversano A, Ben-Haim SA, Cappato R, Chierchia S. Catheter ablation of paroxysmal atrial fibrillation using a 3D mapping system. Circulation 1997;96:2715–2721. 13. Brockenbrough EC, Braunwald E. A new technique for left ventricular angiocardiography and transseptal left heart catheterization. Am J Cardiol 1960; 6:1062–1068. 14. Wahr D, Yin SW, Schiller NB. Left ventricular volumes determined by two-dimensional echocardiography in a normal adult population. J Am Coll Cardiol 1983;1:863–868. 15. Sanfilippo AJ, Abascal VM, Sheehan M, Oertel LB, Harrigan P, Hughes RA, Weyman AE. Atrial enlargement as a consequence of atrial fibrillation: a prospective echocardiographic study. Circulation 1990;82:792–797.

The predictors of troponin release after percutaneous coronary intervention were prospectively assessed in 405 consecutive patients. Troponin release occurred frequently (27%) and was associated with complications during the procedure, including sapheneous vein graft interventions, multistent use, glycoprotein IIb/IIIa use, and a history of hypercholesterolemia.

Fifty-one patients with human immunodeficiency virus infection and acute coronary syndromes were identified. Nearly all patients (98%) had traditional coronary risk factors. Revascularization procedures were performed safely with low in-hospital mortality.

In conclusion, high plasma CRP levels are associated with more myocardial ischemia early in primary UAP. Although the underlying mechanisms are not well understood, these data could have important pathophysiologic and clinical implications. Whether the increased CRP represents a marker either for the extent of atherosclerosis or an inflammatory process in the coronary arteries or directly exerts a pro-inflammatory or prothrombotic effect on the vessel wall leading to the increased ischemia is currently unknown.

The objective of this study was to evaluate the association of high plasma levels of either C-reactive protein (CRP), lipoprotein (a) (Lp[a]) or total homocysteine (tHCY) with the long-term prognosis after successful coronary stenting (CS).High plasma levels of either CRP, Lp(a) or tHCY may have an impact in coronary artery disease. However, long-term prospective data after coronary stenting (CS) are limited.Four-hundred and eighty-three consecutive patients with either stable or unstable coronary syndromes were followed for up to three years after successful CS. The composite of cardiac death, myocardial infarction or rehospitalization for rest unstable angina, whichever occurred first, was the prespecified primary end point. Moreover, the one-year incidence of clinical recurrence of symptoms, in-stent restenosis (ISR) and progression of atherosclerosis to a significant lesion (PTSL) were additionally evaluated. PTSL was defined as an increase by at least 25% in the luminal diameter stenosis of a known nonsignificant lesion (or=50% luminal diameter stenosis) that was located in a nonintervened vessel at restudy, resulting in an angiographically significant lesion (or=70% luminal diameter stenosis).By the end of the follow-up, high plasma levels of either CRP or Lp(a) but not tHCY were independently associated with the primary end point. In particular, CRPor=0.68 mg/dl (p0.001) or Lp(a)or=25 mg/dl (p = 0.003) conferred a significantly increased risk. By 1 year, a CRPor=0.68 mg/dl conferred a significantly increased risk for clinical recurrence of symptoms (p0.001) or PTSL (p0.001). None of the studied biochemical markers was related to ISR.High plasma levels of either CRP or Lp(a) but not tHCY may be associated with a higher incidence of late adverse events after successful CS. PTSL in vessels not previously intervened upon may play a significant role in the underlying pathophysiology as opposed to ISR.

The goal of this study was to investigate the dose-dependent effects of active cigarette smoking on endothelial nitric oxide (NO) and endothelin-1 (ET-1) biosynthesis.Limited studies have suggested that active cigarette smoking may be associated with a dose-dependent reduction of endothelium-dependent vasodilation (EDV). The underlying biochemical changes that cause this dose-specific effect, such as changes in the endothelial NO biosynthetic pathway and ET-1 production, have not been examined.Flow- and nitroglycerin-mediated reactivity of the brachial artery were measured in eight nonsmokers, seven light smokers (or =1 pack/week) and eight heavy smokers (or =1 pack/day), and their sera were added to confluent ( approximately 85%) monolayers of human umbilical endothelial cells (HUVECs) for 12 h. Basal and substance P-stimulated NO and basal ET-1 production were measured. The HUVECs used for measuring basal NO production were lysed, and both endothelial NO synthase (eNOS) protein expression and eNOS activity were determined.Serum cotinine level and pack-years of smoking were significantly lower in light smokers compared with heavy smokers (p0.006 and p0.004, respectively). There were no significant differences between heavy smokers and light smokers in EDV (p = 0.52), basal- (p = 0.70) and stimulated-NO production (p = 0.95), eNOS protein (p = 0.40) and eNOS activity (p = 0.63). Compared with nonsmokers, all the parameters were significantly altered in both of the smokers' groups. No differences were found in nitroglycerin-mediated vasodilation and in vitro ET-1 production among the three groups.These results indicate light smoking may have similar detrimental effects on EDV and NO biosynthetic pathway as does heavy smoking. These data may have important implications concerning the amount of active cigarette exposure that imparts cardiovascular risk.

Background High plasma levels of C-reactive protein (CRP) are associated with shortor long-term ischemic complications in patients with unstable coronary artery disease. However, a possible direct relationship of plasma CRP with spontaneous myocardial &hernia early I” the course of non ST elevation acute coronary syndromes (NSTACS) was not thoroughly investigated. MethodsTo evaluate this issue 172 consecutive patients with NSTACS with no elevated plasma cardiac troponin T levels upon admission (cTnT-zO.1 yojdl) who underwent a 24 hour continuous IBlead electrocardiographic (ECG) monitoring were studied. The associatlon of plasma CRP levels upon admission with either the incidence or duration of the recorded myocardial ischemla (ST-segment shifts) was evaluated. Patients divided into three groups according to the tertiles of CRP values upon admission. Results During 3,696 hours of contmuous 12.lead ECG monitoring, 169 ST-segment shifts were recorded in 48 patients with a mean number of 3.5k2.0 shifts per patient and a mean duration of 29.6i23.6 min per episode, corresponding to a total duration of 124.4k143.6 mm per patlent. There was a significant gradual increased risk for either the incidence (p