Effectiveness of primary percutaneous coronary intervention for acute ST-elevation myocardial infarction from a 5-year single-center experience

Primary percutaneous coronary intervention (PCI) is currently viewed as the preferred reperfusion strategy in patients with ST-elevation acute myocardial infarction (STEMI). This method was introduced in our hospital in 2000. From January 1, 2000, to December 31, 2004, a total of 2,393 consecutive patients with STEMI were admitted (27% transferred from 9 non-PCI hospitals and 31 prehospital emergency units/outpatient clinics). Of these patients, 1,666 (70%) underwent urgent coronary angiography and primary PCI. Platelet glycoprotein llb/llla inhibitors were used in 40% and stent placement, in 78%. Postprocedural Thrombolysis In Myocardial Infarction (TIMI) 3 flow was documented in 86%. Intra-aortic balloon counterpulsation was used in 6%; mechanical ventilation, in 8.6%; and inotropic drugs/vasopressors, in 15.8%. Mortality rates in patients with Killip's class I or II ranged from 1% to 4.9% without negative influence of ischemic time. In patients with Killip's class III or IV, mortality rates increased from 18% to 54% with increasing ischemic delay up to 6 hours (p = 0.06) and remained at around 40% afterward. Independent predictors of mortality were age (odds ratio [OR] 1.29, 95% confidence interval [CI] 1.01 to 1.64, p = 0.04), resuscitated cardiac arrest (OR 2.44, 95% CI 1.18 to 5.05, p = 0.02), and postprocedural TIMI flow (OR 0.31, 95% CI 0.16 to 0.59). Overall mortality rates of patients who underwent a primary PCI strategy from 2000 to 2004 were significantly lower than in the control group of 152 consecutive patients who underwent thrombolysis from 1995 to 1996 (6.2% vs 16.4%; p <0.001). In conclusion, introduction of a primary PCI strategy significantly decreased hospital mortality in our unselected group of patients with STEMI compared with the thrombolytic era. Our study further emphasized the importance of shortening myocardial ischemic time, particularly in the presence of severe heart failure on admission.     

Liposomal daunorubicin versus standard daunorubicin: long term follow-up of the GIMEMA GSI 103 AMLE randomized trial in patients older than 60 years with acute myelogenous leukaemia

This randomized phase III clinical trial explored the efficacy of DaunoXome (DNX) versus Daunorubicin (DNR) in acute myeloid leukaemia (AML) patients aged >60 years. Three hundred and one AML patients were randomized to receive DNR (45 mg/m(2) days 1-3) or DNX (80 mg/m(2) days 1-3) plus cytarabine (AraC; 100 mg/m(2) days 1-7). Patients in complete remission (CR) received a course of the same drugs as consolidation and then were randomized for maintenance with AraC+ all trans retinoic acid or no further treatment. Among 153 patients in the DNR arm, 78 (51.0%) achieved CR, 55 (35.9%) were resistant and 20 (13.1%) died during induction. Among 148 patients in the DNX arm, 73 (49.3%) achieved CR, 47 (31.8%) were resistant and 28 (18.9%) died during induction. Univariate analysis showed no difference as to induction results. After CR, DNX showed a higher incidence of early deaths (12.5% vs. 2.6% at 6 months, P = 0.053) but a lower incidence of relapse beyond 6 months (59% vs. 78% at 24 months, P = 0.064), with a cross in overall survival (OS) and disease-free survival (DFS) curves and a later advantage for DNX arm after 12 months from diagnosis. DNX seems to improve OS and DFS in the long-term follow-up, because of a reduction in late relapses.     

Pharmacological modulation of the hyperpolarization-activated current (I f) in human atrial myocytes: focus on G protein-coupled receptors

AIMS: In human atrial myocytes (HuAM) two beta-adrenergic receptors (beta-AR) and four splicing-variants of the serotonin 5-HT(4) receptor are present. Multiple coupling with G stimulatory (G(s)) and G inhibitory (G(i)) proteins has been proposed for both beta(2)-AR and 5-HT((4b)) subtypes, but no functional data exist in HuAM. Serotonin (5-HT) and catecholamines are able to trigger arrhythmias in human atrium, but the underlying cellular mechanisms are not completely understood. The pacemaker current (I(f)) is an inward Na(+)/K(+) current, constitutively present in HuAM and directly modulated by cAMP; I(f) could play a role in triggering human atrial arrhythmias. This study evaluated the different G protein coupling of beta(1)-AR, beta(2)-AR and 5-HT(4) receptors by assessing the modulation of I(f) by selective stimuli. METHODS: HuAM were isolated from right atrial appendages and utilized for patch-clamp recording. The coupling of receptor subtypes with G(i) proteins was tested by incubating HuAM in pertussis toxin (PTX). RESULTS: Beta(1)-AR stimulation (Isoprenaline [ISO] + ICI 118,551), and 5-HT caused a concentration-dependent significant shift of the half activation potential of I(f) activation curve (DeltaV(h)), P < 0.01. beta(2)-AR stimulation (ISO 1 microM + CGP 20712A) also significantly shifted V(h) (P < 0.0001), but with DeltaV(h)[beta(2)-AR] significantly smaller than the effect caused by 1 microM beta(1)-AR stimulation (P < 0.05). Pre-treatment of HuAM with PTX did not alter the effect of beta(1)-AR stimulation (both 0.1 and 1 microM) and 1 microM 5-HT on I(f), but significantly increased the effect in response to beta(2)-AR stimulation and 0.1 microM 5-HT (P < 0.05 for both), thus suggesting a G(i) protein coupling of these receptors. CONCLUSIONS: Our results provide the first functional evidence of the different G protein coupling of beta(1)-AR, beta(2)-AR and 5-HT(4) receptors in HuAM. Further they support the view that I(f) current might play an important role in triggering catecholamines and serotonin-induced atrial arrhythmias.     

Transnasal transesophageal echocardiography: A new approach for the PFO occlusion in awake patients

Objectives : To reduce risks, discomfort, cost, and operative time for percutaneous patent foramen ovale (PFO) closure, we propose to perform this procedure under transesophageal echo‐guidance using a 10 Fr. catheter introduced through nasal way (TEENW). Background : Transesophageal or intracardiac echocardiography is commonly used to guide percutaneous PFO closure. Sedation needed quite frequently during transesophageal echocardiography, increased patients' discomfort, procedure prolongation, costs, use of both femoral veins, and additional intracardiac manipulations are the main limitations of standard techniques. Methods : We enrolled 20 consecutive patients with a history of cerebral ischemia and PFO with right‐to‐left shunt. In 15 patients Amplatzer® PFO occluder was used, whereas in five patients with longer PFO tunnel (>10 mm) Cardia Intrasept® was selected. Without sedation, a multifrequency monoplane probe, developed for intracardiac echocardiography, was introduced into the nostril and advanced forward the esophagus. Then under echo guidance, the closing device was presented, opened and released. Results : Procedure lasted for an average of 33.3 min, and no complications were seen. At procedure's completion, six patients showed persistence of reduced shunt during Valsalva manoeuvre. At six‐month follow‐up, shunts disappeared in all patients. Conclusion : TEENW is safe and well tolerated, and images' quality is high enough to deserve widespread adoption of this technique for PFO closure. © 2008 Wiley‐Liss, Inc.     

Depressive symptoms as risk factor of cardiovascular mortality in older European men: the Finland, Italy and Netherlands Elderly (FINE) study.

BACKGROUND: Depressive symptoms have been suggested to increase the risk of cardiovascular diseases, but this may reflect reversed causality. We investigated to what extent depressive symptoms are a true risk factor for cardiovascular mortality in elderly men. DESIGN: The Finland, Italy and Netherlands Elderly (FINE) study is a prospective cohort study conducted in Finland, Italy and The Netherlands. METHODS: Depressive symptoms were measured with the Zung self-rating Depression Scale in 799 elderly men, aged 70-90 years, free from cardiovascular diseases. Using Cox models, hazard ratios (HRs) were calculated for specific cardiovascular mortality endpoints. The analyses were adjusted for potential confounders, stratified on country and repeated after exclusion of men who died from cardiovascular diseases up to 5 years after baseline. RESULTS: During 10-years of follow-up 224 (28%) men died from cardiovascular diseases. The adjusted hazard for a five-point increase in depressive symptoms was 1.15 [95% confidence interval (CI) 1.08-1.23] for cardiovascular mortality. This risk was stronger for mortality from stroke (HR 1.35; 95% CI 1.19-1.53) and heart failure (HR 1.16; 95% CI 1.00-1.35) in comparison with mortality from coronary heart disease (HR 1.08; 95% CI 0.97-1.20) and other degenerative heart diseases (HR 1.06; 95% CI 0.91-1.23). Exclusion of men who died from cardiovascular diseases within 5 years after baseline did not change the strength of the associations. There were no significant differences in HRs between northern and southern Europe. CONCLUSIONS: This study provides further and more convincing prospective evidence for depressive symptoms as a risk factor for cardiovascular mortality in elderly men.     

Clinical impact of direct referral to primary percutaneous coronary intervention following pre-hospital diagnosis of ST-elevation myocardial infarction.

AIMS: Treatment delay is a powerful predictor of survival in ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI). We investigated effectiveness of pre-hospital diagnosis of STEMI with direct referral to PCI, alongside more conventional referral strategies. METHODS AND RESULTS: From January 2003 to December 2004, 658 STEMI patients were referred for primary PCI at our intervention laboratory. Three predefined referral routes were compared: (1) for patients within 90 min drive of the PCI centre, pre-hospital diagnosis and direct transportation (n=166), (2) diagnosis at the interventional hospital emergency department (n=316), (3) diagnosis at local hospitals before transportation (n = 176). Pre-hospital diagnosis was associated with more than 45 min reduction in treatment delay (P = 0.001). No significant difference in in-hospital mortality was apparent in the overall study population. In the cardiogenic shock subgroup (n = 80), pre-hospital diagnosis was associated with a two-thirds reduction in in-hospital mortality (P = 0.019); mortality was only 6.2% in shock patients who underwent PCI in < 2 h. CONCLUSION: This study shows that pre-hospital diagnosis can provide a reduction in primary PCI treatment delay, and suggests the hypothesis that this referral strategy might provide survival benefits to patients with cardiogenic shock.     

Smart Drugs and Synthetic Androgens for Cognitive and Physical Enhancement: Revolving Doors of Cosmetic Neurology

Cognitive enhancement can be defined as the use of drugs and/or other means with the aim to improve the cognitive functions of healthy subjects in particular memory, attention, creativity and intelligence in the absence of any medical indication. Currently, it represents one of the most debated topics in the neuroscience community. Human beings always wanted to use substances to improve their cognitive functions, from the use of hallucinogens in ancient civilizations in an attempt to allow them to better communicate with their gods, to the widespread use of caffeine under various forms (energy drinks, tablets, etc.), to the more recent development of drugs such as stimulants and glutamate activators. In the last ten years, increasing attention has been given to the use of cognitive enhancers, but up to now there is still only a limited amount of information concerning the use, effect and functioning of cognitive enhancement in daily life on healthy subjects. The first aim of this paper was to review current trends in the misuse of smart drugs (also known as Nootropics) presently available on the market focusing in detail on methylphenidate, trying to evaluate the potential risk in healthy individuals, especially teenagers and young adults. Moreover, the authors have explored the issue of cognitive enhancement compared to the use of Anabolic Androgenic Steroids (AAS) in sports. Finally, a brief overview of the ethical considerations surrounding human enhancement has been examined.