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Background: Peripheral arterial disease (PAD) was reported to increase the risk of new cardiovascular events in patients with acute coronary syndromes (ACS). However, most of the evidence comes from randomized clinical trials. We aimed to assess the impact of PAD on cardiovascular outcome and treatment decisions in ACS patients in a current real-life setting. Methods: START-ANTIPLATELET is a multicenter registry enrolling ACS patient. Baseline clinical characteristics and treatment at discharge were recorded and follow-up was repeated at 6-months and 1-year. PAD was defined as intermittent claudication and/or previous revascularization. Results: Among 1442 patients enrolled, 103 (7.1%) had PAD. PAD patients were older (71.8 ± 10.6vs66.2 ± 12.6 yrs., p < 0.0001), more frequently hypertensive (90.3vs68.6%, p< 0.0001), hypercholesterolemic (66vs52%, p= 0.037), diabetic (51.5vs24%, p= 0.0001), obese (28.2vs19.3%, p= 0.029) and with previous TIA (7.8vs2.8%, p= 0.005) or stroke (11.7vs3.1%, p< 0.0001). Clinical presentation and acute treatment were similar in non-PAD and PAD patients, but the latter were discharged significantly less frequently on dual antiplatelet therapy (DAPT) (68.9vs85%, p= 0.005). After a median follow-up time of 11.1 months, major cardio/cerebrovascular event-free survival [MACCE, including cardiovascular death, MI, TIA and stroke, target-vessel revascularization (TVR) and major arterial ischemic events] was significantly shorter (9.0vs11.2 months, p= 0.02; HR 3.2, 2.4–8.4) in PAD patients and net adverse cardiovascular events (NACE = MACCE plus major hemorrhages) were significantly more frequent (19.1%vs10.5%, p = 0.049). Conclusions: PAD identifies a subgroup of ACS patients at significantly increased cardiovascular risk, but these patients tend to be undertreated. Patients admitted for ACS should be screened for PAD and optimal medical therapy at discharge should be implemented.

Objectives CD40 ligand (CD40L), a transmembrane glycoprotein belonging to the tumor necrosis factor family and expressed by a variety of cells, is involved in the basic mechanisms of inflammation, atherosclerosis and thrombosis. Some studies suggest that the soluble form of CD40L (sCD40L) is a predictor of major cardiovascular events and mortality in a variety of clinical settings, but data from literature are conflicting. Methods We studied consecutive patients with acute (ACS) or chronic (CCS) coronary syndrome who underwent percutaneous coronary artery intervention (PCI). Blood samples for sCD40L dosage were taken at baseline immediately before PCI. We tested the relation between sCD40L and pre-specified outcome measures consisting of new ACS, clinical restenosis and all-cause mortality. We recruited 3,841 patients (mean age 64 ± 11 years, 79% men) with ACS (n=2,383) or CCS (n=1,458). Results During a mean follow-up of two years (±0.6 years), 642 patients developed ACS, 409 developed restenosis (≥70% of at least one of the previously treated coronary segments) and 175 died. For each 1-standard deviation increase in sCD40L (0.80 ng/mL), the hazard ratios (HRs) for ACS, restenosis, and mortality were 1.11 (95% confidence interval [CI]: 1.05 to 1.18, p Conclusions Among patients with ACS or CCS who undergo PCI, higher levels of sCD40L predict an increased risk of acute coronary events and coronary restenosis, but not of mortality.

Background Hypertension is characterised by a high prevalence, low awareness and poor control among rheumatoid arthritis (RA) patients. Correct blood pressure (BP) measurement is highly important in these subjects. The “unattended” BP measurement aims to reduce the “white-coat effect,” a phenomenon associated with cardiovascular risk. Data on “unattended” BP measurement in RA and its impact on hypertensive organ damage are very limited. Methods BP was measured in the same patient both traditionally (“attended” BP) and by the “unattended” protocol (3 automated office BP measurements, at 1-min intervals, after 5 min of rest, with patient left alone) by a randomised cross-over design. Patients underwent clinical examination, 12-lead electrocardiography and trans-thoracic echocardiography to evaluate cardiac damage. Results Sixty-two RA patients (mean age 67 ± 9 years, 87% women) were enrolled. Hypertension was diagnosed in 79% and 66% of patients according to ACC/AHA and ESC/ESH criteria, respectively. Concordance correlation coefficients between the two techniques were 0.55 (95%, CI 0.38–0.68) for systolic BP and 0.73 (95%, CI 0.60–0.82) for diastolic BP. “Unattended” (121.7/68.6 mmHg) was lower than “attended” BP (130.5/72.8 mmHg) for systolic and diastolic BP (both p

Stable ischaemic heart disease is a frequent and very heterogeneous condition. Drug therapy is important, in these patients, for improving their prognosis and controlling their symptoms. The typical clinical manifestation of obstructive coronary disease is angina pectoris. This symptom can be improved by various classes of compounds, namely beta-blockers (BBs), calcium antagonist, and nitrates. More recently, ranolazine and ivabradine have been introduced. All these drugs have been proven to reduce significantly angina. On the other hand, there are no evidences supporting improvement in prognosis, besides for the use of BBs, in patients with previous myocardial infarction (MI) or systolic dysfunction. Besides drugs for symptoms control, these patients also receive antiplatelet drugs, specifically aspirin, and lipid lowering compounds such as statins. Furthermore, recent evidences supported the use of low doses direct anticoagulant, or a second antiplatelet agent in patients with previous MI. Similarly, a very low LDL cholesterol level, such as obtained with PCKS9 inhibitors, seems very beneficial in these patients. It is possible that in the near future a specific role for neo-angiogenesis factors and cellular therapies, could be proven, albeit, presently these treatments are not supported by solid evidences.

This paper proposes a methodology to design the biomethane production chain from MSW at the regional level and to assess the environmental and economic performance of the chain. In the design phase, the following parameters are considered: number and production capacity of biomethane plants, localization of plants, waste flows among municipalities and plants. The model is adopted to design the biomethane chain in the Rome Metropolitan Area (Italy). Several structures of production chain are designed and their performances are assessed. The economic factors mostly able to affect the performance of the chain are waste disposal tariff, biomethane selling price, and the economic incentive provided to biomethane producers. Their impacts are discussed through sensitivity analyses. Results show that the structure maximizing the economic performance has the worst environmental performance and vice versa. Hence, a new structure of the economic incentive is proposed, aimed at re-aligning economic and environmental performance.

For many years, β-blockers have been considered contraindicated in patients with heart failure (HF) and in those with bronchial asthma or even chronic obstructive pulmonary disease (COPD) although without clear evidence of asthma. Today, despite overwhelming evidence of the usefulness of β-blockers, especially in HF with reduced left ventricular ejection fraction (HFrEF), and in ischaemic heart disease, some reluctance persists in using these drugs when COPD coexists. Such resistance is due to the fear that a possible worsening of bronchospasm induced by β-blockers could induce negative effects greater than the benefits. The Guidelines of the European Society of Cardiology clearly suggest that: (i) implantation of a cardiac defibrillator (ICD) are not contraindicated in COPD without clear evidence of bronchial asthma; (ii) β-blockers are only ‘relatively’ contraindicated when there is certainty of bronchial asthma with a documented bronchodilator response to the β2 stimulant. Therefore, bronchial asthma is not an absolute contraindication to β-blockers. The cardiologist should not limit the diagnosis of COPD to clinical suspicion, but should rely on a spirometry examination associated with any bronchodilation tests. In any case, selective β1 blockers are preferred, starting at a basic dose, which ensure a better dilator response to bronchodilators and in any case cause less bronchospasm than non-selective β-blockers. Unfortunately, there is still some reluctance to the use of β-blockers in patients with COPD associated with HF, which should be eliminated.

Fluoroscopic criteria have been described for the documentation of septal right ventricular (RV) lead positioning, but their accuracy remains questioned. Consecutive patients undergoing pacemaker or defibrillator implantation were prospectively included. RV lead was positioned using postero-anterior and left anterior oblique 40° incidences, and right anterior oblique 30° to rule out coronary sinus positioning when suspected. RV lead positioning using fluoroscopy was compared to true RV lead positioning as assessed by transthoracic echocardiography (TTE). Precise anatomical localizations were determined with both modalities; then, RV lead positioning was ultimately dichotomized into two simple clinically relevant categories: RV septal or RV free wall. Accuracy of fluoroscopy for RV lead positioning was then assessed by comparison with TTE. We included 100 patients. On TTE, 66/100 had a septal RV lead and 34/100 had a free wall RV lead. Fluoroscopy had moderate agreement with TTE for precise anatomical localization of RV lead (k = 0.53), and poor agreement for septal/free wall localization (k = 0.36). For predicting septal RV lead positioning, classical fluoroscopy criteria had a high sensitivity (95.5%; 63/66 patients having a septal RV lead on TTE were correctly identified by fluoroscopy) but a very low specificity (35.3%; only 12/34 patients having a free wall RV lead on TTE were correctly identified by fluoroscopy). Classical fluoroscopy criteria have a poor accuracy for identifying RV free wall leads, which are most of the time misclassified as septal. This raises important concerns about the efficacy and safety of RV lead positioning using classical fluoroscopy criteria.

Background: Classical fluoroscopic criteria for the documentation of septal right ventricular (RV) lead positioning have poor accuracy. We sought to evaluate the individualized left anterior oblique (LAO) projection as a novel fluoroscopy criterion. Methods: Consecutive patients undergoing pacemaker or defibrillator implantation were prospectively included. RV lead positioning was assessed by fluoroscopy using posteroanterior, right anterior oblique 30° to rule out coronary sinus positioning, and LAO 40° in the classical group or individualized LAO in the individualized group. Individualized LAO was defined by the degree of LAO that allowed the perfect superposition of the RV apex (using the tip of the RV lead temporarily placed at the apex) and of the superior vena cava-inferior vena cava axis (materialized by a guidewire), hence providing a true profile view of the interventricular septum. Accuracy of fluoroscopy for RV lead positioning was then assessed by comparison with true RV lead positioning using transthoracic echocardiography. Results: We included 100 patients, 50 in each study group. Agreement between RV lead septal/free wall positioning in transthoracic echocardiography and fluoroscopy was excellent in the individualized group (k=0.91), whereas it was poor in the classical group (k=0.35). Septal/free wall RV lead positioning was correctly identified in 48/50 (96%) patients in the individualized group versus 38/50 (76%) in the classical group ( P =0.004). For septal lead positioning, fluoroscopy had 100% Se and 89.5% Sp in the individualized group versus 91.4% Se and 40% Sp in the classical group. Complications and procedural data were comparable in both groups. Conclusion: Individualized LAO is a quick and highly reliable patient-tailored fluoroscopy projection for RV lead positioning.

Background Cardiac resynchronization therapy optimization can be pursued by left ventricular pacing vector selection and atrioventricular (AV) and interventricular (VV) delays optimization. The combination of these methods and its comparison with multipoint pacing (MPP) is scarcely studied. Methods Using noninvasive cardiac output (CO) measurement, the best of five left ventricular pacing vectors was determined, then AV and VV delays optimization was applied on top of the best vector. Response to the optimization protocol was defined as a >5% CO increase compared to the standard biventricular configuration. Results Twenty-two patients (18 men, age 71 ± 9 years) were included. Standard biventricular configuration increased CO compared to baseline (4.65 ± 1.55 L/min vs 4.27 ± 1.53 L/min, respectively, P = 0.02). The best quadripolar configuration increased CO to 4.85 ± 1.67 L/min (P = 0.03 compared to the standard biventricular configuration). AV then VV delay optimization both provided additional benefit (final CO 5.56 ± 2.03 L/min, P = 0.001 compared to the best quadripolar configuration). Fifteen (68%) patients responded to the optimization protocol. Anatomical MPP (based on maximal anatomical separation between electrodes) and electrical MPP (based on maximal electrical activation difference between electrodes) were evaluated in 16 patients and yielded a CO similar to that of the optimization procedure. Conclusions The combination of choosing the best quadripolar pacing configuration and optimizing atrioventricular and interventricular delays resulted in an improvement of cardiac output compared to standard biventricular stimulation in 68% of patients. The final cardiac output was comparable to multipoint pacing.

Background— In heart failure (HF) with reduced ejection fraction, right ventricular (RV) impairment, as defined by reduced tricuspid annular plane systolic excursion, is a predictor of poor outcome. However, peak longitudinal strain of RV free wall (RVFWS) has been recently proposed as a more accurate and sensitive tool to evaluate RV function. Accordingly, we investigated whether RVFWS could help refine prognosis of patients with HF with reduced ejection fraction in whom tricuspid annular plane systolic excursion is still preserved. Methods and Results— A total of 200 patients with HF with reduced ejection fraction (age, 66±11 years; ejection fraction, 30±7%) with preserved tricuspid annular plane systolic excursion (>16 mm) underwent RV function assessment using speckle-tracking echocardiography to measure peak RVFWS. After a median follow-up period of 28 months, 62 (31%) patients reached the primary composite end point of all-cause death/HF rehospitalization. Median RVFWS was −19.3% (interquartile range, −23.3% to −15.0%). By lasso-penalized Cox-hazard model, RVFWS was an independent predictor of outcome, along with Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure-HF score, Echo-HF score, and severe mitral regurgitation. The best cutoff value of RVFWS for prediction of outcome was −15.3% (area under the curve, 0.68; P P P Conclusions— In patients with HF with reduced ejection fraction with preserved tricuspid annular plane systolic excursion, RV free-wall strain provides incremental prognostic information and improved risk stratification.

There is little doubt that, in the last twenty years' discussion, the historical culture of industrial design has made a significant contribution to put important theoretical issues into focus; first of all, that of the definition of the discipline and its field of action. I am thinking of, for example, the debate conducted in publications and periodicals,2 the birth of associations, the multiplication of opportunities for international encounters,3 exhibitions, and events in museums. These phenomena are familiar to all, so there is no reason to discuss them at length here. As often has been the case for other areas of study, historical research has turned out to be a preliminary, basic condition for the very nature of industrial design as a culture, a context, and a discipline. Without attempting to retrace the fertile discussion that has taken place on an international level, we should at least mention that the results achieved have been very useful in a wide range of directions, especially for the identification of prevailing historiographic models, the identification of new ones, the expansion of the area of investigation,4 and the refinement of research methods. And while many, perhaps a great many, fields have yet to be explored or have been overlooked, many new perspectives have appeared. I would like to briefly indicate at least three points I feel emerge more than others, and that, in my opinion, are crucial: the relationship between historical research and design research; innovation as a key of interpretation both for history and for design activity; and the role of historical research for design. As we can see, these are wide-ranging arguments. What prompts me to discuss such themes is not the pretense of providing in-depth insight each of them. The fact of the matter is that they are closely interconnected; only their mutual interrelations can give a complete sense to my line of reasoning. Therefore, all I can do is to develop, for each of them, a few lines of working investigation (which have emerged in my work first in the doctoral program, then in teaching and research activities in the Industrial Design course of the Politecnico of Milan), illustrating their points of contact and cross-fertilization. 1 Raymond Queneau, Una storia modello (1966) (Torino: Einaudi, 1988), 6-7. 2 Although it is familiar ground, I would like to recall the important role in the design history debate played, in the past and present, by magazines such as Industrial Design, Stile Industria, Design Issues, Design Studies, Joumal of Design History, and Culture Technique. (some of which still exist, fortunately). Here, I would like to call the reader's attention above all to Design Issues of Spring 1995, entirely devoted to the question of the history of industrial design. In my opinion, it represents an indispensable turning point for the theme discussed here. 3 After the first Convegno internazionale di studi storici sul design held at the Politecnico of Milan, 1991, we can mention the first International Conference on Design History and Design Studies, "Design History Seen From Abroad: History and Histories of Design," Barcelona, 5th Spring of Design, 1999 April 26-28. and the Second Scientific Meeting of Design Historians and Scholars, Havana, June 2000. 4 1 am thinking of the fundamental area of the history of visual design, connected in an increasingly aware manner to the history of products, companies, and institutions; autonomous co-protagonist of a design situation in which certain sectors are encountering a blurring of the boundaries between product design and graphic design. But I am also thinking about the emergence of the historiography of "peripheral countries" and the questions it raises concerning the dominant, AngloSaxon approach to historiography. ? Copyright 2001 Massachusetts Institute of Technology 24 Design Issues: Volume 17, Number 4 Autumn 2001

Objective The objective of this study was to report the effects of Terlipressin treatment in 2 potential organ donors with intractable, catecholamine-resistant hypotension. Design and Setting This study was based on case reports in the intensive care unit of a general hospital. Patients Patients included 2 adult patients with cerebral death and catecholamine-resistant hypotension. Interventions A low dose of Terlipressin (3.5 μg/kg) by intravenous bolus was added to the standard treatment. Measurement and Results In both cases, Terlipressin induced a rapid improvement in arterial pressure with a consequent increase in urine output and the appearance of diabetes insipidus. In 1 patient it allowed for the withdrawal of norepinephrine infusion. No related adverse effects were detected in either patient. Organ removal was not possible in the second case due to lack of family consent. Conclusions Terlipressin might be considered as a rescue therapy for potential organ donors with intractable, catecholamine-resistant hypotension. In spite of the positive results obtained here and by other authors in the treatment of septic shock, its judicious use is recommended, and an optimal administration schedule must still be elucidated.

We present a method for the evaluation, at the first level of trigger, of logical conditions with high time resolution, using the digitized times of fast signals delivered in the detectors of high rate experiments. We describe a dead-time-less implementation of this method on a commercial Field Programmable Gate Array (FPGA). By virtue of its features, the method offers an excellent solution to the problem of including veto conditions in the first level of trigger for experiments on rare decays., Comment: 14 pages with 7 figures, accepted to be published in NIM A