Renin-Angiotensin-Aldosterone System Inhibitors, Statins, and Beta-Blockers in Diabetic Patients With Critical Limb Ischemia and Foot Lesions

Medical therapy for secondary prevention is known to be under-used in patients with peripheral artery disease (PAD). Few data are available on the subgroup with critical limb ischemia (CLI). Prescription of cardiovascular preventive therapies was recorded at discharge in a large, prospective cohort of patients admitted for treatment of CLI and foot lesions, stratified for coronary artery disease (CAD) diagnosis. All patients were followed up for at least 1 year. The primary endpoint was major adverse cardiovascular events (MACE). 618 patients were observed for a median follow-up of 981 days. Renin-angiotensin-aldosterone system (RAAS) inhibitors, statins, beta-blockers, and antithrombotic drugs were prescribed in 52%, 80%, 51%, and 99% of patients, respectively. However, only 43% of patients received optimal medical therapy (OMT), defined as the combination of RAAS inhibitor plus statin plus at least one antithrombotic drug. It was observed that the prescription of OMT was not affected by the presence of a CAD diagnosis. On the other hand, it was noticed that the renal function affected the prescription of OMT. OMT was independently associated with MACE (HR 0.688, 95%CI 0.475-0.995, P = .047) and, after propensity matching, also with all-cause mortality (HR 0.626, 95%CI 0.409-0.958, P = .031). Beta-blockers prescription was not associated with any outcome. In conclusion, patients with critical limb ischemia are under-treated with cardiovascular preventive therapies, irrespective of a CAD diagnosis. This has consequences on their prognosis

The impact of sex and physical performance on long-term mortality in older patients with myocardial infarction

Background: Sex influences outcome of patients with acute coronary syndrome (ACS). If there is a relationship between sex and physical performance is unknown. Methods: The analysis is based on older (≥70 years) ACS patients included in the FRASER, HULK, and LONGEVO SCA prospective studies. Physical performance was assessed by Short Physical Performance Battery (SPPB). The primary outcome was all-cause mortality. Results: The study included 1388 patients, and 441 (32%) were women. At presentation, women were older and more compromised than men. After a median follow-up of 998 [730-1168] days, all-cause death occurred in 334 (24.1%) patients. At univariate analysis, female sex was related to increased risk of death. After adjustments for confounding factors, female sex was no longer associated with mortality. Women showed poor physical performance compared with men (p < 0.001). SPPB values emerged as an independent predictor of death. Including clinical features and SPPB in the multivariable model, we observed a paradigm shift in the prognostic role of female sex that becomes a protective factor (HR 0.73, 95% CI 0.56-0.96). Sex and physical performance showed a significant interaction (p = 0.03). For lower SPPB values (poor physical performance), sex-related changes in mortality were not recorded, while in patients with higher SPPB values (preserved physical performance), female sex was associated with better survival. Conclusions: Two key findings emerged from the present real-life cohort of older ACS patients: (i) physical performance strongly influences long-term mortality; (ii) women with preserved physical performance have a better outcome compared to me

Clinical governance of patients with acute coronary syndromes

Aims Using the principles of clinical governance, a patient-centred approach intended to promote holistic quality improvement, we designed a prospective, multicentre study in patients with acute coronary syndrome (ACS). We aimed to verify and quantify consecutive inclusion and describe relative and absolute effects of indicators of quality for diagnosis and therapy. Methods and results Administrative codes for invasive coronary angiography and acute myocardial infarction were used to estimate the ACS universe. The ratio between the number of patients included and the estimated ACS universe was the consecutive index. Co-primary quality indicators were timely reperfusion in patients admitted with ST-elevation ACS and optimal medical therapy at discharge. Cox-proportional hazard models for 1-year death with admission and discharge-specific covariates quantified relative risk reductions and adjusted number needed to treat (NNT) absolute risk reductions. Hospital codes tested had a 99.5% sensitivity to identify ACS universe. We estimated that 7344 (95% CI: 6852-7867) ACS patients were admitted and 5107 were enrolled-i.e. a consecutive index of 69.6% (95% CI 64.9-74.5%), which varied from 30.7 to 79.2% across sites. Timely reperfusion was achieved in 22.4% (95% CI: 20.7-24.1%) of patients, was associated with an adjusted hazard ratio (HR) for 1-year death of 0.60 (95% CI: 0.40-0.89) and an adjusted NNT of 65 (95% CI: 44-250). Corresponding values for optimal medical therapy were 70.1% (95% CI: 68.7-71.4%), HR of 0.50 (95% CI: 0.38-0.66), and NNT of 98 (95% CI: 79-145). Conclusion A comprehensive approach to quality for patients with ACS may promote equitable access of care and inform implementation of health care delivery. Registration ClinicalTrials.Gov ID NCT0425553

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Verso un protocollo di Antimicrobial Stewardship per le urosepsi

In ambito ospedaliero e comunitario, le infezioni delle vie urinarie (IVU) sono tra le più comuni patologie infettive e sono responsabili del frequente ricorso ad esami diagnostici, alla prescrizione di antibiotici e, più in generale, incidono sulla qualità di vita dei pazienti. Per quanto frequenti, sono patologie difficili da delineare, con molteplici sfaccettature e diversi gradi di severità, che spaziano dalle IVU non complicate fino alle IVU complicate e alle urosepsi. Questo studio condotto su 95 pazienti con sepsi a partenza dalle vie urinarie durante un periodo di otto mesi (da Febbraio a Settembre 2016) rappresenta la fase preliminare all’introduzione di un programma di Antimicrobial Stewardship (ASP) nella realtà locale dei reparti di Medicina Interna dell’Ospedale “F. Lotti” di Pontedera (PI). Inizialmente sono state analizzate le caratteristiche clinico-epidemiologiche e microbiologiche dei pazienti in studio, quali età e fattori di rischio (FR) per lo sviluppo di urosepsi e di antibiotico-resistenza, ma anche i parametri clinici all’esordio del quadro infettivo. È emerso che queste patologie affliggono una tipologia di paziente prevalentemente anziano, con molteplici fattori di rischio (i pazienti con almeno un FR sono ben l’86% del totale) e spesso portatore di numerose altre patologie. Lo studio ha dimostrato che le urosepsi sono affezioni frequenti nei reparti di Medicina Interna (il loro tasso d’incidenza è vicino a 4.15 casi/100 ricoveri), determinano una lunga degenza (almeno 9 giorni) e si caratterizzano per una significativa mortalità (che si attesta intorno all’8.5%). Le condizioni cliniche all’esordio sono caratteristiche: questi pazienti si presentano spesso in shock, con leucocitosi neutrofila, alta concentrazione sierica di PCT e PCR e con una funzione renale peggiorata, anche in assenza di pregressa insufficienza renale. Pertanto queste patologie non sono difficili da diagnosticare e sulla loro gestione iniziale si gioca buona parte del successo terapeutico successivo. Lo studio ha infatti messo in evidenza il ruolo cruciale della raccolta di campioni biologici per esami colturali già in Pronto Soccorso, che permette di modificare precocemente la terapia empirica iniziale a favore di una mirata ai risultati in vitro, una volta che il paziente viene trasferito in reparto. Successivamente sono stati individuati otto indicatori di qualità gestionale - validati in letteratura – di cui è stata valutata l’applicazione nella realtà in studio; questi sono stati poi utilizzati per teorizzare una serie di interventi efficaci e mirati al miglioramento dell’intero percorso terapeutico e che sono confluiti in un programma interno di Antimicrobial Stewardship. Dallo studio retrospettivo è emerso che la percentuale di applicazione di questi indicatori è stata variabile, passando dal 25% al 100%: più in dettaglio, l’esecuzione dell’urinocoltura nei pazienti con urosepsi ha avuto una percentuale di applicazione del 90%, la prescrizione antibiotica empirica in accordo con le linee guida nazionali è stata applicata nel 100% dei casi, l’uso di fluorochinoloni solo come terapia orale nel 27%, la modifica della terapia empirica dopo i risultati delle colture nel 38%; e ancora la variazione della terapia intravenosa in terapia orale dopo 48-72 h in base alle condizioni cliniche nel 17%, la durata della terapia antibiotica di almeno 10 giorni nel 73%, la sostituzione del catetere entro 24h dall’inizio del trattamento antibiotico nel 32% ed infine l’adattamento della dose degli antibiotici in relazione alla funzione renale in tutti i casi esaminati. Data la frequenza delle IVU, e delle urosepsi, queste affezioni concorrono in maniera significativa al consumo totale degli antibiotici, con incremento della spesa sanitaria e della diffusione dell’antibiotico-resistenza: proprio quest'ultimo fenomeno appare in netta crescita tra i microrganismi responsabili di urosepsi, come è stato messo in evidenza dal confronto tra i dati di antibiotico resistenza regionali (Secondo Report della Rete di Sorveglianza dell’antibiotico-resistenza in Toscana - SART-) e quelli derivati dal nostro studio, soprattutto per quanto riguarda E. coli, E. faecalis, P. aeruginosa e K. Pneumoniae – che sono tra i microrganismi più spesso responsabili di urosepsi -. L'elevata percentuale di resistenza agli antibiotici comunemente utilizzati in terapia antibiotica empirica, e come tali consigliati dalle linee guida nazionali ed internazionali, rende urgente e necessaria la stesura di linee guida locali, così da evitare fallimenti terapeutici futuri. In tal senso, questo studio ha reso disponibile un repertorio di dati epidemiologici locali e attuali che possono sostenere la stesura di tali linee guida: in particolare, prendendo in considerazione gli 87 isolamenti da urinocoltura e/o emocoltura, il 78% si è dimostrato sensibile alla Piperacillina/Tazobactam, che rende questo antibiotico candidato a divenire la prima scelta in terapia empirica in Pronto Soccorso e Medicina Interna dell’Ospedale “F. Lotti” di Pontedera. Il programma di Antimicrobial Stewardship avviato dall’analisi dei risultati precedenti e in via di applicazione nella pratica clinica, prende in esame ogni aspetto della gestione terapeutica del paziente - dal suo ingresso in Pronto Soccorso fino alla dimissione passando attraverso la scelta dell’antibiotico più corretto per la realtà locale - con l’obiettivo di migliorarlo. Questo studio rappresenta pertanto il punto di partenza per ulteriori indagini che potranno analizzare i benefici dell’applicazione nei Reparti di Medicina Interna di questo presidio e potranno facilmente implementarne le raccomandazioni

Three-Dimensional Electro-Anatomical Mapping and Myocardial Work Performance during Spontaneous Rhythm, His Bundle Pacing and Right Ventricular Pacing: The EMPATHY Study

Background. His bundle pacing (HBP) has emerged as an alternative site to right ventricular pacing (RVP) with encouraging outcomes. To date, no study has investigated the systematic approach of three-dimensional electroanatomic mapping (3D-EAM) to guide HBP implantation and to evaluate myocardial activation timing. Furthermore, studies reporting a comprehensive assessment of the ventricular function, using myocardial work (MW) evaluation are lacking. Objectives. (1) To evaluate the systematic use of the 3D-EAM as a guide to HBP; (2) to assess the electrical and mechanical activations with high-density mapping, comparing spontaneous ventricular activation (SVA), HBP and RVP; (3) to assess the myocardial function through speckle-tracking echocardiography (STE) and MW analysis in SVA, HBP and RVP. Methods. 3D-EAM was performed in consecutive patients undergoing HBP implantation with a low use of fluoroscopy. All patients were systematically evaluated with high-density mapping, MW and STE. Results. Fifteen patients were enrolled, of whom three had an implant failure (20%). RV activation time was not statistically different between SVA and HBP (103 vs. 104 ms, p = 0.969) but was significantly higher in RVP (133 ms, p = 0.011 vs. SVA and p = 0.001 vs HBP). Global constructive work was significantly lower during RVP (1191 mmHg%) than during SVA and HBP (1648 and 1505 mmHg%, p = 0.011 and p = 0.008, respectively) and did not differ between SVA and HBP (p = 0.075). Conclusions. 3D-EAM and MW evaluation showed that HBP was comparable to the physiological SVA in terms of activation time and cardiac performance. Compared to both SVA and HBP, RVP was associated with a worse activation timing and ventricular efficiency

Virtual Reality Hypnosis in the Electrophysiology Lab: When Human Treatments Are Better than Virtual Ones

International audienceAims: Virtual reality hypnosis (VRH) has been used successfully in various clinical settings to decrease anxiety and the sensation of pain. We aimed to investigate the feasibility and safety of VRH in patients undergoing electrophysiology and pacing procedures under conscious sedation. Methods: During a two-month period, VRH support was proposed and accepted by 25 patients undergoing electrophysiological procedures. Data were compared with a control group (n = 61) enrolled during the following three-month period. Both groups underwent the measurement of the duration of intervention, the consumption of analgesics and hypnotics, and their pain and comfort using a validated visual analogue scale (VAS 0−10). Results: The baseline characteristics were comparable in both groups, including age. There were no differences in procedure duration (46 (±29) vs. 56 (±32) min, p = 0.18) or in hypnotic/antalgic consumption (midazolam 1.95 (±1.44) vs. 2.00 (±1.22) mg, p = 0.83; sufentanyl 3.78 (±2.87) vs. 3.58 (±2.48) μg, p = 0.9) between the control and VRH groups. In a multivariate analysis, the use of VRH was independently associated with lower comfort during the procedure assessed by postoperative visual analogue scale (OR 15.00 [95% CI 4.77−47.16], p < 0.01). There was no influence of VRH use on pain or drug consumption. Conclusions: In our experience, compared with VRH, human care is preferable during procedures in electrophysiology lab to improve the comfort of the patient. VRH has no influence on pain or drug consumption

Ticagrelor Increases SIRT1 and HES1 mRNA Levels in Peripheral Blood Cells from Patients with Stable Coronary Artery Disease and Chronic Obstructive Pulmonary Disease

Ticagrelor is a powerful P2Y12inhibitor with pleiotropic effects in the cardiovascularsystem. Consistently, we have reported that in patients with stable coronary artery disease (CAD) andconcomitant chronic obstructive pulmonary disease (COPD) who underwent percutaneous coronaryintervention (PCI), 1-month treatment with ticagrelor was superior in improving biological markersof endothelial function, compared with clopidogrel. The objective of this study was to investigate themechanisms underlying these beneficial effects of ticagrelor by conducting molecular analyses ofRNA isolated from peripheral blood cells of these patients. We determined mRNAs levels of markersof inflammation and oxidative stress, such asRORγt(T helper 17 cells marker),FoxP3(regulatoryT cells marker),NLRP3,ICAM1,SIRT1, Notch ligandsJAG1andDLL4,andHES1, a Notch targetgene. We found that 1-month treatment with ticagrelor, but not clopidogrel, led to increased levels ofSIRT1andHES1mRNAs. In patients treated with ticagrelor or clopidogrel, we observed a negativecorrelation among changes in bothSIRT1andHES1mRNA and serum levels of Epidermal GrowthFactor (EGF), a marker of endothelial dysfunction found to be reduced by ticagrelor treatment inour previous study. In conclusion, we report that in stable CAD/COPD patients ticagrelor positivelyregulatesHES1andSIRT1, two genes playing a protective role in the context of inflammation andoxidative stress. Our observations confirm and expand previous studies showing that the beneficialeffects of ticagrelor in stable CAD/COPD patients may be, at least in part, mediated by its capacity toreduce systemic inflammation and oxidative stres

Beta Blockers Improve Prognosis When Used Early in Patients with Cardiogenic Shock: An Analysis of the FRENSHOCK Multicenter Prospective Registry

International audienceBackground: Beta blockers (BBs) are a cornerstone for patients with heart failure (HF) and ventricular dysfunction. However, their use in patients recovering from a cardiogenic shock (CS) remains a bone of contention, especially regarding whether and when to reintroduce this class of drugs. Methods: FRENSHOCK is a prospective multicenter registry including 772 CS patients from 49 centers. Our aim was to compare outcomes (1-month and 1-year all-cause mortality) between CS patients taking and those not taking BBs in three scenarios: (1) at 24 h after CS; (2) patients who did or did not discontinue BBs within 24 h; and (3) patients who did or did not undergo the early introduction of BBs. Results: Among the 693 CS included, at 24 h after the CS event, 95 patients (13.7%) were taking BB, while 598 (86.3%) were not. Between the groups, there were no differences in terms of major comorbidities or initial CS triggers. Patients receiving BBs at 24 h presented a trend toward reduced all-cause mortality both at 1 month (aHR = 0.61, 95% CI 0.34 to 1.1, p = 0.10) and 1 year, which was, in both cases, not significant. Compared with patients who discontinued BBs at 24 h, patients who did not discontinue BBs showed lower 1-month mortality (aHR = 0.43, 95% CI 0.2 to 0.92, p = 0.03) and a trend to lower 1-year mortality. No reduction in outcomes was observed in patients who underwent an early introduction of BB therapy. Conclusions: BBs are drugs of first choice in patients with HF and should also be considered early in patients with CS. In contrast, the discontinuation of BB therapy resulted in increased 1-month all-cause mortality and a trend toward increased 1-year all-cause mortality

Sacubitril/valsartan has an underestimated impact on the right ventricle in patients with sleep-disordered breathing, especially central sleep apnoea syndrome

International audienceBackground: Sacubitril/valsartan has been demonstrated to significantly improve left ventricular performance and remodelling in patients with heart failure. However, its effects on the right ventricle in patients with chronic heart failure and sleep-disordered breathing (SDB) have not been studied.Aim: To investigate the impact of sacubitril/valsartan treatment on right ventricular function in patients with SDB.Methods: This was a subanalysis of an observational prospective multicentre study involving 101 patients. At inclusion, patients were evaluated by echocardiography and nocturnal ventilatory polygraphy, which allowed patients to be divided into three groups: “central-SDB‿; “obstructive-SDB‿; and “no-SDB‿.Results: After 3 months of sacubitril/valsartan therapy, a positive impact on right ventricular function was observed. In the general population, tricuspid annular plane systolic excursion increased by +1.32 ± 4.74 mm (P = 0.024) and systolic pulmonary artery pressure decreased by –3.1 ± 10.91 mmHg (P = 0.048). The central-SDB group experienced the greatest echocardiographic improvement, with a significant increase in tricuspid annular plane systolic excursion of +2.1 ± 4.9 mm (P = 0.045) and a significant reduction in systolic pulmonary artery pressure of –8.4 ± 9.7 mmHg (P = 0.001).Conclusions: Sacubitril/valsartan improved right ventricular function in patients with heart failure and SDB after only 3 months of treatment. The greatest improvement in right ventricular function was observed in the central-SDB group