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MODULAZIONE DELLA RISPOSTA INFIAMMATORIA NELLA PREVENZIONE DELLA RESTENOSI POST STENT CORONARICO: IL TRIAL CLINICO MULTICENTRICO RANDOMIZZATO “CEREA-DES”
Full text linkObiettivo: è conosciuto che l’aterosclerosi coronarica e la restenosi intra-stent sono processi in gran parte regolari da meccanismi infiammatori sistemici. Questo studio ha arruolato pazienti con coronarosclerosi significativa trattabile con angioplastica coronarica ed impianto di stent. Lo scopo dello studio è la comparazione dei risultati clinici ottenuti in un gruppo di controllo trattato con impianto di stent metallici (BMS) con due gruppi in trattamento: impianto di BMS e terapia orale con prednisone o impianto di stent a rilascio di farmaco (DES), in presenza di terapia medica ottimale per tutti i gruppi. In un sottogruppo di pazienti si è indagato il rilascio di interleuchina-6 (IL-6), tumor necrosis factor-a (TNF-a) e l’attivazione di NF-kB in monociti circolanti. Si è anche studiata una possibile relazione tra il pattern di attivazione monocitaria e la crescita neointimale che segue l’impianto di uno stent metallico.
Metodi: in 5 centri ospedalieri italiani di alta specializzazione sono stati arruolati 375 pazienti non diabetici con patologia coronarica, senza controindicazioni ad eseguire doppia terapia antiaggregante o terapia corticosteroidea, nel contesto di uno studio clinico randomizzato, controllato ed indipendente, condotto tra il 2007 ed il 2009. I pazienti sono stati allocati in tre gruppi da 125 soggetti ciascuno: BMS (gruppo di controllo), BMS e trattamento orale con alte dosi di prednisone a scalare per 40 giorni (gruppo BMS+prednisone) oppure stent medicato (gruppo DES). L’end-point primario era rappresentato dalla sopravvivenza libera da morte cardiovascolare, infarto miocardico, e ricorrenza di ischemia con necessità di nuova rivascolarizzazione sul vaso responsabile ad un anno di follow-up. Gli eventi clinici sono stati assegnati da un comitato indipendente preposto all’incarico. Inoltre, 40 pazienti sono entrati a far parte del sottostudio volto ad esaminare il pattern di attivazione monocitaria (20 pazienti dal gruppo BMS e 20 pazienti da gruppo BMS+Prednisone). In questo gruppo è stato dosato il rilascio di IL-6, TNF-a e l’attivazione di NF-kB da monociti periferici non stimolati e stimolati con LPS o PMA, al basale e dopo 10 e 30 giorni dalla procedura. Il Late Lumen Loss (LLL) al controllo angiografico (in media 9 mesi dalla procedura indice) è stato calcolato attraverso l’analisi coronarica quantitativa (QCA).
Risultati: è stato raccolto il follow-up a 12 mesi per tutti i pazienti arruolati. I pazienti del gruppo di controllo (BMS) hanno mostrato una sopravvivenza libera da eventi cardiaci minore rispetto a quella dei pazienti trattati con DES o BMS+Prednisone. L’end-point primario era dell’80.8% nel gruppo BMS, dell’88.0% nel gruppo BMS+Prednisone e dell’88.8% nel gruppo DES (rispettivamente p=0.04 e p=0.006 rispetto ai controlli). I benefici della terapia steroidea apparivano concentrati in quei pazienti con infiammazione attivata, in cui si riscontrava quindi una proteina C reattiva ad alta sensibilità (hs-PCR) elevata. La terapia con prednisone utilizzata nello studio si è dimostrata ben tollerabile, essendo gli effetti collaterali riscontrati in genere di lieve entità e reversibili (soprattutto edemi e ritenzione idrica). Le concentrazioni plasmatiche di prednisone correlavano inversamente con il rilascio monocitario di IL-e TNF-a (rispettivamente R2 = 0.45,p = 0.04 and R2 = 0.69, p = 0.005) e con l’attivazione di NF-kB (R2 = 0.58, p = 0.01). La riduzione del rilascio di TNF-a e l’attivazione di NF-kB risultavano significativamente correlate (R2 = 0.56, p = 0.01). I pazienti in terapia con prednisone mostravano una riduzione del rilascio di citochine proinfiammatorie e dell’attivazione di TNF-a a 10 e 30 giorni significativamente maggiori rispetto ai soggetti non trattati. I valori di LLL al follow-up angiografico risultavano significativamente minori nel gruppo prednisone (0.44±0.35mm vs 0.80±0.53mm, p = 0.02) e correlavano con la riduzione del rilascio di TNF-a (R2 = 0.41,p = 0.01).
Conclusioni: Il trattamento con DES o BMS+Prednisone, rispetto all’impianto del solo BMS, si accompagna ad una maggiore sopravvivenza libera da eventi cardiaci ad un anno dalla procedura. Si confermano precedenti esperienze di ricerca che indicano i pazienti con infiammazione attivata (elevata hs-PCR) come coloro che maggiormente possono beneficiare della terapia steroidea. La terapia steoidea a dosaggio immunosoppressivo, somministrata per via orale in un limitato periodo di tempo (40 giorni) è efficace nel ridurre l’attivazione monocitaria mediata dalla via del fattore trascrizionale NF-kB ed il conseguente rilascio di citochine pro-infiammatorie in pazienti trattati con stenting coronarico. La riduzione del rilascio di TNF-a correla con la riduzione di LLL al follow-up angiografico, confermando così il razionele del potenziale beneficio della terapia con prednisone nella prevenzione della restenosi intra-stent.Objective: it is known that coronary atherosclerosis and in-stent restenosis are largely ruled by inflammatory mechanisms. This study enrolled patients with coronary artery disease amenable to percutaneous coronary interventions and stent implantation. Its aim was to compare the clinical outcome obtained in a control group of patients treated with bare metal stent (BMS) versus other two study groups: BMS plus oral prednisone or drug eluting stents (DES), all assuming similar optimal adjunctive medical treatment. In a subgroup of patients the release of interleukin-6 (IL-6), tumour necrosis factor (TNF-a) and NF-kB activation in circulating monocytes were studied and also related with the neointimal growth that follows bare metal stent (BMS) implantation.
Methods: five tertiary Italian hospitals enrolled 375 non-diabetic patients with coronary artery disease and no contraindications to dual anti-platelet treatment or corticosteroid therapy in a randomized, controlled, independent study performed between 2007 and 2009. Patients were allocated into three study groups of 125 patients each: BMS (controlgroup), BMS followed by a 40-day prednisone treatment (BMS and prednisone group) or DES (DES group). Primary endpoint was the event-free survival of cardiovascular death, myocardial infarction and recurrence of ischemia needing repeated target vessel revascularization at one year as adjudicated by an independent clinical events committee. Moreover, 40 patients (20 from the control group and 20 from the Prednisone group) entered the monocyte activation sub-study. The release of IL-6, TNF-a and NF-kB p50 subunit translocation at baseline, at 10 and 30 days were evaluated from peripheral non-stimulated and stimulated (LPS and PMA) monocytes. Late luminal loss (LLL) 9 months after angioplasty was calculated by quantitative coronary angiography.
Results: one-year follow-up was obtained in all patients. Patients receiving BMS alone as compared to those treated with prednisone or DES had lower event-free survival; the primary endpoint was 80.8% in controls compared to 88.0% in the BMS and prednisone and 88.8% in the DES groups respectively (p=0.04 and p=0.006). The benefits of the steroids appear to be restricted to patients with an activated inflammation, identified by an elevated hs-PCR. Prednisone therapy resulted well tolerated and generally associated with mild and reversible side effects. Plasma concentrations of prednisone correlated inversely with IL-6 and TNF-a release (R2 = 0.45,p = 0.04 and R2 = 0.69, p = 0.005, respectively) and NF-kB activation from monocytes (R2 = 0.58, p = 0.01). The reduction of TNF-a release and NF-kB activation were significantly related (R2 = 0.56, p = 0.01). Prednisone patients showed a significantly larger reduction of cytokine release and NF-kB activation compared to non-treated patients, at 10 days and 30 days. LLL was lower in the prednisone group (0.44±0.35mm versus 0.80±0.53mm, p = 0.02) and correlated with reduction of TNF-a (R2 = 0.41,p = 0.01).
Conclusions: as compared with BMS alone, prednisone treatment after BMS or DES implantation result in a better event-free survival at one year. Previous observations on the benefits of the steriods in patients with active inflammation (elevated hs-PCR) are confirmed. High doses of oral prednisone reduce NF-kB pathway activation and pro-inflammatory cytokine release in circulating activated monocytes of patients treated with coronary stenting. TNF-a release reduction correlates with decreased LLL, confirming a potential benefit of steroid therapy in preventing in-stent restenosis
The promise of vascular reparative therapy in standby mode. How long before a final decision? Complete vessel wall regeneration and vascular scaffold resorption after left anterior descending reconstructions
No full textThe promise of vascular reparative therapy in standby mode. How long before a final decision? Complete vessel wall regeneration and vascular scaffold resorption after left anterior descending reconstructions
Current Antithrombotic Therapy in Patients with Acute Coronary Syndromes Undergoing Percutaneous Coronary Interventions
No full text: Acute coronary syndromes (ACS) represent a life-threatening complication of the systemic atherosclerotic process, affecting the coronary circulation. Thrombosis, defined as an uncontrolled activation of the endogenous thrombogenetic reparative process, often follows atherosclerotic plaque damage and is mainly engaged by two main pathways: platelet aggregation and coagulation. Therefore, antithrombotic therapy to modulate either pathway plays an important role for the reduction of ischaemic adverse events in ACS patients. Since the advent of aspirin and warfarin, numerous antiaggregant and anticoagulant molecules have been developed to achieve this goal, but their anti-ischaemic efficacy is often obtained at the price of augmented bleedings, which are known to be strong predictors of adverse outcome. This article briefly reviews the physiopathological mechanisms of thrombosis and presents an overview of the available literature supporting the use of these major drugs, as well as the European Society of Cardiology recommendations for their utilisation in the setting of non-ST and ST-elevation myocardial infarction undergoing invasive treatment
Osteomyelitis of the clavicle following to a pacemaker implantation
No full textOsteomyelitis of the clavicle following to a pacemaker implantation
Transcatheter edge-to-edge mitral valve repair: what is the measure of success?
No full textTranscatheter edge-to-edge mitral valve repair: what is the measure of success
Devices for mechanical circulatory support and strategies for their management in cardiogenic shock
Full text linkCardiogenic shock (CS) is a low cardiac output state resulting in end-organ hypoperfusion and hypoxia, which, if untreated, leads to an irreversible multiorgan failure. Acute coronary syndrome is the most common cause of CS, with a high prevalence of patients with multivessel disease. Cardiogenic shock management remains a challenge, since mortality rates are still high and have not declined over the last 20 years. The treatment strategy of CS in patients with acute coronary syndrome needs to take into account both the presence of myocardial ischemia and tissue hypoperfusion. The first part of this review focuses on the characteristics, hemodynamic profile, and available evidence of the mechanical circulatory support devices for an optimal patient-device matching. The second part focuses on the management strategy of CS in terms of myocardial revascularization and hemodynamic support in light of the most recent available evidence
Significant Drop in Right Atrial Pressure Does Not Influence Fractional Flow Reserve Coronary Assessment
No full textThe effect of a highly elevated level of right atrial filling pressure on fractional flow reserve (FFR) measurement remains unclear. Transcatheter tricuspid valve intervention, a recently introduced option for inoperable or high-risk patients, represents a unique model of in-vivo physiology to investigate the eventual influence of central venous pressure on coronary FFR measurements. The case is reported of a patient with a degenerated tricuspid surgical bioprosthesis who underwent transcatheter tricuspid valve-in-valve replacement and concomitant coronary functional assessment with FFR. In an experimental model, the significant fall in right atrial pressure did not influence FFR measurements in the presence of angiographically proven mild coronary artery disease
"Valve in valve" implantation of two self-expandable transcatheter aortic valves in a patient with aortic root aneurysm and massive aortic regurgitation: "a new TAVI option"
No full textCatheter-based treatment of aortic regurgitation (AR) often proves challenging especially due to associated anatomical difficulties. Here, we present a case of CoreValve implantation with a novel use of the valve-in-valve technique to effectively treat severe AR in a patient with repeated cardiac surgery and aneurismatic prosthetic ascending aorta
Choosing transcatheter aortic valve replacement in porcelain aorta: outcomes versus surgical replacement
No full textcommentary on choosing transcatheter aortic valve replacement in porcelain aort
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