Heart rate reduction with esmolol is associated with improved arterial elastance in patients with septic shock: a prospective observational study.

PURPOSE: Ventricular-arterial (V-A) decoupling decreases myocardial efficiency and is exacerbated by tachycardia that increases static arterial elastance (Ea). We thus investigated the effects of heart rate (HR) reduction on Ea in septic shock patients using the beta-blocker esmolol. We hypothesized that esmolol improves Ea by positively affecting the tone of arterial vessels and their responsiveness to HR-related changes in stroke volume (SV). METHODS: After at least 24 h of hemodynamic optimization, 45 septic shock patients, with an HR ≥95 bpm and requiring norepinephrine to maintain mean arterial pressure (MAP) ≥65 mmHg, received a titrated esmolol infusion to maintain HR between 80 and 94 bpm. Ea was calculated as MAP/SV. All measurements, including data from right heart catheterization, echocardiography, arterial waveform analysis, and norepinephrine requirements, were obtained at baseline and at 4 h after commencing esmolol. RESULTS: Esmolol reduced HR in all patients and this was associated with a decrease in Ea (2.19 ± 0.77 vs. 1.72 ± 0.52 mmHg l(-1)), arterial dP/dt max (1.08 ± 0.32 vs. 0.89 ± 0.29 mmHg ms(-1)), and a parallel increase in SV (48 ± 14 vs. 59 ± 18 ml), all p < 0.05. Cardiac output and ejection fraction remained unchanged, whereas norepinephrine requirements were reduced (0.7 ± 0.7 to 0.58 ± 0.5 µg kg(-1) min(-1), p < 0.05). CONCLUSIONS: HR reduction with esmolol effectively improved Ea while allowing adequate systemic perfusion in patients with severe septic shock who remained tachycardic despite standard volume resuscitation. As Ea is a major determinant of V-A coupling, its reduction may contribute to improving cardiovascular efficiency in septic shock.

The Effect of inotropes and vasopressors on mortality: a meta-analysis of randomized clinical trials.

BACKGROUND: Inotropes and vasopressors are frequently administered to critically ill patients in order to improve haemodynamic function and restore adequate organ perfusion. However, some studies have suggested a possible association between inotrope administration and increased mortality. We therefore performed a meta-analysis of randomized trials published in the last 20 yr to investigate the effect of these drugs on mortality. METHODS: BioMedCentral, PubMed, Embase and the Cochrane Central Register were searched (all updated April 8th, 2015). Inclusion criteria were: random allocation to treatment, at least one group receiving an inotropic or vasopressor drug compared with at least one group receiving a non-inotropic/vasopressor treatment, study published after 1st January 1994, and systemic drug administration. Exclusion criteria were overlapping populations, studies published as abstract only, crossover studies, paediatric studies and lack of data on mortality. RESULTS: A total of 28 280 patients from 177 trials were included. Overall, pooled estimates showed no difference in mortality between the group receiving inotropes/vasopressors and the control group [4255/14 036 (31.7%) vs. 4277/14 244 (31.8%), risk ratio=0.98 (0.96-1.01), P for effect=0.23, P for heterogeneity=0.30, I2=6%]. A reduction in mortality was associated with inotrope/vasopressor therapy use in settings of vasoplegic syndromes, sepsis and cardiac surgery. Levosimendan was the only drug associated with improvement in survival. Subgroup analysis did not identify any groups with increased mortality associated with inotrope/vasopressor therapy. CONCLUSIONS: Our systematic review found that inotrope/vasopressor therapy is not associated with differences in mortality in the overall population and in the majority of subsettings.

Risk of pocket hematoma in patients on chronic anticoagulation with warfarin undergoing electrophysiological device implantation: a comparison of different peri-operative management strategies.

OBJECTIVE: Periprocedural management of warfarin remains challenging in patients requiring electrophysiological device surgery. For patients at high risk of thromboembolic events, guidelines recommend bridging therapy with heparin; however, this strategy is associated with a high risk of pocket hematoma. This paper systematically reviews studies appraising the risk of pocket hematoma with different perioperative anticoagulation strategies. METHODS: All relevant studies identified in MEDLINE/PubMed, The Cochrane Collaboration CENTRAL, clinicaltrials.org and in bibliographies of key articles. Estimates were combined using a fixed effects model. Heterogeneity was assessed by p values of χ2 statistics and I2. Publication bias was assessed by visual examination of funnel plots and by Egger test. Fifteen studies enrolling 5911 patients met all inclusion criteria and were included in this review. RESULTS: Heparin bridging compared with no heparin was associated with increased risk of pocket hematoma (OR = 4.47, 95% CI 3.21-6.23, p < 0.00001), and prolonged hospital stay (9.13 ± 1.9 days vs. 5.11 ± 1 .39 days, p < 0.00001). Warfarin continuation was not associated with increased pocket hematoma compared to warfarin discontinuation (p = 0.38), but was associated with reduced risk of pocket hematoma compared with heparin bridging (OR = 0.37, 95% CI 0.2-0.69, p = 0.002). Thromboembolic complications were reduced with heparin bridging vs. no heparin (0.50% vs.1.07%, p = 0.02), and no significant differences were reported between heparin bridging vs. warfarin continuation (p = 0.83). CONCLUSIONS: Heparin bridging is associated with a higher risk of pocket hematoma and a prolonged hospital stay. Perioperative continuation of warfarin reduces the occurrence of pocket hematoma compared with heparin bridging without any significant differences in thromboembolic complications.

Network meta-analysis on the comparative effectiveness and safety of transcatheter aortic valve implantation with CoreValve or Sapien devices versus surgical replacement.

INTRODUCTION: Surgical replacement for aortic stenosis is fraught with complications in high-risk patients. Transcatheter techniques may offer a minimally invasive solution, but their comparative effectiveness and safety is uncertain. We performed a network meta-analysis on this topic. METHODS: Randomized trials on transcatheter aortic valve replacement vs surgery were searched. The primary outcome was all cause death. Risk estimates were obtained with Bayesian network meta-analytic methods. RESULTS: Four trials with 1,805 patients were included. After a median of 8 months, risk of death and myocardial infarction was not different when comparing surgery versus transcatheter procedures, irrespective of device or access. Conversely, surgery was associated with higher rates of major bleeding (odds ratio vs CoreValve=3.03 [95% credible interval: 2.23-4.17]; odds ratio vs transfemoral Sapien =1.82 [1.21-2.70]; odds ratio vs transapical Sapien =2.08 [1.20-3.70]), and acute kidney injury (odds ratio vs CoreValve =2.08 [1.33-3.32]; odds ratio vs transapical Sapien =2.78 [2.21-99.80]), but lower rates of pacemaker implantation (odds ratio vs CoreValve =0.41 [0.28-0.59]), and moderate or severe aortic regurgitation (odds ratio vs CoreValve =0.06 [0.02-0.27]; odds ratio vs Sapien=0.17 [0.02-0.76]). Strokes were less frequent with CoreValve than with transfemoral Sapien (odds ratio =0.32 [0.13-0.73]) or transapical Sapien (odds ratio =0.33 [0.10-0.93]), whereas pacemaker implantation was more common with CoreValve (odds ratio vs surgery =2.46 [1.69-3.61]; odds ratio vs transfemoral Sapien =2.22 [1.27-3.85]). CONCLUSIONS: Survival after transcatheter or surgical aortic valve replacement is similar, but there might be differences in the individual safety and effectiveness profile between the treatment strategies and the individual devices used in transcatheter aortic valve implantation.

Epicatechin and catechin modulate endothelial activation induced by platelets of patients with peripheral artery disease.

Platelet activation contributes to the alteration of endothelial function, a critical initial step in atherogenesis through the production and release of prooxidant mediators. There is uncertainty about the precise role of polyphenols in interaction between platelets and endothelial cells (ECs). We aimed to investigate whether polyphenols are able to reduce endothelial activation induced by activated platelets. First, we compared platelet activation and flow-mediated dilation (FMD) in 10 healthy subjects (HS) and 10 patients with peripheral artery disease (PAD). Then, we evaluated the effect of epicatechin plus catechin on platelet-HUVEC interaction by measuring soluble cell adhesion molecules (CAMs), NOx production, and eNOS phosphorylation (p-eNOS) in HUVEC. Compared to HS, PAD patients had enhanced platelet activation. Conversely, PAD patients had lower FMD than HS. Supernatant of activated platelets from PAD patients induced an increase of sCAMs release and a decrease of p-eNOS and nitric oxide (NO) bioavailability compared to unstimulated HUVEC. Coincubation of HUVEC, with supernatant of PAD platelets patients, pretreated with a scalar dose of the polyphenols, resulted in a decrease of sCAMs release and in an increase of p-eNOS and NO bioavailability. This study demonstrates that epicatechin plus catechin reduces endothelial activation induced by activated platelets.

Appraising failure of surgical and percutaneous revascularization: long term outcomes from an observational registry.

AIM: Many randomized trials have compared coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI) in terms of efficacy, but data comparing outcomes of patients in which these two techniques have failed are lacking. METHODS: We included patients undergoing PCI at our center between July 2002 and December 2004. Subjects were distinguished in 2 groups: those with at least one occluded or stenotic saphenous vein graft (CABG failure), and those with at least one stent with angiographically documented restenosis (PCI failure). The primary endpoint was the long-term rate of major adverse clinical events. RESULTS: Two hundred and thirthy four patients were included, with a medium follow up of 61±13 months; 134 were assigned to the CABG failure group, and 104 to the PCI failure group, sharing high rates of baseline risk factors. At long term rates of death were higher in post CABG group (22.1% vs. 9.9%; P=0.015, RR 2.24 C.I. 95% 1.14-4.40) while death rates in patients with diagnosis of diabetes mellitus (24.0% vs. 23.5%; P=0.969, RR 1.020 C.I. 95% 0.38-2.74) were not different CONCLUSION: PCI can be safely offered to both these kinds of patients: as recently demonstrated post CABG outcomes seem to be more favorable in patients with diabetes mellitus.

Anaesthetic drugs and survival: a Bayesian network meta-analysis of randomized trials in cardiac surgery.

BACKGROUND: Many studies have compared desflurane, isoflurane, sevoflurane, total i.v. anaesthesia (TIVA), or all in cardiac surgery to assess their effects on patient survival. METHODS: We performed standard pairwise and Bayesian network meta-analyses; the latter allows indirect assessments if any of the anaesthetic agents were not compared in head-to-head trials. Pertinent studies were identified using BioMedCentral, MEDLINE/PubMed, Embase, and the Cochrane Library (last updated in June 2012). RESULTS: We identified 38 randomized trials with survival data published between 1991 and 2012, with most studies (63%) done in coronary artery bypass grafting (CABG) patients with standard cardiopulmonary bypass. Standard meta-analysis showed that the use of a volatile agent was associated with a reduction in mortality when compared with TIVA at the longest follow-up available [25/1994 (1.3%) in the volatile group vs 43/1648 (2.6%) in the TIVA arm, odds ratio (OR)=0.51, 95% confidence interval (CI) 0.33-0.81, P-value for effect=0.004, number needed to treat 74, I(2)=0%] with results confirmed in trials with low risk of bias, in large trials, and when including only CABG studies. Bayesian network meta-analysis showed that sevoflurane (OR=0.31, 95% credible interval 0.14-0.64) and desflurane (OR=0.43, 95% credible interval 0.21-0.82) were individually associated with a reduction in mortality when compared with TIVA. CONCLUSIONS: Anaesthesia with volatile agents appears to reduce mortality after cardiac surgery when compared with TIVA, especially when sevoflurane or desflurane is used. A large, multicentre trial is warranted to confirm that long-term survival is significantly affected by the choice of anaesthetic.

Circulating tumor cells in metastatic colorectal cancer: do we need an alternative cutoff?

PURPOSE: To assess the prognostic and predictive value of circulating tumor cells (CTCs) in metastatic colorectal cancer (mCRC) irrespective of detection level. MATERIALS AND METHODS: We evaluated the prognostic and predictive significance of CTC count at baseline and under treatment in 119 mCRC subjects and compared the standard cutoff (≥3 CTCs/7.5 mL to ≥1 CTCs/7.5 mL). RESULTS: An overall comparison was made between patients with 0, 1-2 and ≥3 CTC (median PFS 8, 4 and 5 months, respectively). Two poor prognostic groups were found, including patients with ≥1 CTCs before and during treatment and patients with 0 CTC at baseline who converted to ≥1 CTCs (p = 0.014). CONCLUSIONS: The presence of at least 1 CTC at baseline count is predictive for poor prognosis in mCRC patients. Patients with 1-2 CTC should be switched from the favorable prognostic group--conventionally defined by the presence of <3 CTC--to the unfavorable, deserving a more careful monitoring.

Very long-term outcome of peripheral arterial disease in patients undergoing percutaneous coronary revascularization: a retrospective analysis.

AIM: Peripheral arterial disease (PAD) in patients undergoing percutaneous coronary intervention (PCI) with stent implantation is a well known risk factor leading to an increased rates of stroke, cardiovascular death and myocardial infarction. Anyway there are few data on very-long term outcome (more than 1 year follow up) of PAD after stent implantation. We thus aimed to evaluate the influence of PAD on very long-term outcome of our PCI-population. METHODS: We retrospectively identified all patients undergoing PCI with stent implantation at our center between July 2002 and June 2004, and thus eligible for at least 4 years of follow-up. For the purpose of this study, we considered a diagnosis of PAD based on clinical evaluation and/or angiographic documentation. We adjudicated the following clinical events: death, myocardial infarction, repeat revascularization, and their composite (i.e. major adverse cardiac events, MACE). RESULTS; A total of 1008 patients were included, 109 with PAD and 899 Without PAD. Those with had more often diabetes (35% vs. 25%, P=0.002), hypertension (83% vs. 68%, P=0.001) and unfavorable basal clinical condition at the start of this study: past-Percutaneous Coronary Intervention (PCI) (30% vs. 22%, P=0.005), past-Coronary Artery Bypass Graft (CABG) (24% vs. 14%, P=0.001), ejection fraction (EF) <35% (14% vs. 7%, P=0.02) and chronic renal failure (CRF) (15% vs. 6%, P=0.002). In addiction patient with PAD were more likely to have chronic total occlusion (CTO) (36% vs. 25%, p=0.02) and unprotected left main (16% vs. 8%,P=0.01). Clinical outcome at the time of follow-up (4,42 ± 1,66 years) was as follow: Revascularization (53% vs. 37%, P=0.002), Cardiac death (21% vs. 13%, P=0.04), MACE (69% vs. 49%, p<.001). Independent predictors of MACE according to our survival analysis were: PAD (HR 1.31; 95% CI 1.01-1.69), Age >75 (HR 1.23; 95% CI 1-1.51), Chronic heart failure (HR1.72; 95% CI 1.19-2.5), Unprotected left main (HR 1.48; 95% CI 1.12-1.96). CONCLUSION: This long-term registry shows that PAD remains an important clinical condition that negatively influences the outcome of patients undergoing PCI with stent implantation in a very long-term follow-up period.

Advances in below-the-knee drug-eluting balloons.

The management of critical limb ischemia due to below-the-knee disease remains challenging due to the frequent patient comorbidities, diffuse vascular involvement, and high rates of restenosis and disease progression. The BASIL study has established the substantial equivalence between bypass surgery and percutaneous transluminal angioplasty in this setting, at least at mid-term follow-up, but percutaneous techniques and devices have seen major developments since the publication of this pivotal trial in 2005. A major breakthrough has indeed been the introduction of drug-eluting balloons, which have several theoretical advantages in comparison to standard balloons and metallic stents for infra-popliteal lesions. Two clinical trials have already been reported with favorable results for the In.Pact Amphirion paclitaxel-eluting balloon, when employed for below-the-knee lesions. We hereby discuss the rationale for the use of drug-eluting balloons in this complex setting and the main findings of the study by Schmidt et al. and the DEBATE-BTK trial.

Mortality reduction in cardiac anesthesia and intensive care: results of the first International Consensus Conference.

There is no consensus on which drugs/techniques/strategies can affect mortality in the perioperative period of cardiac surgery. With the aim of identifying these measures, and suggesting measures for prioritized future investigation we performed the first International Consensus Conference on this topic. The consensus was a continuous international internet-based process with a final meeting on 28 June 2010 in Milan at the Vita-Salute University. Participants included 340 cardiac anesthesiologists, cardiac surgeons, and cardiologists from 65 countries all over the world. A comprehensive literature review was performed to identify topics that subsequently generated position statements for discussion, voting, and ranking. Of the 17 major topics with a documented mortality effect, seven were subsequently excluded after further evaluation due to concerns about clinical applicability and/or study methodology. The following topics are documented as reducing mortality: administration of insulin, levosimendan, volatile anesthetics, statins, chronic ß-blockade, early aspirin therapy, the use of pre-operative intra-aortic balloon counterpulsation, and referral to high-volume centers. The following are documented as increasing mortality: administration of aprotinin and aged red blood cell transfusion. These interventions were classified according to the level of evidence and effect on mortality and a position statement was generated. This International Consensus Conference has identified the non-surgical interventions that merit urgent study to achieve further reductions in mortality after cardiac surgery: insulin, intra-aortic balloon counterpulsation, levosimendan, volatile anesthetics, statins, chronic ß-blockade, early aspirin therapy, and referral to high-volume centers. The use of aprotinin and aged red blood cells may result in increased mortality.

Mortality reduction in cardiac anesthesia and intensive care: results of the first International Consensus Conference.

BACKGROUND: There is no consensus on which drugs/techniques/strategies can affect mortality in the perioperative period of cardiac surgery. With the aim of identifying these measures, and suggesting measures for prioritized future investigation we performed the first international consensus conference on this topic. METHODS: The consensus was a continuous international internet-based process with a final meeting on June 28th 2010 in Milan at the Vita-Salute University. Participants included 340 cardiac anesthesiologists, cardiac surgeons and cardiologists from 65 countries all over the world. A comprehensive literature review was performed to identify topics that subsequently generated position statements for discussion, voting and ranking. RESULTS: Of the 17 major topics with a documented mortality effect, seven were subsequently excluded after further evaluation due to concerns about clinical applicability and/or study methodology. The following topics are documented as reducing mortality: administration of insulin, levosimendan, volatile anesthetics, statins, chronic beta-blockade, early aspirin therapy, the use of preoperative intra-aortic balloon counterpulsation and referral to high-volume centers. The following are documented as increasing mortality: administration of aprotinin and aged red blood cell transfusion. These interventions were classified according to the level of evidence and effect on mortality and a position statement was generated. CONCLUSION: This international consensus conference has identified the non-surgical interventions that merit urgent study to achieve further reductions in mortality after cardiac surgery: insulin, intra-aortic balloon counterpulsation, levosimendan, volatile anesthetics, statins, chronic beta-blockade, early aspirin therapy, and referral to high-volume centers. The use of aprotinin and aged red blood cells may result in increased mortality.

Current concepts on antiplatelet therapy: focus on the novel thienopyridine and non-thienopyridine agents.

Thienopyridines are a class of drug targeting the platelet adenosine diphosphate (ADP) 2 receptor. They significantly reduce platelet activity and are therefore clinically beneficial in settings where platelet activation is a key pathophysiological feature, particularly myocardial infarction. Ticlopidine, the first of the class introduced to clinical practice, was soon challenged and almost completely replaced by clopidogrel for its better tolerability. More recently, prasugrel and ticagrelor have been shown to provide a more powerful antiplatelet action compared to clopidogrel but at a cost of higher risk of bleeding complications. Cangrelor, a molecule very similar to ticagrelor, is currently being evaluated against clopidogrel. Considering the key balance of ischemic protection and bleeding risk, this paper discusses the background to the development of prasugrel, ticagrelor, and cangrelor and aims to characterise their risk-benefit profile and possible implementation in daily practice.

Short and long-term outcomes of percutaneous revascularization in patients with prior coronary artery bypass graft.

AIM: Patients with prior coronary artery bypass grafting (CABG) represent a sizable portion of those undergoing percutaneous coronary intervention (PCI): in many instances, it is unclear whether performing PCI on the bypass graft or in the native coronary vessels can offer the best risk-benefit balance. METHODS: We included patients with prior CABG undergoing PCI at our center between July 2002 and June 2004 and we distinguished them in three groups. Those in whom PCI was performed on stenotic saphenous vein graft (SVG group), those in whom PCI was performed on native vessels despite the presence of potentially treatable SVG disease (optional native group), and those in whom PCI had to be performed mandatorily in the native vessels because of chronic SVG occlusions or disease in non-bypassed segments (mandatory native group). The primary end-point was long-term rate of major adverse clinical events (MACE, i.e. death, myocardial infarction, or target vessel revascularization). RESULTS: We identified 109 patients: 28 were in the SVG group, 25 in the optional native group, and 56 in the mandatory native group. Early major adverse cardiac events (MACE) occurred with similar frequency in the three groups (respectively, 9.1%, 0% and 5.7%, P=0.35). After more than three years of follow-up, MACE occurred in 39.3% vs. 28 and 39.4% (P=0.59), death occurred in 27.2 vs. 24.0% vs. 13.5% (P=0.30), and TVR in 27.3% vs. 8.0% vs. 28.8% (P=0.14). CONCLUSION: In selected patients, PCI of native coronary vessels despite the presence of apparently treatable SVG lesions can be envisioned.

What is the risk of intensifying platelet inhibition beyond clopidogrel? A systematic review and a critical appraisal of the role of prasugrel.

Thienopyridines are a class of drug targeting the platelet adenosine diphosphate 2 receptor. They have been shown to significantly reduce platelet activity exerting an important role in those clinical settings in which such an effect is beneficial. Ticlopidine was first to be introduced several years ago but it was quickly replaced by clopidogrel as it had a better risk/benefit profile. Recently, prasugrel has been developed and tested in several ex vivo studies and clinical trials showing able to provide a more powerful antiplatelet effect at the expense of a higher risk of bleeding complications. Great debate rose around its recent approval in the US as well as in Europe. This review aims at exploring the development and available clinical data of this third-generation thienopyridine while discussing its practical implementation in routine practice.

Myocardial infarction after percutaneous coronary intervention: a meta-analysis of troponin elevation applying the new universal definition.

AIM: Elevation of Troponin after scheduled percutaneous coronary intervention (PCI) is a recognized consequence. We sought to evaluate the prognostic significance and impact of the newly published definition of PCI-related myocardial infarction (MI) according to which any troponin elevation >3 times the upper reference limit identify a peri-procedural MI. METHODS: Search of BioMedCentral, CENTRAL, mRCT and PubMed (updated May 2008). Outcomes of interest were: MACE [the composite of all cause death, MI, repeat target vessel PCI (re-PCI) and coronary artery bypass grafting (CABG)]; single end points were also assessed. RESULTS: Fifteen studies have been included totalling 7578 patients. Troponin elevation occurred in 28.7% of the procedures. The incidence of PCI-related MI according to the new definition was 14.5%. During the hospitalization, any level of raised troponin was associated with an increased risk of MACE [OR 11.29 (3.00-42.48), Number needed to harm (NNH) 5], death [OR 7.16 (1.95-26.27), NNH = 100], MI [OR 30.85 (6.05-157.38), NNH = 4] and re-PCI [OR 4.13 (1.23-13.88), NNH = 50]. Patients with PCI-related MI had an increased risk of death [OR 17.25 (2.71-109.96), NNH = 100] and re-PCI [OR 10.86 (3.2-36.94), NNH = 25]. At follow up of 18 months any troponin elevation was associated with an increased risk of MACE [OR 1.48 (1.12-1.96), NNH = 20], death [OR 2.19 (1.59-3.00), NNH = 50], MI [OR 3.29 (2.71-6.31), NNH = 33] and re-PCI [OR 1.47 (1.06-2.03), NNH = 25]. In patients with PCI-related MI the risk of MACE was further increased: OR 2.25 (1.26-4.00), NNH = 3. An increase of the troponin level below the cut-off was not associated with MACE. CONCLUSION: A diagnosis of MI according to the new guidelines applies to 15% of patients undergoing PCI and these patients are at high risk of further adverse events both during the hospital stay and at 18 months.

Percutaneous aortic valve replacement in two cases at high surgical risk: procedural details and implications for patient selection.

The morbidity and mortality burden of heart valve disease is increasing in the developing world, especially among the elderly. Whereas surgery remains the standard of care in fit patients with degenerative aortic stenosis, percutaneous aortic valve replacement could become an effective alternative to surgery in selected higher risk patients. The authors report on two women with aortic stenosis, both at high surgical risk (an 81-year-old female with coronary artery and cerebro-vascular disease, and a 70-year-old female with end-stage cirrhosis), in whom percutaneous valve replacement was effectively performed by means of transfemoral access and retrograde CoreValve Re-valving System implantation. Two major post-procedural complications occurred, both effectively managed, in the second patient: a third degree atrio-ventricular block (requiring permanent pace-maker implantation) and bleeding from the right femoral artery access (requiring implantation of two covered stents and blood transfusion). Despite the increased baseline risk, both patients were discharged asymptomatic, the first twelve days and the other three weeks after admission. In the authors' experience percutaneous aortic valve replacement can be performed with reasonable safety in patient with severe aortic stenosis at high surgical risk.

EuroSCORE as predictor of in-hospital mortality after percutaneous coronary intervention.

OBJECTIVE: To date, no common risk stratification system is available to predict the risk of surgical or percutaneous myocardial revascularisation in patients with coronary artery disease (CAD). Thus, we sought to assess the European System for Cardiac Operative Risk Evaluation (EuroSCORE) validity to predict in-hospital mortality after percutaneous coronary intervention (PCI). DESIGN, SETTING AND PARTICIPANTS: EuroSCORE was prospectively and systematically assessed in 1173 consecutive patients undergoing PCI in a high-volume single centre between April 2005 and October 2006. MAIN OUTCOME MEASURE: The receiver-operating characteristics (ROC) curve was used to describe performance and accuracy of the EuroSCORE risk model for the prediction of in-hospital mortality after PCI. RESULTS: The EuroSCORE model demonstrated an overall relation between EuroSCORE rank and the incidence of in-hospital mortality, showing consistency in predicting patient risk across many subgroups and levels of global risk. At multivariable logistic regression analysis the EuroSCORE value was an independent in-hospital mortality predictor (p = 0.002) together with left main disease (p = 0.005), procedural urgency (p = 0.001), ACC/AHA C type lesion (p = 0.02) and PCI failure (p = 0.01). The area under the ROC curve for the EuroSCORE system was 0.91 (95% CI 0.86 to 0.97), indicating a good ability of the model to discriminate patients at risk of dying during the index hospitalisation. CONCLUSION: The EuroSCORE risk model, already extensively validated for the prediction of early mortality following open-heart surgery, can also be efficiently utilised in the setting of PCI. The introduction of the EuroSCORE assessment in patients with documented CAD may help to improve the revascularisation strategy decision-making process.

Pexelizumab in ischemic heart disease: a systematic review and meta-analysis on 15,196 patients.

OBJECT: Pexelizumab is a humanized monoclonal antibody inhibiting C5 complement. It has been postulated to improve outcomes in patients undergoing coronary artery bypass surgery and urgent reperfusion therapy for ST elevation myocardial infarction. We aimed at evaluating the risk/benefit profile of pexelizumab (bolus + infusion) versus placebo on top of current approaches in the management of patients with ST elevation myocardial infarction or undergoing coronary artery bypass. METHODS: We conducted a search of BioMedCentral, CENTRAL, mRCT, and PubMed without language restrictions (updated October 2007) for randomized controlled trials. Outcomes of interest were the risk of major adverse events (the composite of all-cause death, myocardial infarction, and thromboembolic stroke), the risk of single end points, and heart failure. RESULTS: Seven trials were included (15,196 patients: 7019 patients with ST elevation myocardial infarction and 8177 undergoing coronary bypass surgery). No benefit of adding pexelizumab was found in the overall analysis for major adverse events (OR 0.91 [0.76-1.09]; P = .29], death (OR 0.79 [0.61-1.03], P = .11], myocardial infarction (OR 1.04 [0.89-1.22]; P = .14), stroke (OR 0.95 [0.66-1.38]; P = .8), heart failure (OR1.0 [0.82-1.22]; P = .99), nor in the settings of patients with ST elevation myocardial infarction treated with mechanical or pharmacologic reperfusion therapy. Pexelizumab was associated with a 26% reduction of the risk of death in the setting of coronary artery bypass (OR 0.74 [0.58-0.94]; P = .01). The number needed to treat was 100. CONCLUSION: Our data ruled out the hypothesis of any benefit of adding pexelizumab on top of currently available therapies for ST elevation myocardial infarction. However, pexelizumab reduces the risk of death in patients undergoing coronary artery bypass grafting.

Percutaneous unprotected left main angioplasty with drug-eluting stents in a nonagenarian: feasible and safe despite recurrent restenosis.

The management of severe coronary artery disease in the very elderly is challenging and the most appropriate revascularization strategy highly debated. To date, coronary artery bypass surgery has been the treatment of choice for significant stenosis of unprotected left main (ULM) coronary. Whether this holds true also in very old patients is unknown. The Authors hereby report the case of a 91-year-old diabetic man who underwent coronary angiography in June 2005 for subacute unstable angina. Angiography disclosed a critical stenoses in the distal unprotected left main, left anterior descending, and distal left circumflex, which were treated with a paclitaxel-eluting stent and a bare-metal stent (BMS), respectively. Four months later, recurrent angina lead to a second angiography which showed critical restenosis in the left anterior descending and significant ostial stenosis in the left circumflex. Another paclitaxel-eluting stent was implanted in the left anterior descending, followed by kissing balloon in the left main, achieving a good angiographic result. Six months later angina recurred again: at angiography diffuse restenosis in the left main, left anterior descending and left circumflex was documented. A crushing technique was thus employed to deliver 2 sirolimus-eluting stents, achieving a satisfactory final result. Since then, and to date for more than 17 months since the last procedure, this nonagenarian has remained free from anginal chest. This case highlights the potentials and drawbacks of percutaneous coronary intervention for unprotected left main disease, suggesting nonetheless, that this revascularization strategy can be safely repeated even in elderly patients.