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Background: The genetic basis of stroke susceptibility remains to be elucidated. STR1 quantitative trait locus (STR1/QTL) was identified on rat chromosome 1 of stroke-prone spontaneously hypertensive rat (SHRSP) upon Japanese-style stroke-permissive diet (JD), and it contributes to 20% of the stroke phenotype variance., Methods and Results: Nine hundred eighty-six probe sets mapping on STR1 were selected from the Rat RAE230A array and screened through a microarray differential expression analysis in brains of SHRSP and stroke-resistant SHR (SHRSR) fed with either regular diet or JD. The gene encoding Ndufc2 (NADH dehydrogenase [ubiquinone] 1 subunit), mapping 8 Mb apart from STR1/QTL Lod score peak, was found significantly down-regulated under JD in SHRSP compared to SHRSR. Ndufc2 disruption altered complex I assembly and activity, reduced mitochondrial membrane potential and ATP levels, and increased reactive oxygen species production and inflammation both in vitro and in vivo. SHRSR carrying heterozygous Ndufc2 deletion showed renal abnormalities and stroke occurrence under JD, similarly to SHRSP. In humans, T allele variant at NDUFC2/rs11237379 was associated with significant reduction in gene expression and with increased occurrence of early-onset ischemic stroke by recessive mode of transmission (odds ratio [OR], 1.39; CI, 1.07-1.80; P=0.012). Subjects carrying TT/rs11237379 and A allele variant at NDUFC2/rs641836 had further increased risk of stroke (OR=1.56; CI, 1.14-2.13; P=0.006)., Conclusions: A significant reduction of Ndufc2 expression causes complex I dysfunction and contributes to stroke susceptibility in SHRSP. Moreover, our current evidence may suggest that Ndufc2 can contribute to an increased occurrence of early-onset ischemic stroke in humans., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Aims: To compare the effects of two thrombus aspiration devices, the manual catheter Export® and the more complex and expensive mechanical Angiojet®, on several indices of reperfusion in acute ST-elevation myocardial infarction (STEMI)., Methods and Results: Clinical, hemodynamic and procedural characteristics of 185 STEMI patients, randomized to treatment with Export (n=95) or Angiojet (n=90) during primary percutaneous coronary intervention (PPCI) were analyzed. The primary endpoint was ST-segment elevation reduction 90 min after culprit vessel re-opening. Secondary endpoints included variations in some angiographic parameters (TIMI Flow, TIMI Frame Count and Myocardial Blush Grade) and Infarct Size and Severity at myocardial scintigraphy. A significant reduction in ST-elevation was observed in both groups after PPCI without significant differences between the two groups. No significant difference between Angiojet vs. Export was observed in ST-segment resolution >50% and ≥ 70%, in TIMI Flow, TIMI Frame Count and Myocardial Blush Grade before vs. after PPCI and in Infarct Size and Severity., Conclusions: PPCI with thrombus aspiration was effective in both groups of patients, without differences in myocardial reperfusion and necrosis indices. These results could support the routine use of manual devices during PPCI, reserving the more expensive Angiojet in case of manual device failure and persistent or massive intracoronary thrombosis, with favorable implications in terms of cost containment., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Thoracic aortic aneurysm/dissection (TAAD) is a potential lethal condition with a rising incidence. This condition may occur sporadically; nevertheless, it displays familial clustering in >20% of the cases. Family history confers a six- to twentyfold increased risk of TAAD and has to be considered in the identification and evaluation of patients needing an adequate clinical follow-up. Familial TAAD recognizes a number of potential etiologies with a significant genetic heterogeneity, in either syndromic or nonsyndromic forms of the manifestation. The clinical impact and the management of patients with TAAD differ according to the syndromic and nonsyndromic forms of the manifestation. The clinical management of TAAD patients varies, depending on the different forms. Starting from the description of patient history, in this paper, we summarized the state of the art concerning assessment of clinical/genetic profile and therapeutic management of TAAD patients.

Objective: Visceral ischemia can be a potentially life-threatening complication of intra-aortic balloon pump (IABP) support. A shorter IABP catheter might lead to a reduction of visceral complications. In this animal study, we evaluate the effects of a 35-mL short catheter in comparison with a 40-mL standard-sized catheter., Methods: Eighteen healthy swine underwent 120-minute ligation of the left anterior descending coronary artery followed by 6 hours of reperfusion being supported by either a short IABP catheter (short group) (n = 6) or a long IABP catheter (long group) (n = 6) or with no assistance (controls) (n = 6). Hemodynamics, visceral and coronary flows, as well as biochemical markers were evaluated throughout the different phases of the protocol., Results: Mesenteric flows increased significantly at reperfusion (P < 0.001 both) remaining constant afterward (all, P > 0.05) in the short group, while remaining significantly lower in the long group at the start of reperfusion, remaining constantly lower than the short group and controls (P < 0.001 vs short, P < 0.003 vs controls). In both long and short groups, catheters improved renal flows at reperfusion (P < 0.001 both) without any further variation (P > 0.05). In the short group, the flows were higher during the whole of reperfusion (all, P < 0.05). Intra-aortic balloon pump support improved hemodynamic indices and coronary blood flows during reperfusion to a similar extent in both the small and the long group (P > 0.05)., Conclusions: The short IABP catheter proved to be as effective as the standard-sized catheter in supporting hemodynamics and coronary circulation. Furthermore, it even improves visceral flows in comparison with conventional IABP catheters.

Background: The study sought to determine the impact of high residual platelet reactivity (HRPR) on long-term cardiac mortality in diabetic patients treated with PCI for CTO. No data exist about the impact of HRPR after 600 mg clopidogrel loading on long-term clinical outcome in patients with diabetes mellitus and treated with percutaneous coronary angioplasty (PCI) for chronic total occlusion (CTO)., Methods: From the Florence CTO-PCI registry, we identified consecutive diabetic patients with available in vitro platelet reactivity assessment by light transmittance aggregometry after a loading dose of 600 mg of clopidogrel. HRPR was defined as residual platelet aggregation by 10 μmol/L ADP test ≥70%. The primary end point of the study was long-term cardiac mortality., Results: Two-hundred and three diabetic patients underwent CTO-PCI. The incidence of HRPR was 23%. The 3-year cardiac survival was lower in the HRPR group than the low residual platelet reactivity (LRPR) group (70 ± 7% and 92 ± 3%, respectively; p=0.001). Within the oral antidiabetic patients there were no significant differences in long-term survival between HRPR and LRPR groups. Conversely, the association of insulin therapy and HRPR was related to a dramatic decrease in survival compared to the LRPR group (34 ± 14% vs. 89 ± 4%; p<0.001). At multivariable analysis insulin therapy (HR 4.31; p=0.001) and HRPR (HR 3.26; p=0.004) were significantly related to long-term mortality, while completeness of revascularization was inversely related to cardiac mortality (HR 0.40; p=0.029)., Conclusion: HRPR is a strong marker of increased risk of cardiac death in patients with DM who underwent PCI for CTO., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Veno-arterial extracorporeal membrane oxygenation (VA ECMO) represents a therapeutic option in patients with refractory cardiogenic shock (RCS). This strategy is limited to a restricted number of centres with capabilities for implanting VA ECMO and management patients on this support. We report on the initial experience of our ECMO referral centre for patients with RCS., Methods: We retrospectively analysed our ECMO data registry for RCS of 14 patients treated with VA ECMO, consecutively admitted to our intensive cardiac care unit (ICCU), which is an ECMO referral centre., Results: Six patients (6/14, 42%) came from peripheral centres, four were transferred to our ICCU directly. During ICCU stay, four patients died (28.5%) due to multi-organ failure, seven showed a complete recovery while one underwent cardiac transplantation. The remaining two patients died while waiting for cardiac transplantation because of cerebral haemorrhage. The 30-day overall mortality rate was 42.8%, all survivors showed a good neurologic outcome., Conclusions: In our series, the survival rate of RCS patients supported by VA ECMO is high (57%) and the transfer of RCS patients is feasible and safe. Our data support that a network for RCS is needed to transfer patients in well experienced centres even on ECMO support.

Background: Most central venous catheter (CVC)-related deep vein thromboses (DVT) are asymptomatic and their incidence and clinical relevance are still under debate. Data on CVC-related fibrin sheaths are scarce. We investigated the incidence of asymptomatic DVT and fibrin sheaths in cancer patients with long-term CVC implantation who underwent Doppler ultrasound surveillance at 1, 6, and 12 months after implantation. Effects of low-weight molecular heparin (LWMH) therapy on DVT and fibrin sheaths were also analyzed., Material and Methods: This prospective study was performed on a large cohort (n = 400) of patients with cancer aged >18 requiring long-term CVC implantation for chemotherapy infusion. CVC was implanted by a trained qualified staff, according to standardized protocol in a specific surgery. Patients underwent ultrasound examination at 1 and 6 months after CVC implantation to detect 'early' (1 month) and 'late' (6 months) asymptomatic DVT or fibrin sheaths incidence. Sixty-nine patients underwent US examination also 12 months after CVC implantation., Results: The incidence of CVC-related thrombosis was 0.10 events per 1000 catheter days. Anticoagulation therapy with LWMH resolved 50% of DVT, but no CVC needed removing. Incidence of new onset fibrin sheaths was 0.71 events per 1000 catheter days. Fibrin sheaths resolution occurred independently of LWMH therapy., Discussion: The incidence of asymptomatic DVT in our patients with long-term CVC is very low and does not represent per se an indication for removal of functioning CVC in patients with cancer. Fibrin sheaths are frequent (13%) and never associated with CVC dysfunction., Conclusion: Asymptomatic DVT and fibrin sheaths do not represent per se an indication for removal of functioning CVC in cancer patients who need central vein access., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Few data are so far available on the relation between increased glucose values and insulin resistance and mortality at short-term in patients with acute heart failure (AHF)., Methods: The present investigation, performed in 409 consecutive patients with AHF complicating acute coronary syndrome (ACS), was aimed at assessing the prognostic role of admission glycaemia and acute insulin resistance (as indicated by the Homeostatic Model Assessment - HOMA index) for death during Intensive Cardiac Care (ICCU) stay. Admission glucose tertiles were considered., Results: In our series, diabetic patients accounted for the 33%. Patients in the third glucose tertiles exhibited the lowest LVEF (both on admission and at discharge), a higher use of mechanical ventilation, intra-aortic balloon pump and inotropic drugs and the highest in-ICCU mortality rate. In the overall population, hyperglycaemic patients (both diabetic and non diabetic) were 227 (227/409, 55.5%). Admission glycaemia was an independent predictor of in-ICCU mortality, together with admission LVEF and eGFR, while acute insulin resistance (as indicated by HOMA-index) was not associated with early death. The presence of admission hyperglycaemia in non-diabetic patients was independently associated with in-ICCU death while hyperglycaemia in diabetic patients was not., Conclusions: According to our results, hyperglycaemia is a common finding in patients with ACS complicated by AHF and it is an independent predictor of early death. Non-diabetic patients with hyperglycaemia are the subgroup with the highest risk of early death., (Copyright © 2015 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Patients with renal impairment have decreased excretion of uric acid, thus being particularly prone to having elevated serum uric acid concentrations. No data are available on the long-term prognostic role of uric acid in patients with ST-elevation myocardial infarction (STEMI) and renal dysfunction, submitted to percutaneous coronary intervention (PCI). We therefore prospectively assessed, in 329 patients with STEMI and renal dysfunction (admission estimated glomerular filtration rate <60 ml/min/1.73 m), all submitted to PCI, whether uric acid levels are associated with increased mortality at 1-year postdischarge follow-up.Patients in the third tertile of uric acid showed a higher BMI (P = 0.014), a higher incidence of hypertension (P = 0.029), and two or more comorbidities (P = 0.034). The highest incidence of bleeding and of acute kidney injury was detectable in patients in the third tertile (P = 0.011 and P < 0.001, respectively) who showed the highest mortality rate at 1-year postdischarge follow-up (P = 0.008). At Cox regression analysis, uric acid was an independent predictor of 1-year postdischarge mortality (hazard ratio 1.26, 95% confidence interval 1.06-1.51, P = 0.011).In STEMI patients with estimated glomerular filtration rate below 60 ml/min/1.73 m treated with PCI, uric acid helps in identifying a subset of patients at a higher risk of bleeding and acute kidney injury. Increased uric acid is an independent prognostic risk factor for 1-year mortality. Further studies performed in larger cohorts of patients are needed to confirm our findings and to evaluate whether lowering uric acid in these patients is beneficial.

Background: The TIPTOP (Early Short-term Doxycycline Therapy In Patients with Acute Myocardial Infarction and Left Ventricular Dysfunction to Prevent The Ominous Progression to Adverse Remodelling) trial demonstrated that a timely, short-term therapy with doxycycline is able to reduce LV dilation, and both infarct size and severity in patients treated with primary percutaneous intervention (pPCI) for a first ST-elevation myocardial infarction (STEMI) and left ventricular (LV) dysfunction. In this secondary, pre-defined analysis of the TIPTOP trial we evaluated the relationship between doxycycline and plasma levels of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs)., Methods: In 106 of the 110 (96%) patients enrolled in the TIPTOP trial, plasma MMPs and TIMPs were measured at baseline, and at post-STEMI days 1, 7, 30 and 180. To evaluate the remodeling process, 2D-Echo studies were performed at baseline and at 6months. A (99m)Tc-SPECT was performed to evaluate the 6-month infarct size and severity., Results: Doxycycline therapy was independently related to higher plasma TIMP-2 levels at day 7 (p<0.05). Plasma TIMP-2 levels above the median value at day 7 were correlated with the 6-month smaller infarct size (3% [0%-16%] vs. 12% [0%-30%], p=0.002) and severity (0.55 [0.44-0.64] vs. 0.45 [0.29-0.60], p=0.002), and LV dilation (-1ml/m(2) [from -7ml/m(2) to 9ml/m(2)] vs. 3ml/m(2) [from -2ml/m(2) to 19ml/m(2)], p=0.04), compared to their counterpart., Conclusions: In this clinical setting, doxycycline therapy results in higher plasma levels of TIMP-2 which, in turn, inversely correlate with 6month infarct size and severity as well as LV dilation., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Patients' response to dual antiplatelet therapy (DAPT) is subject to variations and its monitoring allows to individualize this therapy. In this study, we evaluated if a strategy of tailored DAPT after platelet function testing could reduce high on-treatment platelet reactivity (HPR) and improve outcome of patients treated with stent implantation. In 257 patients undergoing percutaneous angioplasty, platelet function was measured by light transmittance aggregometry (LTA) using 10 µM/L adenosine-diphosphate (ADP) and 1 mM arachidonic acid (AA) as agonists. Patients with HPR by ADP (≥70%) were switched to double-dose clopidogrel, ticlopidine, prasugrel or ticagrelor; in patients with HPR by AA (≥20%) acetylsalicylic acid dose was increased if not contraindicated. Platelet function analysis was repeated 48 hours after therapy variation. At 20-month follow-up major adverse cardiovascular events (MACE) and bleedings were assessed. HPR was detected in 97/257 (37.7%) patients: 69/257 (26.8%) had HPR by ADP and 71/257 (27.6%) had HPR by AA. In patients with HPR by ADP or by AA, tailored DAPT determined a significant reduction in residual platelet reactivity. No significant difference in MACE or bleeding occurrence was documented in HPR patients treated with tailored DAPT vs. those without HPR. HPR patients treated with tailored DAPT had significant lower follow-up MACE and deaths vs. 139 HPR patients not switched, even after propensity score analysis. These results suggest that a DAPT tailored on platelet testing can improve antiplatelet response in HPR patients, possibly reducing their thrombotic events to a level similar to non-HPR patients, without increasing the risk of bleeding.

Background: Critically ill patients appear to be at high risk of developing deep vein thrombosis (DVT) and pulmonary embolism during their stay in the intensive care unit (ICU). However, little is known about the clinical course of venous thromboembolism in the ICU setting. We therefore evaluated, through a systematic review of the literature, the available data on the impact of a diagnosis of DVT on hospital and ICU stay, duration of mechanical ventilation and mortality in critically ill patients. We also tried to determine whether currently adopted prophylactic measures need to be revised and improved in the ICU setting., Materials and Methods: MEDLINE and EMBASE databases were searched up to week 4 of June 2012. Two reviewers selected studies and extracted data. Pooled results are reported as relative risks and weighted mean differences and are presented with 95% confidence intervals (CI)., Results: Seven studies for a total of 1,783 patients were included. A diagnosis of DVT was frequent in these patients with a mean rate of 12.7% (95% CI: 8.7-17.5%). DVT patients had longer ICU and hospital stays compared to those without DVT (7.28 days; 95% CI: 1.4-13.15; and 11.2 days; 95% CI: 3.82-18.63 days, respectively). The duration of mechanical ventilation was significantly increased in DVT patients (weighted mean difference: 4.85 days; 95% CI: 2.07-7.63). DVT patients had a marginally significant increase in the risk of hospital mortality (relative risk 1.31; 95% CI: 0.99-1.74; p=0.06), and a not statistically significant increase in the risk of ICU mortality (RR 1.64; 95% CI: 0.91-2.93; p=0.10)., Conclusions: A diagnosis of DVT upon ICU admission appears to affect clinically important outcomes including duration of ICU and hospital stay and hospital mortality. Larger, prospective studies are warranted.

Objectives: This study sought to investigate the efficacy of prasugrel compared with clopidogrel in clopidogrel nonresponders., Background: Clopidogrel nonresponsiveness is a strong marker of the risk of cardiac death and stent thrombosis after a percutaneous coronary intervention (PCI). It is unknown whether clopidogrel nonresponsiveness is a nonmodifiable risk factor or whether prasugrel with more potent and predictable platelet inhibition as measured by ex vivo techniques is associated with a positive effect on clinical outcome., Methods: The RECLOSE-3 (REsponsiveness to CLOpidogrel and StEnt thrombosis) study screened clopidogrel nonresponders after a 600-mg loading dose of clopidogrel. Clopidogrel nonresponders switched to prasugrel (10 mg/day) the day of the PCI, and an adenosine diphosphate (ADP) test (10 μmol/l of ADP) was performed 6 days after the PCI. The primary endpoint was 2-year cardiac mortality. Patient outcome was compared with the RECLOSE-2-ACS study., Results: We screened 1,550 patients, of whom 302 were clopidogrel nonresponders. The result of the ADP test was 77.6 ± 6.2%. After switching to prasugrel, the ADP test result decreased to 47.1 ± 16.8%. The 2-year cardiac mortality rate was 4% in the RECLOSE-3 study and 9.7% in nonresponders of the RECLOSE-2-ACS study (p = 0.007). The definite and probable stent thrombosis rates were 0.7% and 4.4%, respectively (p = 0.004). On multivariable analysis, prasugrel treatment was related to the risk of 2-year cardiac death (hazard ratio: 0.32, p = 0.036)., Conclusions: Clopidogrel nonresponsiveness can be overcome by prasugrel (10 mg/day), and optimal platelet aggregation inhibition on prasugrel treatment is associated with a low rate of long-term cardiac mortality and stent thrombosis., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The relationship between troponin and atrial fibrillation (AF) without acute coronary syndrome is still unclear. We sought to investigate the presence of coronary atherosclerosis and adverse outcomes in patients with AF., Methods: Consecutive patients with recent-onset AF and without severe comorbidities were enrolled between 2004 and 2013. Patients with a troponin rise or with adverse outcomes were considered for coronary angiography and revascularization when "critical" stenosis (≥70%) was recognized. Propensity score matching was performed to adjust for baseline characteristics; after matching, no differences existed between the groups of patients with or without troponin rise. The primary end point was the composite of acute coronary syndrome, revascularization, and cardiac death at 1- and 12-month follow-ups., Results: Of 3627 patients enrolled, 3541 completed the study; 202 (6%) showed troponin rise; and 91 (3%), an adverse outcome. In the entire cohort, on multivariate analysis, the odds ratio for the occurrence of the primary end point of troponin rise was 14 (95% confidence interval [CI], 10-23; P<.001), and that of known coronary artery disease was 3 (CI, 2-5; P=.001). In the matching cohort, the odds ratio of troponin rise was 10 (CI, 4-22; P<.001), and that of TIMI score greater than 2 was 4 (CI, 2-9; P≤.001). In the entire cohort, patients with or without troponin rise achieved the primary end point in 38 (19%) and 43 (1%) patients, respectively (P<.001). Stroke occurred in 4 (2%) and 20 (1%), respectively (P=.018). Critical stenosis and revascularization account for 23 (12%) and 15 (1%), respectively (P<.001). In the matching cohort, results were confirmed, but incidence of stroke was comparable., Conclusions: Patients with recent-onset AF and troponin rise showed higher prevalence of coronary atherosclerosis and adverse cardiac events. Stroke per se did not succeed in justifying the high morbidity. Thus, beyond stroke, coronary atherosclerosis might have a pivotal role in poor outcomes., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Aim: The present investigation was aimed at assessing the prognostic impact of renal dysfunction rate in STEMI patients submitted to thrombectomy (TP)., Methods: Out of 1268 consecutive ST elevation myocardial infarction (STEMI) patients treated with pPCI from January 1rst 2004 to December 31th 2012 in our hospital 671 patients (52.9%) underwent adjunctive thrombus aspiration and constituted the study population. Patients were divided into three groups according to eGFR: group 1 included patients with eGFR>60 mL/min/m2, group 2 eGFR>30 mL/min/m2 and <60 mL/min/m2, group 3 eGFR<30 mL/min/m2. The rate of utilization of thrombectomy, the rate of pPCI failure and the incidence of major bleeding were assessed in each subgroup. Patients in group 3 and group 2 were less likely to be submitted to TP, while more than 50% of patients with normal eGFR underwent TP (overall P=0.019). The rate of pPCI failure was significantly higher in group 2 and 3 when compared to group 1 (P=0.002). Worsening renal failure was associated with a higher mortality rate both at ICCU and at 1 year follow-up (P<0.001 and P<0.001, respectively). A higher incidence of major bleedings was reported in group 2 and group 3, despite the lower administration of glycoprotein IIb/IIIa inhibitors (P<0.001). Moderate and severe renal impairment was associated with a higher mortality rate both at ICCU and at 1 year follow-up (P<0.001 and P<0.001, respectively)., Conclusion: Thrombus aspiration is less like to be performed among patients with impaired renal function. Despite thrombus aspiration patients with reduced eGFR showed a higher incidence of pPCI failure.

In clinical practice, acidotic patients with acute cardiogenic pulmonary edema (ACPE) are commonly considered more severe in comparison with nonacidotic patients, and data on the outcome of these patients treated with noninvasive pressure support ventilation (NIV) are lacking.The present investigation was aimed at assessing whether acidosis on admission (pH < 7.35) was associated with adverse outcome in 65 consecutive patients with ACPE treated with NIV and admitted to our Intensive Cardiac Care Unit (ICCU).In our population, 28 patients were acidotic (28 of 65, 43.1%), whereas 41 patients were not (37 of 65, 56.9%). According to the Repeated Measures General Linear Model, pCO2 values significantly changed throughout the 2-h NIV treatment (P = 0.019) in both groups (P = 0001). In acidotic patients, pCO2 significantly decreased (51.9 ± 15.3 → 47.0 ± 12.8 → 44.8 ± 12.7), whereas they increased in the nonacidotic subgroup (36.8 ± 6.5 → 36.9 ± 7.2 → 37.6 ± 6.4). No difference was observed in intubation rate between acidotic (eight patients, 28.6%) and nonacidotic patients (12 patients, 32.4%) (P = 0.738). In-ICCU mortality rate did not differ between (13 patients, 35.1%) and nonacidotic patients (nine patients, 32.1%) (P = 0.801).Our data strongly suggest that in patients with severe ACPE treated with NIV, the presence of acidosis is not associated with adverse outcomes (early mortality and intubation rates) in these patients.

Background: Patients presenting with acute coronary syndrome (ACS) who require urgent/emergency coronary artery bypass grafting (CABG) are increasing, as is the complexity of their clinical characteristics, one of which is advanced age. We evaluated the prognostic role of age in patients undergoing urgent/emergency cardiac surgery for ACS., Methods: From January to December 2013, 452 consecutive patients underwent CABG at our institution. Among these, 213 presented with ACS, were enrolled in the study and divided into tertiles of age: First: 40-65 years old (n=73), Second: 66-74 (n=70), Third: 75-89 (n=70). Patients were followed post-operatively for 30 days., Results: No differences between tertiles were found for baseline clinical and angiographic characteristics. Off-pump interventions were 67.6%. Older patients more frequently required an associate intervention to CABG for a mechanical complication of ACS. Overall 30-day all-cause mortality was 4.7% (n=10); 0.6% (n=1) in patients undergoing isolated CABG (n=168, 78.9%). The STEMI diagnosis was an independent risk factor for 30-day mortality, and age was not., Conclusions: The 30-day mortality rate of older ACS patients who undergo urgent/emergency CABG is comparable to that of younger ones. Pre-operative risk assessment should rely on evaluation of the clinical complexity of each patient independent of their chronological age, to customise the therapeutic strategy., (Copyright © 2015 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Dietary habits are widely reported to play a primary role in the occurrence of coronary artery disease (CAD). Cardiac rehabilitation is a multidisciplinary intervention that includes nutritional education. Proper nutrition plays an important role in cardiovascular health outcomes and in decreasing morbidity and mortality of cardiovascular diseases (CVD) as highlighted in the literature. The aim of this study was to assess the efficacy of an educational program to improve the diet of cardiac rehabilitation patients compared to usual treatment. 160 patients with CAD, (124 M, 36 F) were randomized into two groups. Data analysis was conducted on 133 patients (11 % dropped out). All enrolled patients attended two educational seminars about proper nutrition and cardiovascular prevention, and completed a questionnaire about dietary habits (before CAD). The Body Mass Index (BMI) was calculated, and basal glycaemia and plasma lipids were assessed at the beginning and at the end of the study (12 months after hospital discharge). The intervention group patients underwent a mid-term evaluation of nutrient intakes, BMI, and received a personalized educational reinforcement by a dietitian. At the end of the study, the intervention group was shown to have significantly reduced their daily caloric intake (reduction of total proteins, total fat, carbohydrate, alcohol), and showed a significant reduction of weight and BMI compared to the control group. Individual nutritional counseling session as a reinforcement of a standard educational program is effective in reducing caloric intake and BMI, which may reduce cardiovascular risk factors in cardiovascular patients.

Introduction: Limited data are available on the natural history of high on treatment platelet reactivity (HPR) by arachidonic acid and ADP - markers of unfavorable prognosis in acute coronary syndrome patients -., Material and Methods: In a cohort of acute coronary syndrome male patients (n=101), we evaluated the time-course of HPR by ADP (platelet aggregation by 10μM ADP≥70%) and arachidonic acid (platelet aggregation by 1mmol arachidonic acid≥20%) measuring platelet function in the acute phase (T0), at 6months (T1) and 1year (T2)., Results: We identified persistent (HPR at T0,T1 and T2), acute non persistent (HPR only at T0), and late (HPR only at T1 or T2). Patients with persistent HPR by ADP were more frequently with higher values of BMI. Patients carrying CYP2C19*2 variant were more prevalent in the group of persistent HPR (33%). Significant higher values of immature platelet fraction and high immature platelet fraction at 6 and 12months and mean platelet volume were present in patients with late HPR. Immature platelet fraction was the only variable significantly associated with late HPR by ADP at multivariate analysis (OR=1.6 (1.08-2.3), p=0.016). Patients with persistent HPR by arachidonic acid were more frequently diabetics. Immature platelet fraction at 6months and high immature platelet fraction at 6 and 12months were the parameters associated with late HPR by AA (OR=1.4 (1.0-1.9), p=0.036; OR=1.5 (1.08-2.4), p=0.05; OR=4.9 (1.3-18.8), p=0.018, respectively)., Conclusions: About 25% of 101 patients has persistent HPR; they are more frequently diabetics, overweight or carriers of CYP2C19*2. The occurrence of an inflammatory state, indicated by the increase of immature platelet fraction, is associated with the occurrence of late HPR., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Lactate, as a metabolite of easy and quick assessment, has been studied over time in critically ill patients in order to evaluate its prognostic ability. The present review is focused on the prognostic role of lactate levels in acute cardiac patients (that is with acute coronary syndrome, cardiogenic shock, cardiac arrest, non including post cardiac surgery patients). In patients with ST-elevation myocardial infarction treated with mechanical revascularization, hyperlactatemia identified a subset of patients at higher risk for early death and in-hospital complications, being strictly related mainly to hemodynamic derangement. The prognostic impact of hyperlactatemia on mortality has been documented in patients with cardiogenic shock and in those with cardiac arrest even if there is no cut-off value of lactate to be associated with worse outcome or to guide resuscitation or hemodynamic management. Therapeutic hypothermia seems to affect per se lactate values which have been shown to progressively decrease during hypothermia. The mechanism(s) accounting for lactate levels during hypothemia seem to be multiple ranging from the metabolic effects of reduced temperatures to the hemodynamic effects of hypothermia (i.e., reduced need of vasopressor agents). Serial lactate measurements over time, or lactate clearance, have been reported to be clinically more reliable than lactate absolute value also in acute cardiac patients. Despite differences in study design, timing of lactate measurements and type of acute cardiac conditions (i.e., cardiogenic shock, cardiac arrest, refractory cardiac arrest), available evidence strongly suggests that higher lactate levels can be observed on admission in non-survivors and that higher lactate clearance is associated with better outcome.

Background: No data are so far available on the association between glycaemic variability and outcomes in patients with cardiogenic shock (CS) following ST elevation myocardial infarction (STEMI)., Methods: We assessed the relationship between glycaemic variability and mortality, both short term and long term, in 67 consecutive patients with cardiogenic shock following STEMI admitted to our Intensive Cardiac Care Unit. Glycaemic variability was measured in the first 48 h by means of standard deviation (SD) of glucose values and the mean absolute glucose change per hour (MAGC) defined as the sum of all absolute glucose change divided by the time in hours., Results: Lower glycaemic variability was observed in survivors when compared with nonsurvivors, as indicated by lower values of SD and MAGC, respectively. In Cox regression analysis, MAGC and SD were independent predictors of death (MAGC: adjusted hazard ratio [HR]: 8.60, 95% confidence interval [CI]: 2.21-33.41, p = 0.002; SD: adjusted HR: 6.64, 95% CI: 1.92-22.99, p = 0.003), as well as peak glycaemia (adjusted HR: 1.95, 95% CI: 1.20-3.15, p = 0.007)., Conclusions: According to our results, in patients with CS following acute myocardial infarction, early glycaemic variability is an independent predictor of mortality. Further studies are needed to confirm our results in larger cohorts and eventually to assess the effect of strategies specifically targeting glucose variability reduction on mortality., (© The Author(s), 2015.)

Background: We investigated the role of surgical ablation targeting the autonomous nervous system during a Cox-Maze IV procedure in the maintenance of sinus rhythm at long-term follow-up., Methods: The patient population consisted of 519 subjects with persistent or long-standing persistent atrial fibrillation (AF) undergoing radiofrequency Maze IV during open heart surgery between January 2006 and July 2013 at three institutions without (Group 1) or with (Group 2) ganglionated plexi (GP) ablation. Recurrence of atrial fibrillation off-antiarrhythmic drugs was the primary outcome. Predictors of AF recurrence were evaluated by means of competing risk regression. Median follow-up was 36.7 months., Results: The percentage of patients in normal sinus rhythm (NSR) off-antiarrhythmic drugs did not differ between groups (Group 1-75.5%, Group 2-67.8%, p = 0.08). Duration of AF ≥ 38 months (p = 0.01), left atrial diameter ≥ 54 mm (0.001), left atrial area ≥ 33 cm(2) (p = 0.005), absence of connecting lesions (p= 0.04), and absence of right atrial ablation (p < 0.001) were independently associated with high incidence of AF recurrence. In contrast the absence of GP ablation was not a significant factor (p = 0.12)., Conclusions: GP ablation did not prove to be beneficial for postoperative stable NSR. A complete left atrial lesion set and biatrial ablation are advisable for improving rhythm outcomes. Randomized controlled trials are necessary to confirm our findings., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Little is known regarding the evolution of coronary aneurysms. We report on a rapidly growing coronary pseudoaneurysm with the aim to underline the reasons for rapid coronary aneurysm enlargement and the different therapeutics options available to face this rare clinical condition., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Despite beneficial effects of physical activity on cardiovascular risk, discordant data on elite athletes (high atherosclerotic damage in activity comprising strenuous exertion) and retired sportsmen are reported in the literature., Hypothesis: We hypothesize that long-lasting daily physical activity could affect the morphology and function of the carotid and femoral vessel walls differently, as assessed in elite male athletes aged 20 to 30 years compared with age- and sex-matched healthy controls., Study Design: Retrospective case-control study., Level of Evidence: Level 3., Methods: Sixty male subjects (30 athletes and 30 controls) underwent medical examination for ankle brachial index, augmentation index (AIX) and AIX corrected for heart rate (AIXr), peripheral arterial tonometry (PAT), and intima media thickness and pulse wave velocity assay at common carotid (carotid-intima media thickness [c-IMT], carotid-pulse wave velocity [c-PWv]) and femoral arteries (femoral-intima media thickness [f-IMT], femoral-pulse wave velocity [f-PWv]) assessed by ultrasonography using Doppler ultrasound., Results: Athletes showed a significantly lower heart rate (HR) at rest and a better lipid profile than controls. In athletes, c-PWv (5.87 ± 0.80 vs 6.62 ± 1.02 m/s, P = 0.001) and f-PWv (8.96 ± 1.29 vs 7.89 ± 1.39, P = 0.002) were, respectively, significantly lower and higher than values found in controls; accordingly, carotid AIX (4.03 ± 6.21 vs 7.81 ± 5.21, P = 0.003) and femoral AIX (8.56 ± 10.21 vs 6.09 ± 7.95, P = 0.042) were lower and higher than control values, even after correction for heart rate (P = 0.03). On the other hand, IMT values were significantly higher in controls than in athletes (c-IMT, P < 0.0001; f-IMT, P < 0.0001). A positive significant correlation between HR and c-IMT and f-IMT (r = 0.527, P < 0.001 and r = 0.539, P < 0.0001, respectively) and between HR and c-PWv (r = 0.410, P = 0.01) was found when controls and athletes were considered as a whole group. Soccer players showed lower PAT values in comparison with controls (P = 0.002)., Conclusion: Elite sports positively affect c-IMT, f-IMT, and carotid PWv and AIX but not femoral PWv, AIX, AIXr, or PAT., Clinical Relevance: Physical activity affects vascular beds in elite athletes differentially, depending on the rate of superior or inferior limb involvement in different sports. In soccer players, physical activity has a protective effect on carotid and femoral vessel walls but worsens femoral arterial and endothelial function. These findings highlight how different results can be shown on carotid and femoral districts, when these vascular districts are differently stressed during sport activity.

The aim of this study was the identification of the optimal cutoff value of high residual platelet reactivity (HRPR) assessed by light transmission aggregometry (LTA) in the responsiveness to clopidogrel and stent thrombosis 2-acute coronary syndrome (RECLOSE 2-ACS) patient cohort to discriminate patients with and without major adverse cardiac events (MACE) and cardiac death at 2 years. The RECLOSE 2-ACS study included 1,789 patients with ACS who underwent LTA after clopidogrel loading. A post hoc cutoff value for HRPR was defined with the ROC curve and the Youden index and compared with the protocol-defined cutoff of 70 %. By ROC analysis, 63 % resulted the optimal cutoff value to predict both MACE and cardiac death at 2 years follow-up. A significant sensitivity improvement for the ROC-based cutoff value was noted (p < 0.001), at the price of lower specificity and predictive accuracy. The latter were 81 % for MACE and 85 % for cardiac death with the 70 % cutoff, while the respective figures were 73 and 75 % with the 63 % cutoff. The areas under the curve were virtually identical with the 70 and 63 % cutoffs both for MACE (0.71) and cardiac death (0.79). A residual platelet reactivity cutoff of 70 % by LTA, compared to the ROC-based cutoff of 63 %, allows for the identification of a subset of patients at very high risk of adverse ischemic events, making LTA-ADP test more acceptable in clinical practice for the identification of subjects at risk than other platelet function assays with broader definitions of HRPR.

Backgrounds/objectives: We aimed at assessing the impact of increased HbA1c (≥6.5%) on 1-year mortality in consecutive patients with ST Elevation Myocardial Infarction (STEMI) submitted to primary percutaneous coronary intervention (PCI)., Methods: The study population comprises 1205 STEMI patients treated with primary PCI and consecutively admitted to our Center from 1 January 2004 to 31 December 2011., Results: Two hundred and seventy-six patients with previously diagnosed diabetes (276/1205, 22.9%, Group A), 78 patients without previously known diabetes and HbA1c at least 6.5% (78/1205, 6.5%, Group B) and 851 patients without previously known diabetes and HbA1c less than 6.5% (851/1205, 70.1%, Group C).At Cox regression analysis, HbA1c at least 6.5% was not related to 1-year postdischarge mortality in patients with previously diagnosed diabetes nor in those without previously known diabetes.Kaplan-Meier survival curve analysis showed that patients in Group A exhibited the lowest survival rate, while patients in Group B (i.e. patients without previously known diabetes and with HbA1c ≥6.5%) showed a significant reduction in their survival rate since 6 months after discharge., Conclusion: In a large series of STEMI patients submitted to primary PCI, HbA1c levels were not related with outcomes at multivariable analysis.

Although there are extensive published data regarding venous-arterial (VA) ECMO, particularly in the pediatric population, there is a paucity of data (mainly including case reports and observational studies) delineating the role of echocardiography in the management of adult patients supported by venous-venous (VV) ECMO. The present review is aimed at specifically addressing the rationale for echocardiography use in patients supported by VV-ECMO and at summarizing the available evidence on this topic. Based on the available evidence and on the experience of our group, practical considerations on the use of echocardiography in adult patients on VV-ECMO support are reported. To date, echocardiography is mainly used for selecting the type of ECMO (VA vs VV), monitoring cannulation and the early detection of complications, but it is underused in patients supported by VV-ECMO. Nevertheless, in these patients, this methodology can provide useful information in monitoring cardiac function, cannula positioning, pericardial fluid (for early detection of tamponade) during ECMO support, and therefore it can contribute to the integrated assessment and management of these complex patients. There is a clinical need to elaborate shared protocols for echocardiography use during VV ECMO support, particularly at this time when advanced echocardiography is gaining interest among intensivists.

Background: Short-term impacts of high temperatures on the elderly are well known. Even though Italy has the highest proportion of elderly citizens in Europe, there is a lack of information on spatial heat-related elderly risks., Objectives: Development of high-resolution, heat-related urban risk maps regarding the elderly population (≥ 65)., Methods: A long time-series (2001-2013) of remote sensing MODIS data, averaged over the summer period for eleven major Italian cities, were downscaled to obtain high spatial resolution (100 m) daytime and night-time land surface temperatures (LST). LST was estimated pixel-wise by applying two statistical model approaches: 1) the Linear Regression Model (LRM); 2) the Generalized Additive Model (GAM). Total and elderly population density data were extracted from the Joint Research Centre population grid (100 m) from the 2001 census (Eurostat source), and processed together using "Crichton's Risk Triangle" hazard-risk methodology for obtaining a Heat-related Elderly Risk Index (HERI)., Results: The GAM procedure allowed for improved daytime and night-time LST estimations compared to the LRM approach. High-resolution maps of daytime and night-time HERI levels were developed for inland and coastal cities. Urban areas with the hazardous HERI level (very high risk) were not necessarily characterized by the highest temperatures. The hazardous HERI level was generally localized to encompass the city-centre in inland cities and the inner area in coastal cities. The two most dangerous HERI levels were greater in the coastal rather than inland cities., Conclusions: This study shows the great potential of combining geospatial technologies and spatial demographic characteristics within a simple and flexible framework in order to provide high-resolution urban mapping of daytime and night-time HERI. In this way, potential areas for intervention are immediately identified with up-to-street level details. This information could support public health operators and facilitate coordination for heat-related emergencies.

Khorasan wheat is an ancient grain with previously reported health benefits in clinically healthy subjects. The aim of this study was to examine whether a replacement diet, thereby substituting all other cereal grains, with products made with organic khorasan wheat could provide additive protective effects in reducing lipid, oxidative and inflammatory risk factors, in patients with Acute Coronary Syndromes (ACS) in comparison to a similar replacement diet using products made from organic modern wheat. A randomized double-blinded crossover trial with two intervention phases was conducted on 22 ACS patients (9 F; 13 M). The patients were assigned to consume products (bread, pasta, biscuits and crackers) made either from organic semi-whole khorasan wheat or organic semi-whole control wheat for eight weeks in a random order. On average, patients ingested 62.0 g dry weight (DW) day-1 khorasan or control semolina; and 140.5 g DW day-1 khorasan or control flour, respectively. An eight-week washout period was implemented between the respective interventions. Blood analyses were performed both at the beginning and end of each intervention phase; thereby permitting a comparison of both the khorasan and control intervention phases, respectively, on circulatory risk factors for the same patient. Consumption of products made with khorasan wheat resulted in a significant amelioration in total cholesterol (-6.8%), low-density lipoprotein cholesterol (LDL-C) (-8.1%) glucose (-8%) and insulin (-24.6%) from baseline levels, independently of age, sex, traditional risk factors, medication and diet quality. Moreover, there was a significant reduction in reactive oxygen species (ROS), lipoperoxidation of circulating monocytes and lymphocytes, as well as in the levels of Tumor Necrosis Factor-alpha. No significant differences from baseline in the same patients were observed after the conventional control wheat intervention phase. The present results suggest that a replacement diet with cereal products made from organic khorasan wheat provides additional protection in patients with ACS. Circulating cardiovascular risk factors, including lipid parameters, and markers of both oxidative stress and inflammatory status, were reduced, irrespective of the number and combination of medicinal therapies with proven efficacy in secondary prevention.

No datum is so far available on the relation between age and the acute glucose response to stress in women with ST-elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention (PCI).We evaluated the age-related differences in the acute glucose response in 373 STEMI women submitted to PCI. The oldest women, when compared to the other age subgroups, showed the higher admission and peak glycemia (P < 0.001 and P < 0.001, respectively) in the lack of differences in insulin, C-peptide, hemoglobin-glycated values and discharge glycemia values. At logistic regression analysis, the following variables were independent predictors of in-Intensive Cardiac Care Unit mortality: age (1-year step) [odds ratio 1.09, 96% confidence interval (CI) 1.04-1.15, P = 0.001], admission glycemia (1g/l step) (odds ratio 2.05, 96% CI 1.35-3.12, P < 0.001). At Cox regression analysis the following variables were associated with 1-year mortality (when adjusted for discharge glycemia): age (1-year step) (hazard ratio 1.13, 95% CI 1.04-1.22, P = 0.005), estimated glomerular filtration rate (1 g/l step) (hazard ratio 0.93, 95% CI 0.90-0.96, P < 0.001).Age affects the acute glucose response to myocardial injury since older women showed the higher admission glucose values and the poorer in-hospital glucose control, in the lack of differences of insulin-resistance incidence. Glucose values were independent predictors of in-hospital mortality, but were not related to long-term survival.

Aims and Background: Radiobiological and technical considerations have traditionally limited the role of radiation therapy in the context of primary and secondary cardiac malignancies. Stereotactic body radiotherapy (SBRT) is a promising modality for the delivery of focused high-dose radiation with ablative potential to complex targets such as small, deep-seated, moving lesions, allowing also for re-irradiation., Methods: Between January 2013 and October 2013, 3 patients underwent SBRT for cardiac lesions: 2 patients had recurrent, previously irradiated cardiac angiosarcomas (PCA) and 1 patient had a cardiac metastasis from melanoma. They were treated with fiducial-guided robotic radiotherapy with CyberKnife. As for dose prescription, 24 Gy in 3 fractions (80% isodose) and 30 Gy in 5 fractions (80% isodose) were administered to the recurrent PCAs and cardiac metastasis, respectively., Results: At 2 months after SBRT, cardiac MRI showed a partial response in the patients treated for recurrent PCA while the cardiac metastasis remained stable. In all cases, absence of local progression was subsequently confirmed by contrast-enhanced cardiac MRI after 6 months, without any evidence of treatment-related side effects., Conclusions: Fiducial-guided SBRT proved to be feasible and effective in preventing local disease progression in selected patients with cardiac malignancies.

Background: By examining the genotype calls generated by the 1000 Genomes Project we discovered that the human reference genome GRCh37 contains almost 20,000 loci in which the reference allele has never been observed in healthy individuals and around 70,000 loci in which it has been observed only in the heterozygous state., Results: We show that a large fraction of this rare reference allele (RRA) loci belongs to coding, functional and regulatory elements of the genome and could be linked to rare Mendelian disorders as well as cancer. We also demonstrate that classical germline and somatic variant calling tools are not capable to recognize the rare allele when present in these loci. To overcome such limitations, we developed a novel tool, named RAREVATOR, that is able to identify and call the rare allele in these genomic positions. By using a small cancer dataset we compared our tool with two state-of-the-art callers and we found that RAREVATOR identified more than 1,500 germline and 22 somatic RRA variants missed by the two methods and which belong to significantly mutated pathways., Conclusions: These results show that, to date, the investigation of around 100,000 loci of the human genome has been missed by re-sequencing experiments based on the GRCh37 assembly and that our tool can fill the gap left by other methods. Moreover, the investigation of the latest version of the human reference genome, GRCh38, showed that although the GRC corrected almost all insertions and a small part of SNVs and deletions, a large number of functionally relevant RRAs still remain unchanged. For this reason, also future resequencing experiments, based on GRCh38, will benefit from RAREVATOR analysis results. RAREVATOR is freely available at http://sourceforge.net/projects/rarevator .

The aim of the study was to evaluate the association between circulating (CPCs) and endothelial (EPCs) progenitor cells and left ventricular (LV) remodeling in chronic heart failure (HF). 85 HF patients, ranging 29-89 years, 83.5% males, 45.9% ischemic, NYHA functional class II-IV, with a LV ejection fraction ≤40% were studied. LV ejection fraction, LV end-diastolic and end-systolic (LVESV) volumes, LV mass and tricuspid annular plane systolic excursion (TAPSE) were evaluated, and, when indicated, indexed for body surface area (BSA). CPCs and EPCs number was assessed using flow cytometry. CPCs were defined as CD34+, CD133+ and CD34+/CD133+. EPCs, identified through their expression of KDR, were defined as CD34+/KDR+, CD133+/KDR+ and CD34+/CD133+/KDR+. All EPCs were negatively related to LVESV/BSA (r = -0.24, p = 0.02 for all EPC's populations), and to LVmass/BSA (CD34+KDR+; r = -0.30, p = 0.005; CD133+KDR+; r = -0.31, p = 0.004; CD34+CD133+KDR+; r = -0.29, p = 0.007). No differences in EPCs levels in relation to cardiovascular risk factors, medications, etiology, age or gender were observed. CPCs number was higher in women, and lower in ischemic patients. In logistic regression analyses, the low EPCs' number was associated with an increased likelihood of abnormal LVmass/BSA. CPCs proved to be higher and EPCs lower in patients with severely abnormal LVmass/BSA (gr/m(2), ≥122 in women and ≥149 in men). Our results suggest a correlation between LV remodeling and progenitor cells. This is noteworthy considering that it has been suggested that bone marrow-derived EPCs participate in cardiac regeneration and function recovery in the setting of progressive HF.

Objectives: To clarify the impact of multiple (covering the same population, intervention, control, and outcomes) systematic reviews (SRs) on interventions for myocardial infarction (MI)., Study Design and Setting: Clinical Evidence (BMJ Group) sections and related search strategies regarding MI were used to identify multiple SRs published between 1997 and 2007. Multiple SRs were classified as discordant if they featured conflicting results or interpretation of them., Results: Thirty-six SRs (23.5% of 153 on the treatment or prevention of MI) were classified as multiple and grouped in 16 clusters [ie, at least two SRs with the same PICO (population, condition/disease, intervention, control) and at least one common outcome] exploring angioplasty, angiotensin-converting enzyme inhibitors, anticoagulants, antiplatelets, β-blockers, and stents. Complete agreement on statistically significant differences between interventions was found in 7 of 10 clusters with a shared composite outcome. Agreement was reduced when single outcomes were considered. Despite substantial variation and limited agreement in reporting of major outcomes, SRs agreed in their conclusions on the superiority of either the intervention or control in 14 of 16 clusters. Sources of minor discrepancies were found in terms of study and outcome selection, subgroup analyses, and interpretation of findings., Conclusion: Multiple SRs agreed in their qualitative conclusions but not on reporting and on analyses of hard outcomes. Discordance on significance of treatment effects was due to a combination of variation in design with inclusion of different studies and lack of precision for single hard outcomes compared with a composite outcome. Such inconsistencies among SRs could potentially slow the translation of SRs' results to clinical and public health decision making and suggest the need for a broader methodological and clinical agreement on their design., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: The choice of imaging techniques in patients with suspected coronary artery disease (CAD) varies between countries, regions, and hospitals. This prospective, multicenter, comparative effectiveness study was designed to assess the relative accuracy of commonly used imaging techniques for identifying patients with significant CAD., Methods and Results: A total of 475 patients with stable chest pain and intermediate likelihood of CAD underwent coronary computed tomographic angiography and stress myocardial perfusion imaging by single photon emission computed tomography or positron emission tomography, and ventricular wall motion imaging by stress echocardiography or cardiac magnetic resonance. If ≥1 test was abnormal, patients underwent invasive coronary angiography. Significant CAD was defined by invasive coronary angiography as >50% stenosis of the left main stem, >70% stenosis in a major coronary vessel, or 30% to 70% stenosis with fractional flow reserve ≤0.8. Significant CAD was present in 29% of patients. In a patient-based analysis, coronary computed tomographic angiography had the highest diagnostic accuracy, the area under the receiver operating characteristics curve being 0.91 (95% confidence interval, 0.88-0.94), sensitivity being 91%, and specificity being 92%. Myocardial perfusion imaging had good diagnostic accuracy (area under the curve, 0.74; confidence interval, 0.69-0.78), sensitivity 74%, and specificity 73%. Wall motion imaging had similar accuracy (area under the curve, 0.70; confidence interval, 0.65-0.75) but lower sensitivity (49%, P<0.001) and higher specificity (92%, P<0.001). The diagnostic accuracy of myocardial perfusion imaging and wall motion imaging were lower than that of coronary computed tomographic angiography (P<0.001)., Conclusions: In a multicenter European population of patients with stable chest pain and low prevalence of CAD, coronary computed tomographic angiography is more accurate than noninvasive functional testing for detecting significant CAD defined invasively., Clinical Trial Registration Url: http://www.clinicaltrials.gov. Unique identifier: NCT00979199., (© 2015 American Heart Association, Inc.)

Aims: Mild renal impairment (estimated GFR 60-89 ml/min/1.73 m(2)) is a strong independent risk factor for mortality in ST-elevation myocardial infarction (STEMI), and is submitted to mechanical revascularization. Patients with renal impairment have decreased excretion of uric acid (UA) and they are thus particularly prone to have elevated serum UA concentrations. This study was aimed at assessing the association between increased UA and mortality in STEMI patients with mild renal impairment., Methods: We prospectively assessed, in 578 STEMI patients with mild renal impairment, whether elevated UA levels are associated with increased mortality both in the short term and in the long term., Results: Patients in the highest UA tertile showed a higher incidence of Killip class III-IV (p = 0.003) and lower values of ejection fraction (EF) (p < 0.001). Lower values for estimated glomerular filtration rate (eGFR) at admission, nadir, and discharge were detected in the highest UA tertile, together with the highest values of peak troponin I (Tn I) (p = 0.002), and NT-proBrain Natriuretic Peptide [NT-proBNP] (p < 0.001). No difference was found in mortality rates (both during their stay in the intensive cardiac care unit [ICCU], and at the 1-year post-discharge follow-up) among the UA tertiles., Conclusions: The UA levels seem to serve as markers of the severity of coronary artery disease, since they identify a subset of patients characterized by an advanced age, more hemodynamic derangement, and reduced renal function. However, neither short nor long-term mortality was affected.

Background: Few studies have analyzed the clinical and echocardiographic differences between light-chain (AL) and transthyretin (TTR) amyloidosis., Hypothesis: The aim of the present research was to compare, in a real-world setting, the clinical and echocardiographic profiles of these kinds of amyloidosis, at the time of diagnosis, using new-generation echocardiography., Methods: Seventy-nine patients with AL and 48 patients with TTR amyloidosis were studied., Results: According to the criterion of mean left ventricular (LV) thickness >12 mm, 45 AL (C-AL) and all TTR patients had cardiac amyloidotic involvement, whereas 34 AL patients did not. TTR patients had increased right ventricular (RV) and LV chambers with increased RV and LV wall thickness and reduced LV ejection fraction and fractional shortening. Furthermore, TTR patients showed lower N-terminal pro Brain Natriuretic Peptide concentrations and New York Heart Association functional class when compared with C-AL., Conclusions: Our data show that at time of first diagnosis, TTR patients have a more advanced amyloidotic involvement of the heart, despite less severe symptoms and biohumoral signs of heart failure. We can hypothesize that we observed different diseases at different stages. In fact, AL amyloidosis is a multiorgan disease with quick progression rate, that becomes rapidly symptomatic, whereas TTR amyloidosis might have a slow progression rate and might remain poorly symptomatic for a greater amount of time., (© 2015 Wiley Periodicals, Inc.)

Background: The novel exercise computer-assisted high-frequency QRS analysis (HF/QRS) has demonstrated improved sensitivity and specificity over the conventional ST/electrocardiogram-segment analysis (ST/ECG) in the detection of myocardial ischemia. The aim of the present study was to compare the diagnostic value of the validated exercise echocardiography (ex-Echo) with the novel exercise ECG (ex-ECG) including HF/QRS and ST/ECG analysis., Methods: A prospective cohort study was conducted in the emergency department of a tertiary care teaching Hospital. Patients with chest pain (CP), normal resting ECGs, troponins, and echocardiography, labeled as "intermediate-risk" for adverse coronary events, underwent the novel ex-ECG and ex-Echo. An ST-segment depression of at least 2 mV or at least 1 mV when associated with CP was considered as an index of ischemia, as well as a decrease of at least 50% in HF/QRS intensity, or new wall motion abnormalities on ex-Echo. Exclusion criteria were QRS duration of at least 120 milliseconds, poor echo-acoustic window, and inability to exercise. Patients were followed up to 3 months. The end point was the composite of coronary stenoses of 50% or greater at angiography or acute coronary syndrome, revascularization, and cardiovascular death on the 3-month follow-up., Results: Of 188 patients enrolled, 18 achieved the end point. The novel ex-ECG and ex-Echo showed comparable negative predictive value (97% vs 96%; P = .930); however, sensitivity was 83% vs 61%, respectively (P = .612), and specificity was 64% vs 92%, respectively,(P = .026). The areas on receiver operating characteristic analysis were comparable (ex-ECG: 0.734 [95% confidence interval, or CI, 0.62-0.85] vs ex-Echo: 0.767 [CI, 0.63-0.91]; C statistic, P = .167). On multivariate analysis, both ex-ECG (hazard ratio, 5; CI, 1-20; P = .017) and ex-Echo (HR, 12; CI, 4-40; P < .001) were predictors of the end point., Conclusions: In intermediate-risk CP patients, the novel ex-ECG including HF/QRS added to ST/ECG analysis was a valuable diagnostic tool and might be proposed to avoid additional imaging. However, the novel test needs additional study before it can be recommended as a replacement for current techniques., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: The effect of thrombus aspiration on mortality is still controversial, with results which are often inconsistent in different randomized trials, real world registries and different follow-up duration. The aim of this analysis was to assess the effect on 30-day and 1-year mortality of thrombus aspiration during primary percutaneous coronary intervention (pPCI) for ST-elevation myocardial infarction (STEMI) compared with conventional PCI., Methods: We used data from all the consecutive STEMI patients treated either with conventional PCI or thrombus aspiration between January 1, 2004 and January 1, 2012. Propensity matching score was calculated on the basis of several baseline and procedural characteristics in order to predict the probability for each patient of having been treated with thrombus aspiration. This propensity score analysis was used in order to select a cohort of patients treated with thrombus aspiration matched one-to-one with patients treated with conventional PCI., Results: In total, 744 (53.1%) patients out of 1,400 enrolled were treated with thrombus aspiration. In the matched cohort, at 30-day follow-up 6.3% of patients in the conventional PCI group died compared to 4.7% in the thrombus aspiration group. The unadjusted hazard ratio (HR) for 30-day mortality was 1.01 (95% CI 0.33-3.14, p = 0.985). In the same cohort, 10.7% of patients died at 1-year in the conventional PCI group compared to 5.2% in the thrombus aspiration group. The 1-year unadjusted hazard ratio for mortality was 0.47 (95% CI 0.25-0.90, p = 0.025). The HR changed and was no longer significant after adjustment for differences in the use of glycoprotein (GP) IIb/IIIa inhibitors, lesion pre-dilatation and pre-procedural TIMI flow: 0.71 (95% CI 0.36-1.39, p = 0.322)., Conclusions: Thrombus aspiration does not influence 30-day mortality, however it is associa­ted with 1-year survival benefit. GP IIb/IIIa inhibitors and thrombus aspiration may have an important synergistic role in leading to this long-term benefit.

Identification of patients with acute ischaemic stroke who could most benefit from arterial recanalization after endovascular treatment remains an unsettled issue. Although several classifications of collateral circulation have been proposed, the clinical role of collaterals is still debated. We evaluated the effect of the collateral circulation in relation to recanalization as a predictor of clinical outcome. Data were prospectively collected from 103 patients consecutively treated for proximal middle cerebral or internal carotid artery occlusion. The collateral circulation was evaluated with a novel semiquantitative-qualitative score, the Careggi collateral score (CCS), in six grades. Both CCS and recanalization grades (TICI) were analysed in relation to clinical outcome. A statistical analysis was performed to evaluate the effect of interaction between recanalization and collateral circulation on clinical outcome. Out of the 103 patients, 37 (36.3%) had poor collaterals, and 65 (63.7%) had good collaterals. Patients with good collaterals had lower basal National Institute of Health Stroke Scale (NIHSS), more distal occlusion, smaller lesions at 24h CT scan and better functional outcome. After multivariate analysis, the interaction between recanalization and collateral grades was significantly stronger as a predictor of good outcome (OR 6.87, 95% CI 2.11-22.31) or death (OR 4.66, 95%CI 1.48-14.73) compared to the effect of the single variables. Collaterals showed an effect of interaction with the recanalization grade in determining a favourable clinical outcome. Assessment of the collateral circulation might help predict clinical results after recanalization in patients undergoing endovascular treatment for acute ischaemic stroke.

Objective: To update previous meta-analyses of cohort studies that investigated the association between the Mediterranean diet and health status and to utilize data coming from all of the cohort studies for proposing a literature-based adherence score to the Mediterranean diet., Design: We conducted a comprehensive literature search through all electronic databases up to June 2013., Setting: Cohort prospective studies investigating adherence to the Mediterranean diet and health outcomes. Cut-off values of food groups used to compute the adherence score were obtained., Subjects: The updated search was performed in an overall population of 4 172 412 subjects, with eighteen recent studies that were not present in the previous meta-analyses., Results: A 2-point increase in adherence score to the Mediterranean diet was reported to determine an 8 % reduction of overall mortality (relative risk = 0·92; 95 % CI 0·91, 0·93), a 10 % reduced risk of CVD (relative risk = 0·90; 95 % CI 0·87, 0·92) and a 4 % reduction of neoplastic disease (relative risk = 0·96; 95 % CI 0·95, 0·97). We utilized data coming from all cohort studies available in the literature for proposing a literature-based adherence score. Such a score ranges from 0 (minimal adherence) to 18 (maximal adherence) points and includes three different categories of consumption for each food group composing the Mediterranean diet., Conclusions: The Mediterranean diet was found to be a healthy dietary pattern in terms of morbidity and mortality. By using data from the cohort studies we proposed a literature-based adherence score that can represent an easy tool for the estimation of adherence to the Mediterranean diet also at the individual level.

Donor scarcity and the increased need for organ transplantation has prompted the development of an alternative source of donors to the more conventional brain dead donor. While in a Beating-Heart donor, abdominal and intrathoracic organs are perfused, in a non-beating heart donor (NHBD, or DCD), perfusion should be maintained, after confirmation of death, by means of ECMO and inflation of intra-aortic balloon accordingly to the localization of the organs that should be transplanted. In this setting, ECMO allows selective perfusion of the organs which should be transplanted ("compartmental ECMO"). The present review is aimed at summarizing the rationale for ECMO use in organ donation in DCD and the available evidence on this topic, as well as available evidence (in clinical studies) on normothermic organ preservation using ECMO in adults. Despite the fact that available studies suffer from methodological limitations (small cohorts, retrospective analysis, not always comparative), they all reach the same conclusion: the concept of extracorporeal support with oxygenation in DCD seems very promising since it has been reported to increase the available organ supply by approximately 20% to 25%2 by increasing the number of donors by approximately 33%. Centres with ECMO facilities should implement local programmes for donation after cardiac death (both in the emergency department and intensive care) using ECMO taking into account that this technique has been proven to increase donor pool.