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Background Incidence and long-term clinical consequences of prosthesis-patient mismatch (PPM) after transcatheter aortic valve replacement (TAVR) are still unclear. Methods We enrolled 710 consecutive patients who underwent TAVR. PPM was defined as absent if the index orifice area (iEOA) was >0.85 cm2/m2, moderate if the iEOA was between 0.65 and 0.85 cm2/m2 or severe if the iEOA was Results Among the 566 patients fulfilling the study criteria, the distribution of PPM was as follows: 50.5% none (n = 286), 43% moderate PPM (n = 243) and 6.5% severe PPM (n = 37). At 5-year follow-up, patients with severe PPM had a significantly higher incidence of the combined endpoint of cardiovascular death, acute myocardial infarction and stroke (p = .025) compared with the other patients. After adjusting the results for possible confounders, severe PPM remained an independent predictor of long-term adverse outcome (HR: 2.46; 95% Confidence Interval: 1.10–5.53). The independent predictors of severe PPM were valve-in-valve procedure and body mass index. Balloon-expandable valves were not associated with higher rates of severe PPM in comparison with self-expandable valves (8% vs. 5%, respectively, p = .245). Conclusions In our study severe PPM emerged as a risk factor for long-term major adverse cardiac and cerebrovascular events.

This study sought to investigate the impact of elective, uncomplicated target lesion revascularization (TLR) on long-term cardiac mortality after percutaneous coronary intervention (PCI) of unprotected left main coronary artery (ULMCA) disease. Consecutive patients undergoing PCI for ULMCA disease between January 2003 and December 2015 in 1 interventional center in Northern Italy were included. Patients presenting with cardiogenic shock, ST-segment elevation myocardial infarction (MI), as well as those undergoing urgent or complicated TLR were excluded. The primary endpoint of the study was cardiac mortality. Among the 418 patients fulfilling the study criteria, 79 (18.46%) underwent elective, uncomplicated TLR. After a median follow-up of 5.5 years, there were 23 cardiac deaths among patients undergoing elective, uncomplicated TLR versus 50 in patients not undergoing TLR. After adjusting for possible confounders, TLR was an independent predictor of cardiac mortality (Hazard ratio [HZ] = 1.92, 95% confidence interval [CI]: 1.05 to 3.49; p = 0.03). Patients undergoing TLR had also significantly higher rates of the composite of cardiac death, MI and stroke compared with the no TLR group (adjusted HR = 1.76, 95% CI 1.14 to 2.72). In conclusion, elective, uncomplicated TLR after PCI of ULMCA disease is associated with increased risk of long-term cardiac mortality. Reducing the risk of TLR after PCI of ULMCA disease may potentially improve the survival of these patients.

Little evidence is available regarding the risk of hepatic decompensation (HD) after direct-acting antivirals (DAAs) in patients with advanced chronic liver disease. Our aim was to assess the risk of decompensation and the prognostic role of noninvasive tests, such as liver (LSM) and spleen (SSM) stiffness measurements, in the prediction of decompensation after sustained virologic response (SVR) by DAAs.A cohort study involving 146 cirrhotic patients treated with DAAs in our tertiary center with LSM and SSM available both before and six months after treatment (SVR24). A historical cohort of 92 consecutive cirrhotic patients with active HCV was used as a control group. A propensity score inverse probability weighting method was used to account for differences between the groups. Time-dependent models for the prediction of decompensation were applied to account for changes in noninvasive tests after therapy.The decompensation incidence in the DAA cohort was 7.07 (4.56-10.96) per 100 person-years (PYs), which was significantly lower than in the active HCV cohort. The DAA therapy was an independent protective factor for HD development (SHR: 0.071, 95 %-CI: 0.015-0.332). SSM ≥ 54 kPa was independently associated with decompensation despite SVR achievement (SHR: 4.169, 95 %-CI: 1.050-16.559), alongside with a history of decompensation (SHR: 7.956, 95 %-CI: 2.556-24.762). SSM reduction 10 % also predicted the risk of decompensation after SVR24.The risk of decompensation was markedly reduced after DAA therapy, but it was not eliminated. Paired SSM values stratified the risk of decompensation after SVR better than other noninvasive tests.ZIEL: Über das Risiko einer hepatischen Dekompensation (HD) nach direkt antiviral wirksamen Substanzen (DAA) bei Patienten mit fortgeschrittener chronischer Lebererkrankung gibt es nur wenig Evidenz. Unser Ziel war es, das Risiko einer Dekompensation und den prognostischen Wert nichtinvasiver Tests wie Messungen der Lebersteifigkeit (LSM) und Milzsteifigkeit (SSM) zur Vorhersage einer Dekompensation nach anhaltendem virologischem Ansprechen (SVR) unter DAA zu bewerten.Kohortenstudie mit 146 Zirrhose-Patienten, die in unserem Tertiärzentrum mit DAAs behandelt wurden, wobei LSM und SSM sowohl vor als auch 6 Monate nach der Behandlung verfügbar waren (SVR24). Eine historische Kohorte von 92 konsekutiven zirrhotischen Patienten mit aktiver HCV wurde als Kontrollgruppe verwendet. Um die Unterschiede zwischen den Gruppen zu berücksichtigen, wurde die Propensity-Score-Methode („inverse probability weighting“) verwendet. Zeitabhängige Modelle zur Prädiktion der Dekompensation wurden angewandt, um Veränderungen in den nichtinvasiven Tests nach Therapie zu berücksichtigen.Die Dekompensations-Inzidenz in der DAA-Kohorte betrug 7,07 (4,56–10,96) pro 100 Personenjahre (PYs), was signifikant niedriger war als in der aktiven HCV-Kohorte. Die DAA-Therapie war ein unabhängiger protektiver Faktor für die Entwicklung einer HD (SHR: 0,071; 95 %-KI 0,015–0,332). SSM ≥ 54kPa war trotz erfolgreichem SVR unabhängig mit Dekompensation assoziiert (SHR: 4,169; 95 %-KI 1,050–16,559), zusammen mit früher aufgetretener Dekompensation (SHR: 7,956; 95 %-KI 2,556–24,762). Eine SSM-Reduktion 10 % sagte auch das Risiko einer Dekompensation nach SVR24 voraus.Das Risiko einer Dekompensation war nach DAA-Therapie deutlich reduziert, aber nicht eliminiert. Gepaarte SSM-Werte stratifizierten das Risiko einer Dekompensation nach SVR besser als andere nichtinvasive Tests.

Background To assess whether coronary bypass (CABG) or stenting reduce the risk of mortality and myocardial infarction (MI) compared with optimal medical therapy (OMT) in stable coronary artery disease (CAD). Methods We performed a systematic review and network meta-analysis of contemporary randomized controlled trials comparing OMT, CABG and different stent types in stable CAD. All-comer trials were included if the rate of patients with acute myocardial infarction (AMI) was≤20%. Endpoints were all-cause mortality and MI. Results Ninety-seven trials including 75,754 patients were analyzed at a weighted mean follow up of 42.5 months. Compared to OMT, CABG was associated with a lower risk of death (OR = 0.84; 95%CI:0.71–0.97). After exclusion of trials in left main and/or multivessel disease(LM/MVD) this benefit was not statistically significant (OR = 0.89; 95%CI:0.74–1.06). CABG was associated with a lower risk of MI (OR = 0.67;95%CI: 0.49–0.91) showing, however, a certain degree of inconsistency (p=0.10). None of the stent types included was associated with a lower risk of death. However, durable-polymer-CoCr-everolimus-eluting stent, by mixed evidence, after exclusion of either LM/MVD (OR = 0.73;95%CI: 0.54–0.98) or all-comer/post-MI trials (OR = 0.62;95%CI:0.39–0.98) was associated with a lower risk of MI than OMT. Similar findings, by indirect evidence, were confirmed for bio-absorbable-polymer-CoCr-sirolimus eluting stent (LMV/MVD trials excluded OR = 0.46; 95%CI = 0.29–0.74, all-comer/post-MI trials excluded: OR = 0.41;95%CI:0.22–0.79). Conclusions In stable CAD, CABG reduces the risk of mortality and MI compared to OMT, especially in patients with higher extent of CAD. Our study suggests that some of second and latest-generation drug-eluting stents may reduce the risk of MI. Future research should confirm these latter findings.

Objectives The aim of this study was to investigate the safety and efficacy of coronary protection by preventive coronary wiring and stenting across the coronary ostia in patients at high risk for coronary obstruction after transcatheter aortic valve replacement (TAVR). Background Coronary obstruction following TAVR is a life-threatening complication with high procedural and short-term mortality. Methods Data were collected retrospectively from a multicenter international registry between April 2011 and February 2019. Results Among 236 patients undergoing coronary protection with preventive coronary wiring, 143 had eventually stents implanted across the coronary ostia after valve deployment. At 3-year follow-up, rates of cardiac death were 7.8% in patients receiving stents and 15.7% in those not receiving stents (adjusted hazard ratio: 0.42; 95% confidence interval: 0.14 to 1.28; p = 0.13). There were 2 definite stent thromboses (0.9%) in patients receiving stents, both occurring after TAVR in “valve-in-valve” procedures. In patients not receiving stents, there were 4 delayed coronary occlusions (DCOs) (4.3%), occurring from 5 min to 6 h after wire removal. Three cases occurred in valve-in-valve procedures and 1 in a native aortic valve procedure. Distance between the virtual transcatheter valve and the protected coronary ostia Conclusions In patients undergoing TAVR at high risk for coronary obstruction, preventive stent implantation across the coronary ostia is associated with good mid-term survival rates and low rates of stent thrombosis. Patients undergoing coronary protection with wire only have a considerable risk for DCO.

Background The prognostic role of spontaneous portosystemic shunts (SPSS) has been poorly investigated. Aims To evaluate the impact of the presence of SPSS, as well as their characteristics, on the risk of decompensation. Methods This is a retrospective cohort study of 235 advanced chronic liver disease (ACLD) patients with available imaging examination, transient elastography, and upper endoscopy. ACLD was defined as liver stiffness measurement (LSM) >10 kPa. Competitive risk analyses were performed to identify the factors associated with the main outcome. Results SPSS were reported in 141 (60%) of the patients. Non-viral etiology was independently associated with SPSS presence [Odds-Ratio (OR): 2.743;95%-Interval-of-Confidence (IC):1.129–6.664]. During a follow-up of 37 (20–63) months, SPSS were found predictors of any decompensation type [Subhazard Ratio (SHR):2.264; 95%-IC:1.259–4.071], independently from a history of decompensation or high-risk-varices presence. The risk of complications was higher in patients with large (SHR: 3.775; 95%-IC: 2.016–7.070) and multiple (SHR:3.832; 95%-IC: 2.004–7.330) shunts, and in those with gastrorenal shunts (SHR:2.636; 95%-IC:1.521–4.569). Conclusions The presence, size, and number of SPSS predict not only the risk of hepatic encephalopathy but that of any type of decompensation across all stages of cirrhosis. Future studies should explore the possibility of treating shunts to prevent decompensation.

Background and Aims: Cirrhotic patients with hepatitis C virus (HCV) infection remain at risk of developing hepatocellular carcinoma (HCC) even after the sustained virologic response (SVR). We aimed to evaluate whether the IL28 (rs12979860) single nucleotide polymorphism (SNP) may constitute a predisposing genetic factor and to identify the SVR patients at risk of HCC. Methods: Two hundred patients undergoing DAAs treatment for chronic hepatitis C with advanced fibrosis (F3- F4) were consecutively enrolled. Besides normal routine laboratory testing for HCV, patients’ sera were evaluated also for retinol, retinol-binding protein 4 and the following SNPs: PNPLA3 (rs738409), TM6SF2 (rs58542926), MBOAT7 (rs641738), IL28B (rs12979860), TIMP-1 (rs4898), TIMP-2 (rs8179090), NF-kB promoter (rs28362491). Statistical analyses were conducted using Stata/SE 14.2 statistical software (Stata Corp, College Station, TX). Results: Almost all patients (197/200) obtained SVR24. Seventeen patients had a previous history of treated HCC before DAAs. Six patients developed HCC recurrence and five patients developed de novo HCC after a mean period of 18 months since EOT. All these patients had SVR. A significant association between IL28B – TT genotype and HCC development after DAAs therapy was observed (OR 4.728, CI 95% 1.222 – 18.297, p=0.024). Conclusion: IL28B rs12979860 polymorphism was significantly associated with HCC development after DAAs. Assessment of this SNP may better identify patients at risk of developing HCC after treatment. Further prospective studies are required to confirm these hypotheses.

Purpose: Intrapartum antibiotic prophylaxis (IAP) prevents group B streptococcus (GBS) early-onset disease (EOD). No European study evaluates the relative impact of risk factors (RFs) for EOD after...

Background & Aims Hepatocellular carcinoma (HCC) is a frequent complication of liver disease. When feasible, hepatic resection is the first-choice therapy. However, tumor recurrence complicates at least 2/3 hepatic resections at 5 years. Early recurrences are mainly tumor or treatment-related, but predictors of late recurrences are undefined. We aimed to evaluate the factors related to HCC recurrence after curative resection, with liver and spleen stiffness measurement (LSM and SSM) as markers of severity and duration of the underlying liver disease. Methods We enrolled patients with chronic liver disease and primary HCC suitable for hepatic resection. We followed up patients for at least 30 months or until HCC recurrence. We performed uni- and multivariate analyses to evaluate the predictive role of tumor characteristics, laboratory data, LSM and SSM for both early and late recurrence of HCC. Results We prospectively enrolled 175 patients. Early HCC recurrence at multivariate analysis was associated with viral etiology, HCC grading (3 or 4), resection margins Conclusions SSM seems to be the only predictor of late HCC recurrence, since it is directly correlated with the degree of liver disease and portal hypertension, both of which are involved in carcinogenesis. Lay summary The main result of this study is that spleen stiffness measurement, evaluated by transient elastography, seems to be the only predictor of the late recurrence of hepatocellular carcinoma, defined as recurrence after 24 months from liver resection. Indeed, spleen stiffness measurement is directly correlated with the degree of liver disease and portal hypertension, which are both involved in carcinogenesis.

Background isolated distal deep vein thromboses (IDDVT) are frequent; however, their optimal management is still controversial. Methods we performed a retrospective study on inpatients undergoing ultrasound for suspected deep vein thrombosis (DVT) or with a particular risk profile, during 2016. The study was aimed to assess the frequency of proximal deep vein thromboses (PDVT) and IDDVT; to evaluate therapeutic management and identify variables associated with early outcomes and mortality among IDDVT patients; to compare all-causes mortality between subjects with PDVT and IDDVT. Results among 21594 patients hospitalized in the study period 251 IDDVT and 149 PDVT were diagnosed; the frequency was 1.2 % and 0.7% respectively. 19% of IDDVT patients died compared to 25,5% of PDVT subjects (OR 0.72; 95% CI 0.44-1.17; p 0.19). In IDDVT patients, age ≥ 80, cancer and intracranial bleeding increased the risk of death (OR 2; 95% CI 1.07-3.75, p 0.001; OR 8.47; 95% CI 3.28-21.88, p 0.0000003; OR 2.33; 95% CI 1.18-4.58, p 0.0003). A significant association between intracranial hemorrhage and both proximal extension by using the Fisher's exact test (p 0.031; OR 16.11; 95% CI 0.80-321.2), and composite of propagation to popliteal or to other calf veins (OR 8.28, 95% CI 2.07-33 p 0.001) was observed. Standard anticoagulation significantly reduced the composite of propagation to popliteal or to other calf veins (OR 0.07; 95% CI 0.009-0.61, p 0.007), and all-causes mortality (OR 0.37; 95% CI 0.17-0.8; p 0.02), without a significant increase of bleeding. Conclusions among inpatients, IDDVT exceeded 60% of DVT. Mortality was not significantly different between IDDVT and PDVT subjects. Intracranial bleeding significantly increased the risk of propagation and death. Although standard anticoagulation decreased both these complications, further targeted studies are needed.

Introduction: Coarctation of the aorta (CoA) is common and can lead to neonatal emergency. Despite its burden, antenatal detection of this condition remains inaccurate. Objective: To evaluate the diagnostic performance of fetal echocardiography and to design a scoring system for risk stratification of CoA in suspected cases. Design: A retrospective cohort study. Setting: S. Orsola Hospital, Bologna, Italy. Population: About 140 fetuses referred for suspected CoA to our tertiary center in a 9-year period. Methods: The following parameters were systematically obtained at fetal echocardiography: ventricular disproportion, great vessels asymmetry, transverse aortic arch hypoplasia, flow turbulence, and Z-scores of the ascending aorta and of the aortic isthmus. Associated anomalies were recorded, if present. When CoA was not confirmed at birth, neonates were followed up for 12 months to identify also a tardive onset of this condition. Main outcome measures: The primary outcome was the presence of COA after birth. Results: 108 fetuses were eligible for the purpose of the study. CoA was confirmed postnatally in 55 neonates (50.9%). Arch hypoplasia yielded the highest correlation with CoA. The affected neonates presented also significantly lower Z scores of the ascending aorta and of the aortic isthmus. Earlier gestational age at referral was positively correlated with neonatal CoA. An odds ratio-based multiparametric model was designed to build a scoring system (AUC 0.89). Conclusion: In our cohort, no single ultrasound parameter was sufficiently accurate to predict postnatal CoA. The scoring system permitted a better identification of the affected fetuses.

Background—It is recognized that inflammation is an underlying cause of dry eye disease (DED), with cytokine release involved. We systematically reviewed literature with meta-analyses to quantitatively summarize the levels of tear cytokines in DED. Methods—The PubMed, Embase, Web of Science, Ovid, Cochrane, and Scopus databases were reviewed until September 2019, and original articles investigating tear cytokines in DED patients were included. Differences of cytokines levels of DED patients and controls were summarized by standardized mean differences (SMD) using a random effects model. Study quality was assessed by applying Newcastle-Ottawa-Scale and the GRADE quality score. Methods of analytical procedures were included as covariate. Results—Thirteen articles investigating 342 DED patients and 205 healthy controls were included in the meta-analysis. The overall methodological quality of these studies was moderate. Systematic review of the selected articles revealed that DED patients had higher tear levels of interleukin (IL)-1β, IL-6, chemokine IL-8, IL-10, interferon-γ, IFN-γ, and tumor necrosis factor-α, TNF-α as compared to controls. Evidence was less strong for IL-2 and IL-17A. Conclusions—Data show that levels of tear cytokines in DED and control display a great variability, and further studies of higher quality enrolling a higher number of subjects are needed, to define a cut-off value.

Background: The role of thrombus aspiration plus primary percutaneous coronary intervention in ST-segment elevation myocardial infarction remains controversial. Methods: We performed a meta-analysis of 25 randomised controlled trials in which 21,740 ST-segment elevation myocardial infarction patients were randomly assigned to thrombus aspiration plus primary percutaneous coronary intervention or primary percutaneous coronary intervention. Study endpoints were: death, myocardial infarction, stent thrombosis and stroke. Results: On pooled analysis, the risk of death (4.3% vs. 4.8%, odds ratio (OR) 0.90, 95% confidence interval (CI) 0.79–1.03; P=0.123), myocardial infarction (2.4% vs. 2.5%, OR 0.95, 95% CI 0.80–1.13; P=0.57) and stent thrombosis (1.3% vs. 1.6%, OR 0.80, 95% CI 0.63–1.01; P=0.066) was similar between thrombus aspiration plus primary percutaneous coronary intervention and primary percutaneous coronary intervention. The risk of stroke was higher in the thrombus aspiration plus primary percutaneous coronary intervention than the primary percutaneous coronary intervention group (0.84% vs. 0.59%, OR 1.401, 95% CI 1.004–1.954; P=0.047). However, on sensitivity analysis after removing the TOTAL trial, thrombus aspiration plus primary percutaneous coronary intervention was not associated with an increased risk of stroke (OR 1.01, 95% CI 0.58–1.78). The weak association between thrombus aspiration and stroke was also confirmed by the fact that the lower bound of the 95% CI was slightly below unity after removing either the study by Kaltoft or the ITTI trial. There was no interaction between the main study results and follow-up, evidence of coronary thrombus, or study sample size. Conclusions: In patients with ST-segment elevation myocardial infarction, thrombus aspiration plus primary percutaneous coronary intervention does not reduce the risk of death, myocardial infarction or stent thrombosis. Thrombus aspiration plus primary percutaneous coronary intervention is associated with an increased risk of stroke; however, this latter finding appears weak.

Aims Cardiac amyloidosis remains a great challenge for the cardiologist. One of the three main aetiological forms, transthyretin-related hereditary amyloidosis (ATTRm), can present with several phenotypes, depending mainly on the specific mutation. We aimed to characterize the phenotype of patients with ATTRm due to Ile68Leu mutation, comparing them to patients with wild-type transthyretin amyloidosis (ATTRwt). Methods and results Data of 67 Ile68Leu ATTRm patients from two Italian referral centres (Bologna and Florence) were retrospectively analysed and compared to those of 82 ATTRwt patients. Fifty-five unaffected mutation carriers were also analysed. Cumulative disease onset was 50% at age 71. A total of 56/67 (84%) patients had a predominantly cardiac phenotype at presentation with concentric increase in left ventricular wall thickness [median 17 mm], and normal or near normal left ventricular ejection fraction (79% of patients). Low QRS voltages were present only in 29% of patients but voltage/mass ratio was low (0.5). Carpal tunnel syndrome was noted in 43%. The overall phenotypic profile was similar to ATTRwt but Ile68Leu ATTRm patients typically presented younger (median 71 vs. 78 years) and were more likely to have (mild) symptomatic neurological involvement (19% vs. 2%). Male prevalence was 44% in unaffected mutation carriers and 78% in affected patients. Age-adjusted survival was comparable between groups. Conclusions Ile68Leu ATTRm is a cause of familial amyloidotic cardiomyopathy endemic in central-northern Italy and presents as hypertrophic/restrictive cardiomyopathy quite similar to ATTRwt. Male preponderance is present in affected patients but not in unaffected mutation carriers. Age-adjusted survival is similar to ATTRwt.

Objective To investigate differences in cardiac manifestations of patients affected by laminopathy, according to the presence or absence of neuromuscular involvement at presentation. Methods We prospectively analyzed 40 consecutive patients with a diagnosis of laminopathy followed at a single centre between 1998 and 2017. Additionally, reports of clinical evaluations and tests prior to referral at our centre were retrospectively evaluated. Results Clinical onset was cardiac in 26 cases and neuromuscular in 14. Patients with neuromuscular presentation experienced first symptoms earlier in life (11 vs 39 years; p p = 0.013] and 30 vs 44 years [p = 0.086] respectively), despite a similar overall prevalence of AF (57% vs 65%; p = 0.735) and atrio-ventricular (A-V) block (50% vs 65%; p = 0.500). Those with a neuromuscular presentation developed a cardiomyopathy less frequently (43% vs 73%; p = 0.089) and had a lower rate of sustained ventricular tachyarrhythmias (7% vs 23%; p = 0.387). In patients with neuromuscular onset rhythm disturbances occurred usually before evidence of cardiomyopathy. Despite these differences, the need for heart transplantation and median age at intervention were similar in the two groups (29% vs 23% [p = 0.717] and 43 vs 46 years [p = 0.593] respectively). Conclusions In patients with laminopathy, the type of disease onset was a marker for a different natural history. Specifically, patients with neuromuscular presentation had an earlier cardiac involvement, characterized by a linear and progressive evolution from rhythm disorders (AF and/or A-V block) to cardiomyopathy.

Post-reperfusion syndrome during orthotopic liver transplantation, which definition best predicts postoperative graft failure and recipient mortality? Purpose Post-reperfusion syndrome (PRS) is a serious complication of liver transplantation, at present two main definitions are in use, and they differ both clinically and temporally. The primary objective of this study was to evaluate these two definitions as risk factors for post-transplantation mortality and primary graft non-function. Materials and methods We conducted a retrospective observational study on 794 patients undergoing orthotopic liver transplantation at our university hospital. The presence of PRS was evaluated according to both definitions and correlated with the end points: three months mortality, primary graft non-function (PGNF) and the combined outcome of the two. Results Both definitions proved to be independent risk factors for three months mortality and the combined outcome. The definition according to Aggarwal et al. was also an independent risk factor for PGNF when adjusted for the propensity score. The Hilmi definition, despite being more comprehensive, did not improve the predictivity of the Aggarwal definition for the evaluated outcomes. Conclusions PRS proved to be an independent risk factor for post-transplantation mortality and occurrence of PGNF. The pathophysiological mechanisms of this entity are still not fully understood and preventive strategies could help in reducing patients and graft losses.

Purpose To evaluate the outcome of patients with an established indication for oral anticoagulation (OAC) undergoing coronary stent implantation (PCI-S) and stratified by the baseline risk of bleeding. Material and methods The database of the prospective, multicentre, observational WAR-STENT registry ( ClinicalTrials.gov identifier NCT00722319 ) was analyzed and patients with atrial fibrillation and CHA 2 DS 2 -VASc score ≥2, mechanical heart valve, prior cardiac embolism, intra-cardiac thrombus and recent venous thromboembolism who were treated with either triple (warfarin, aspirin and clopidogrel) or dual (warfarin and clopidogrel) or dual antiplatelet (aspirin and clopidogrel) therapy, identified. Patients were then sorted into two groups at non-low and low risk of bleeding, as defined by an ATRIA score >3 and ≤3 respectively, and compared regarding major adverse cardiac and vascular events (MACVE) and bleeding. Results At 12-month follow up, MACVE were comparable in the two groups, whereas total, major and minor bleeding, as well as combined MACVE and total bleeding, were significantly more frequent in the non-low bleeding risk group. Upon Cox univariate and multivariable analysis, non-low bleeding risk category confirmed as an independent predictor of major bleeding. The choice of antithrombotic therapy however, appeared not to be influenced by the bleeding risk category at baseline. Conclusions In patients with an established indication for OAC undergoing PCI-S, non-low bleeding risk category is the most potent independent predictor of major bleeding. Stratification of the bleeding risk at baseline should therefore be regarded as an indispensable process to be carried out before selection of the antithrombotic therapy.

Aims Pulmonary hypertension (PH) is a relevant complication of left heart disease (LHD). The 2015 ESC/ERS PH guidelines report two different haemodynamic subsets of PH due to LHD (PH-LHD) based on levels of pulmonary vascular resistance (PVR) and diastolic pressure gradient (DPG): isolated post-capillary PH (Ipc-PH) and combined post- and pre-capillary PH (Cpc-PH). The objective of this study is to evaluate the prognostic value of Ipc-PH and Cpc-PH. Methods and results Data from 276 consecutive incident patients with PH-LHD were included. According to the guidelines, Ipc-PH is defined by DPG 3 WU. Using this definition, we identified three patient groups: Ipc-PH with both normal PVR and DPG (108 patients); Cpc-PH with both increased PVR and DPG (66 patients); and an intermediate group with either increased PVR or DPG (102 patients). Survival was estimated using the Kaplan–Meier method and compared between groups using the log-rank test. Patients with Ipc-PH had better survival compared with the group of patients with Cpc-PH (P = 0.026) and the intermediate group (P = 0.025). No survival difference was detected between patients with Cpc-PH and the intermediate group (P = 0.891). Patients with normal PVR had a better survival compared with those with elevated PVR (P = 0.012); while no difference was observed according to the level of DPG (P = 0.253). Conclusion Patients with Ipc-PH have a better prognosis compared with patients with Cpc-PH and with patients with isolated increase of PVR or DPG. Pulmonary vascular resistance has a better predictive value than DPG in patients with PH-LHD.

Our results confirm the diagnostic role of CTPA in evaluating patients with CTEPH and in addition open a new horizon in assessing hemodynamic changes in patients with CTEPH, only employing a CTPA, especially when RHC is contraindicated or not possible. Purpose: The aim of this study was to retrospectively assess the relationship between radiological and hemodynamic parameters in patients with chronic thromboembolic pulmonary hypertension (CTEPH). We introduced a new CT-score to evaluate hemodynamic changes, only employing CT-pulmonary angiography (CTPA). Materials and methods: 145 patients affected by CTEPH underwent hemodynamic and CTPA evaluation. Among these 145 patients, 69 underwent pulmonary endarterectomy (PEA) and performed a CTPA evaluation even after surgery. Hemodynamic assessment considered the values of mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR), obtained through right heart catheterization (RHC). Radiological evaluation included CTPA signs of pulmonary hypertension. Results: A highly significant statistical correlation was observed between the new CT-score and both mPAP and PVR (p < 0.000) in the whole sample and also in the subgroup who underwent PEA. In addition, mPAP and PVR showed an important association with the severity of mosaic perfusion (p < 0.000). mPAP also correlated with main pulmonary artery diameter (p < 0.01); a significant association was found in both between PVR and tricuspid regurgitation(p < 0.000) and with PVR and presence of unilateral or bilateral pulmonary thromboembolic occlusion (p < 0.05). Conclusion: Our results confirm the diagnostic role of CTPA in evaluating patients with CTEPH and in addition open a new horizon in assessing hemodynamic changes in patients with CTEPH, only employing a CTPA, especially when RHC is contraindicated or not possible.

Background Real-life data on the use of pirfenidone and nintedanib to treat patients with idiopathic pulmonary fibrosis (IPF) are still scarce. Methods We compared the efficacy of either pirfenidone (n = 78) or nintedanib (n = 28) delivered over a 24-month period in patients with IPF, followed at two regional clinic centers in Italy, with a group of patients who refused the treatment (n = 36), and who were considered to be controls. All patients completed regular visits at 1- to 3-month intervals, where primary [forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO)] and secondary outcomes (side effects, treatment compliance, and mortality) were recorded. Results Over time, the decline in FVC and DLCO was significantly higher (p = 0.0053 and p = 0.037, respectively) in controls when compared with the combined treated group, with no significant difference between the two treated groups. Compared to patients with less advanced disease (GAP (Gender, Age, Physiology) stage I), those in GAP stages II and III showed a significantly higher decline in both FVC and DLCO irrespective of the drug taken. Side effects were similarly reported in patients receiving pirfenidone and nintedanib (5% and 7%, respectively), whereas mortality did not differ among the three groups. Conclusion This real-life study demonstrated that both pirfenidone and nintedanib were equally effective in reducing the decline of FVC and DLCO versus non-treated patients after 24 months of treatment; however, patients with more advanced disease were likely to show a more rapid decline in respiratory function.

Background: Although imaging techniques have demonstrated the existence of microvascular abnormalities in hypertrophic cardiomyopathy (HCM), a detailed histopathological assessment is lacking as well as a comparison between different phases of the disease. We aimed to compare microvasculopathy and myocardial fibrosis in hypertrophic obstructive cardiomyopathy (HOCM) versus end-stage (ES) HCM. Methods: 27 myectomy specimens of HOCM patients and 30 ES-HCM explanted hearts were analyzed. Myocardial fibrosis was quantitatively determined with dedicated software and qualitatively classified as scar-like or interstitial. Intramural coronary arteries were evaluated separately according to lumen diameter: 100–500 μ versus

Left bundle branch block (LBBB) is the most reliable electrocardiographic predictor of responsiveness to cardiac resynchronization therapy (CRT). However, not all patients with LBBB will respond to CRT. Our aim was to investigate the interaction between QRS duration, LBBB-type morphology, and the responsiveness to CRT. We retrospectively analyzed electrocardiograms of 243 patients who underwent CRT implantation according to current clinical indications. A 6-month reduction of left ventricular end-systolic volume >15% was used to identify CRT responders. The clinical end point consisted of death, hospitalization for heart failure and sustained rapid ventricular tachyarrhythmias. An LBBB morphology was present in 169 patients (70%) and 101 of these (60%) were responders to CRT. Analyzing the interaction between QRS duration and CRT responsiveness in patients with LBBB, a "U shaped" distribution resulted, with nonresponders clustered between 120 and 130 ms and above 180 ms. The receiver operating characteristic curve analysis identified 178 ms as the optimal cut-off value of QRS to predict a nonresponsiveness to CRT (area under the curve = 0.67 [95% confidence interval 0.57 to 0.76]). At multivariate analysis, only an ischemic cause and a QRS ≥178 ms were independent predictors of nonresponsiveness to CRT (area under the curve = 0.75). Patients with LBBB with QRS ≥178 ms had greater likelihood of adverse clinical events during a mean follow-up of 32 months (p = 0.049). In conclusion, in patients with LBBB undergoing CRT, a marked QRS widening (i.e., ≥178 ms) is related to worse echocardiographic responsiveness and lower event free survival rate compared with patients with an intermediate QRS widening. Left bundle branch block (LBBB) is the most reliable electrocardiographic predictor of responsiveness to cardiac resynchronization therapy (CRT). However, not all patients with LBBB will respond to CRT. Our aim was to investigate the interaction between QRS duration, LBBB-type morphology, and the responsiveness to CRT. We retrospectively analyzed electrocardiograms of 243 patients who underwent CRT implantation according to current clinical indications. A 6-month reduction of left ventricular end-systolic volume >15% was used to identify CRT responders. The clinical end point consisted of death, hospitalization for heart failure and sustained rapid ventricular tachyarrhythmias. An LBBB morphology was present in 169 patients (70%) and 101 of these (60%) were responders to CRT. Analyzing the interaction between QRS duration and CRT responsiveness in patients with LBBB, a "U shaped" distribution resulted, with nonresponders clustered between 120 and 130 ms and above 180 ms. The receiver operating characteristic curve analysis identified 178 ms as the optimal cut-off value of QRS to predict a nonresponsiveness to CRT (area under the curve = 0.67 [95% confidence interval 0.57 to 0.76]). At multivariate analysis, only an ischemic cause and a QRS ≥178 ms were independent predictors of nonresponsiveness to CRT (area under the curve = 0.75). Patients with LBBB with QRS ≥178 ms had greater likelihood of adverse clinical events during a mean follow-up of 32 months (p = 0.049). In conclusion, in patients with LBBB undergoing CRT, a marked QRS widening (i.e., ≥178 ms) is related to worse echocardiographic responsiveness and lower event free survival rate compared with patients with an intermediate QRS widening.

AIMS: Despite troponin assay being a part of the diagnostic work up in many conditions with acute chest pain, little is known about its frequency and clinical implications in acute aortic syndromes (AASs). In our study we assessed frequency, impact on diagnostic delay, inappropriate treatments, and prognosis of troponin elevation in AAS.METHODS AND RESULTS: Data were collected from a prospective metropolitan AAS registry (398 patients diagnosed between 2000 and 2013). Cardiac troponin test, using either standard or high sensitivity assay, was performed according to standard protocol used in chest pain units. Troponin T values were available in 248 patients (60%) of the registry population; the overall frequency of troponin positivity was 28% (ranging from 16% to 54%, using standard or high sensitivity assay respectively, p = 0.001). Troponin positivity was frequently associated with acute coronary syndromes (ACS)-like electrocardiogram findings, and with a twofold increased risk of long in-hospital diagnostic time (odds ratio (OR) 1.92, 95% confidence interval (CI) 1.05-3.52, p = 0.03). The combination of positive troponin and ACS-like electrocardiogram abnormalities resulted in a significantly increased risk of in-hospital delay/coronary angiography/antithrombotic therapy due to a misdiagnosis of ACS (OR 2.48, 95% CI 1.12-5.54, p = 0.02). However, troponin positivity was not associated with in-hospital mortality (OR 1.63, 95% CI 0.86-3.10, p = 0.131).CONCLUSIONS: Troponin positivity was a frequent finding in AAS patients, particularly when a high sensitivity assay was employed. Abnormal troponin values were strongly associated with ACS-like electrocardiogram findings and with in-hospital diagnostic delay but apparently they did not influence in-hospital mortality.

Background & aims The treatment of chronic hepatitis B infection (CHB) in children is still an area of great uncertainty. Vitamin E is an immunostimulating/antioxidant compound proven to be safe and effective for the treatment of adult CHB. The aim of this phase 2 controlled study was to evaluate the safety and efficacy of vitamin E for the treatment of paediatric HBeAg-positive CHB. Methods Forty-six children were randomized in a 1:1 ratio to receive vitamin E at a dose of 15 mg/kg/day (in galenic preparation) or no treatment for 12 months and were monitored for the subsequent 12 months. Clinical, biochemical, haematological and serovirological evaluations were carried out every 3 months. Results No significant side effects were associated with the vitamin E treatment. At the end of the study, anti-HBe seroconversion was obtained in 7 of 23 (30.4%) of vitamin E-treated versus 1 of 23 (4.3%) of the control patients (P = 0.05), while a virological response (≥2 log decrease in HBV-DNA from baseline) was observed in 9 of 23 (39.1%) vs. 2 of 23 (8.7%) respectively (P = 0.035). Conclusions Vitamin E administration for the treatment of paediatric CHB at the tested dosage has no significant side effects and may induce anti-HBe seroconversion. Vitamin E could represent a tool for the treatment of paediatric CHB.

We sought to investigate the prognostic significance of prodromal angina (PA) in unselected patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI) and its additive predictive value to the GRACE score. We prospectively enrolled 3015 consecutive STEMI patients undergoing PPCI. Patients were divided in 2 groups according to the presence or absence of PA. Multivariable Cox regression was used to establish the relation to 2-year cardiac mortality of PA. The mean age of the study population was 68 (±14) years; 2178 patients (72%) were male. During follow-up, 395 (13%) patients died with 278 of these (9.2%) suffering from cardiac mortality. Kaplan-Meier estimates showed a survival rate of 95% and 87% for patients with PA and no PA, respectively (log rank test

Objective Malignant aortic tumors (MATs) are exceedingly rare, and a comprehensive review of clinical and therapeutic aspects is lacking in the literature. The aim of this study was to analyze all known cases of MATs and to identify predictors of patients' survival. Methods All patients diagnosed with an aortic tumor treated in a single center along with all case reports and reviews available in the literature through a specific PubMed search using keywords such as “malignant” and “aorta” or “aortic,” “tumor,” or “sarcoma” or “angiosarcoma” were analyzed. The tumor's primary location, clinical presentation, histologic subtype, and treatment choice were examined. Survival at 1 year, 3 years, and 5 years and the possible preoperative and operative outcome predictors were evaluated using Kaplan-Meier analysis with a log-rank test and by Cox regression for multivariate analysis. Results In addition to the 5 cases treated in our center, 218 other cases of MAT were reported in the literature from 1873 to 2017. The mean age of the patients was 60.1 ± 11.9 years, and the male to female ratio was 1.59:1. The median overall survival from diagnosis was 8 (7-9) months; 1-, 3-, and 5-year survival rates were 26%, 7.6%, and 3.5%, respectively. Chronic hypertension (P = .03), fever (P = .03), back pain (P = .01), asthenia (P = .04), and signs of peripheral embolization (P = .007) were significant predictors of a poor result. Histologic subtypes had a different impact on survival, with no statistical significance. Compared with other treatment strategies, combined surgical-medical therapy had the best impact on the median survival rate (surgical-medical, 12 [8-24] months; medical, 8 [5-10] months; surgical 7 [2-16] months; no treatment, 2 [0.5-15] months; P = .001). Analyzing exclusively medical approaches, chemotherapy and radiotherapy had the best impact on median survival rate compared with untreated patients (chemotherapy-radiotherapy, 18 [10-26] months; radiotherapy, 16 [8-20] months; chemotherapy, 10 [7-24] months; no medical treatment, 6 [2-16] months; P = .005); these data were not sustained by multivariate analysis. Conclusions Aortic tumors are a malignant pathologic condition with a short survival rate after initial diagnosis. Survival is further diminished in the presence of clinical factors such as hypertension, fever, back pain, asthenia, and signs of peripheral embolization. Combined surgical and medical treatment, particularly with chemotherapy and radiotherapy, has shown the highest survival rate.

Background Infectious complications represent one of the main causes of perioperative morbidity and mortality of liver transplant recipients. The primary objective of this retrospective observational study was to evaluate incidence and etiology of early (within 1 month from surgery and occurring in the intensive care unit [ICU]) postoperative infections as well as donor- and recipient-related risk factors. Methods The data of 280 patients undergoing 299 consecutive liver transplant procedures from January 2012 to December 2015 were extracted from the Italian ICU registry database and hospital registries. Perioperative risk factors, etiology of infections, and antibiotic susceptibility of isolated microorganisms were taken into consideration. Results Global incidence of postoperative infections was 21%. Pneumonia was the most frequent infection and, globally, gram-negative bacteria were the most common agents. Septic shock was present in 22% of infection cases and hospital mortality was higher in patients with postoperative infection. Preoperative chronic obstructive pulmonary disease, malnutrition, preoperative ascites, encephalopathy, and early re-transplantation were significantly associated to post orthotopic LT infections. Conclusion Infections represent a major cause of early postoperative morbidity and mortality. The impact of single risk factors and the results of their preoperative management should be further investigated in order to reduce the incidence and evolution of postoperative infections.

Objective To determine, in patients with ST-segment Elevation Myocardial Infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI), the prognostic weight of cardiac arrest (CA) according to the type of rhythm (shockable vs. non-shockable). Methods We prospectively enrolled 3278 consecutive STEMI patients undergoing PPCI. Multivariable Cox regression was used to establish the relation to 1-year cardiac mortality of both type of CA. In patients suffering from CA we identified predictors of both poor neurological outcome (cerebral performance categories 3–5) and cardiac mortality at 1 year. Results The incidence of CA was 7.26% (n = 238). Of these, 196 (5.98%) had an initial shockable rhythm and 42 (1.28%) a non shockable rhythm. During 1-year follow up 311(9.48%) patients died from cardiac causes. Shockable rhythm (adjusted-HR = 1.61; 95%CI 1.08–2.43, p = 0.02) and non-shockable rhythm (adjusted-HR = 3.83; 95%CI 2.36–6.22, p < 0.001) were independently associated with 1-year cardiac mortality. Among patients with CA those with shockable rhythm had a lower risk of poor neurological outcome at 1 year follow up (adjusted OR = 0.22: 95%CI; 0.08–0.55, p = 0.001). Independent predictors of 1-y cardiac mortality were: non shockable rhythm (adjusted HR = 2.6; 95%CI; 1.48–4.5, p = 0.001), crew-witnessed CA, diabetes mellitus, left ventricle ejection fraction and creatinine on admission. There was a significant interaction between type of rhythm and crew-witnessed CA (p = 0.026). Conclusions In patients with STEMI undergoing PPCI patients with both shockable and non shockable CA are at increased risk of 1-year cardiac mortality. Among patients with CA those with non shockable rhythm have an higher risk of both poor neurological outcome and cardiac mortality at 1 year.

Background: Direct-acting antivirals (DAA) are an effective treatment for hepatitis C virus infection. However, sustained virologic response (SVR) after DAA treatment does not seem to reduce the risk of hepatocellular carcinoma (HCC) development in these patients. Liver stiffness measurement (LSM) may predict the risk of developing HCC in liver cirrhosis patients. Aims: The aim of our study was to evaluate the role of LSM variation as predictor of HCC development in patients treated with DAA. Methods: In 139 HCV-related cirrhotic patients, LSM and laboratory tests were carried out at baseline (BL) and at the end of DAA treatment (EOT). Patients were followed for at least 6 months after the EOT. LSM reduction was expressed as Delta LS (∆LS). Cox regression analysis was used to identify prognostic factors for HCC development after DAA. Results: Median LSM values were significantly reduced from BL to EOT (from 18.6 to 13.8 kPa; p < 0.001). The median ∆LS was −26.7% (IQR: −38.4% −13.6%). During a median follow-up of 15 months after DAA treatment, 20 (14.4%) patients developed HCC. Significant LSM reduction was observed both in patients who developed HCC and in those who did not, but this was significantly lower in the patients who developed HCC (−18.0% vs −28.9% p = 0.005). At multivariate analysis, ∆LS lower than −30%, Child-Turcotte-Pugh-B and history of HCC were independently associated with HCC development. Conclusion: Our results indicate that ∆LS is a useful non-invasive marker for predicting HCC development after DAA treatment.

Background: Chronic kidney disease (CKD) is associated with adverse outcomes in presence of atrial fibrillation (AF). However, the literature shows limited data on non-pharmacological management of AF in CKD patients. Aim: summarizing the available data on outcomes associated with electrical cardioversion (ECV) and AF catheter ablation (CA) in CKD patients. Methods: We searched MEDLINE and the Cochrane Central Register of Controlled Trials and performed a metaanalysis. The primary outcome was recurrence of AF. The secondary outcomes were occurrence of thromboembolic events (TEs) and estimated glomerular filtration rate (eGFR) modification. Results: Literature search yielded 26 eligible papers: 22 on CA and 4 concerning ECV. CKD patients presented more AF recurrences 30 days after ECV (OR 2.62, 95%CI 1.28-5.34; p Conclusion: ECV and CA for sinus rhythm restoration/maintenance in AF patients, albeit theoretically promising, seem to be associated with lower efficacy at medium to long-term in patients with CKD. Further studies are needed to better define the role of ECV and CA in CKD.

Recently, the myelofibrosis secondary to PV and ET prognostic model (MYSEC-PM) was introduced to assess prognosis in myelofibrosis (MF) secondary to polycythemia vera and essential thrombocythemia (post-PV and post-ET MF), replacing the International Prognostic Scoring System (IPSS) and/or Dynamic IPSS (DIPSS) that was applied for primary MF (PMF). In a cohort of 421 ruxolitinib (RUX)-treated patients (post-PV and post-ET MF: 44.2%), we evaluated the following: (1) disease phenotype, responses, and toxicity to RUX; and (2) performance of the MYSEC-PM in post-PV or post-ET ME. While the IPSS failed to correctly stratify post-PV or post-ET MF patients at diagnosis, the MYSEC-PM identified 4 risk categories projected at significantly different survival probability (P < .001). Additionally, the MYSEC-PM maintained a prognostic value in post-PV and post-ET MF also when used over time, at RUX start. Notably, the MYSEC-PM reclassified 41.8% and 13.6% of patients into a lower and higher risk category, respectively. Finally, patients at intermediate-1 risk had significantly higher spleen responses and lower hematological toxicities compared to higher risk patients. Compared to PMF, post-PV and post-ET MF presented a more hyperproliferative disease, with higher leukocyte and/or platelet count and hemoglobin levels both at diagnosis and at RUX start. Despite comparable response rates, post-PV and post-ET MF had lower rate of RUX-induced anemia and thrombocytopenia at 3 and 6 months. The study validates MYSEC-PM in post-PV and post-ET MF prognostication. Post-PV or post-ET MF represents a separate entity compared to PMF in terms of clinical manifestations and toxicity to RUX. (C) 2018 Elsevier Inc. All rights reserved.

none 12 no Programma di ricerca Regione-Università, RegioneEmilia-Romagna2010-2012 — Area1Innovativeresearch.Title: Technological innovations in the treatment of heart failure ” Objectives: To compare the effectiveness and safety of balloon aortic valvuloplasty (BAV) performed with or without rapid ventricular pacing (RP). Background: BAV technique is poorly standardized. Methods: One hundred consecutive patients were randomly assigned 1:1 between BAV performed with or without RP. Exclusion criteria were an immediate indication for surgical or transcatheter aortic valve replacement, presentation in cardiogenic shock or pulmonary edema refractory to medical stabilization. Results: There were 51 patients in the BAV group performed with RP, 49 in the BAV group without RP (noRP). Procedural success (50% hemodynamic gradient reduction) was achieved in 37.3% and 55.1%, respectively (P=0.16). Fewer people in the noRP group complained of poor tolerance to the procedure (16% vs 41%). The primary efficacy endpoint, a 50% reduction in the mean echocardiographic trans-aortic gradient, was met in 21/49 patients in the noRP group compared to 20/51 in the RP (42.9% vs 39.2%; P=0.84). No significant difference between the groups was observed in the primary safety endpoint, a 30-day composite of death, myocardial infarction, stroke, acute aortic regurgitation, and BARC bleeding ≥3 (8.2% noRP vs 13.7%; P=0.53). The noRP group required fewer bailout temporary pacemakers (P=0.048) and had a lower incidence of moderate/severe renal function worsening (4.1% vs 17.6%; P=0.052). Conclusions: Rapid ventricular pacing did not influence BAV efficacy or safety and tolerance was slightly worse. none Dall'Ara, Gianni; Marzocchi, Antonio; Taglieri, Nevio; Moretti, Carolina; Rodinò², Giulio; Chiarabelli, Matteo; Bottoni, Paolo; Marrozzini, Cinzia; Sabattini, Maria Rita; Bacchi-Reggiani, Maria-Letizia; Rapezzi, Claudio; Saia, Francesco Dall'Ara, Gianni; Marzocchi, Antonio; Taglieri, Nevio; Moretti, Carolina; Rodinò², Giulio; Chiarabelli, Matteo; Bottoni, Paolo; Marrozzini, Cinzia; Sabattini, Maria Rita; Bacchi-Reggiani, Maria-Letizia; Rapezzi, Claudio; Saia, Francesco

Background Atrial fibrillation (AF) is associated with high morbidity and mortality, also among anticoagulated patients. Our aim was to evaluate the predictive role for long-term mortality of a series of risk stratification scores associated with cardiovascular or thromboembolic outcomes (CHADS 2 , CHA 2 DS 2 -VASc, ATRIA, TIMI-AF), and bleeding complications (HAS-BLED) in an unselected population of patients with AF. Methods Single center, observational, prospective registry of consecutive patients with AF, undergoing clinical/echocardiographic evaluation in a University Hospital, as either in-patients or out-patients. We assessed the role of each single score as predictors of long-term survival according to clinical setting. Results We enrolled 1051 patients, mean age 72 ± 12 years, who were followed for 797 ± 298 days. All the tested scores showed a good performance in prediction of mortality, together with several clinical factors (older age, chronic heart failure, diabetes, renal impairment, previous transient ischemic attack, left ventricular ejection fraction). The values at C-statistics ranged between modest (0.608–0.684) of inpatients to good (0.708–0.751) in outpatients without any statistical difference between the scores, excepted a lower performance of HAD-BLED. Conclusions Risk scores currently adopted for decision making on starting oral anticoagulation provide good prediction of long-term survival in unselected AF patients, especially in the outpatient setting.

Background Pancreatic adenocarcinoma (PDAC) is one of the deadliest human malignancies. Although surgery is currently the only effective treatment for PDAC, most patients survive less than 20 months after tumor resection. Objective The primary goal was to investigate alterations in KRAS, TP53, SMAD4 and CDKN2A/p16 in tumors from patients with exceptionally long survival after surgery. Methods Tumors from 15 patients with PDAC that survived more than 55 months after surgery ("LS") were analyzed for KRAS, TP53, IDH1, NRAS and BRAF using next-generation sequencing. SMAD4 and CDKN2A/p16 was tested using immunohistochemistry. MGMT promoter methylation was investigated. Results Tumors from "LS" have a lower prevalence of KRAS and TP53 mutations and had more frequently SMAD4 retained expression, if compared with that of patients died within 24 months from surgery. The survival of patients with wild-type KRAS and TP53 tumors was more than twice longer than that of patients bearing KRAS and TP53 mutations (90.2 vs. 41.1 months). Patients with KRAS wild-type tumors and that retained SMAD4 expression had a survival twice longer than cases with alterations in both genes (83.8 vs. 36.7 months). Eleven tumors (39.3%) showed MGMT methylation. Conclusions Our data indicate that absence of KRAS, TP53 and SMAD4 genetic alterations may identify a subset of pancreatic carcinomas with better outcome.

Pulmonary arterial hypertension is a severe disease with a complex pathogenesis, for which combination therapy is an attractive option.This study aimed to assess the impact of sequential combination therapy on both short-term responses and long-term outcomes in a real-world setting.Patients with idiopathic/heritable pulmonary arterial hypertension, or pulmonary arterial hypertension associated with congenital heart disease or connective tissue disease and who were not meeting treatment goals on either first-line bosentan or sildenafil monotherapy, were given additional sildenafil or bosentan and assessed after 3–4 months. Double combination therapy significantly improved clinical and haemodynamic parameters, independent of aetiology or the order of drug administration. Significant improvements in functional class were observed in patients with idiopathic/heritable pulmonary arterial hypertension. The 1-, 3- and 5-year overall survival estimates were 91%, 69% and 59%, respectively. Patients with pulmonary arterial hypertension associated with connective tissue disease had significantly poorer survival rates compared to other aetiologies (pThe favourable short-term haemodynamic results and good survival rates, observed in patients receiving both bosentan and sildenafil, supports the use of sequential combination therapy in patients failing on monotherapy in a real-world setting.

Background: Drug withdrawal still remains the key element in the treatment of Medication Overuse Headache (MOH), but there is no consensus about the withdrawal procedure. Still debated is the role of the steroid therapy. The aim of this study was to evaluate the effectiveness of methylprednisolone or paracetamol in the treatment of withdrawal headache in MOH. Methods: We performed a pilot, randomized, single-blinded, placebo controlled trial. MOH patients, unresponsive to a 3 months prophylaxis, underwent withdrawal therapy on an inpatient basis. Overused medications were abruptly stopped and methylprednisolone 500mg i.v (A) or paracetamol 4g i.v. (B) or placebo i.v. (C) were given daily for 5days. Patients were monitored at 1 and 3months. Results: Eighty three consecutive MOH patients were enrolled. Fifty seven patients completed the study protocol. Nineteen patients were randomized to each group. Withdrawal headache on the 5th day was absent in 21.0% of group A, in 31.6% of group B and in 12.5% of group C without significant differences. Withdrawal headache intensity decreased significantly after withdrawal without differences among the groups. Rregardless of withdrawal treatment, 52% MOH patients reverted to an episodic migraine and 62% had no more medication overuse after 3 months. Conclusions: This study suggests that in a population of severe MOH patients, withdrawal headache decreased significantly in the first 5 days of withdrawal regardless of the treatment used. Methylprednisolone and paracetamol are not superior to placebo at the end of the detoxification program.

Purpose: To evaluate the relationship between aortic inflammation as assessed by18F–fluorodeoxyglucose-positron emission tomography (18F–FDG-PET) and features of plaque vulnerability as assessed by frequency domain-optical coherence tomography (FD-OCT). Methods: We enrolled 30 consecutive non-ST-segment elevation acute coronary syndrome patients undergoing percutaneous coronary intervention. All patients underwent three-vessel OCT before intervention and18F–FDG-PET before discharge. Univariable and C-reactive protein (CRP)-adjusted linear regression analyses were performed between features of vulnerability [namely:lipid-rich plaques with and without macrophages and thin cap fibroatheromas (TCFA)] and18F–FDG uptake in both ascending (AA) and descending aorta (DA) [measured either as averaged mean and maximum target-to-blood ratio (TBR) or as active slices (TBRmax ≥ 1.6)]. Results: Mean age was 62 years, and 26 patients were male. On univariable linear regression analysis TBRmeanand TBRmaxin DA was associated with the number of lipid-rich plaques (β = 4.22; 95%CI 0.05–8.39; p = 0.047 and β = 3.72; 95%CI 1.14–6.30; p = 0.006, respectively). TBRmaxin DA was also associated with the number of lipid-rich plaques containing macrophages (β = 2.40; 95%CI 0.07–4.72; p = 0.044). A significant CRP adjusted linear association between the TBRmaxin DA and the number of lipid-rich plaques was observed (CRP-adjusted β = 3.58; 95%CI -0.91-6.25; p = 0.01). TBRmaxin DA showed a trend towards significant CRP-adjusted association with number of lipid-rich plaques with macrophages (CRP-adjusted β = 2.30; 95%CI -0.11-4.71; p = 0.06). We also observed a CRP-adjusted (β = 2.34; 95%CI 0.22–4.47; p = 0.031) linear association between the number of active slices in DA and the number of lipid-rich plaques. No relation was found between FDG uptake in the aorta and the number of TCFAs. Conclusions: In patients with first NSTEACS, 18F–FDG uptake in DA is correlated with the number of OCT detected lipid-rich plaques with or without macrophages. This association may be independent from CRP values.

Background Left main coronary artery (LMCA) compression is increasingly recognized as a cause of angina in pulmonary arterial hypertension (PAH). Objectives This study aimed to evaluate the prevalence of LMCA extrinsic compression from a dilated pulmonary artery (PA) in patients with PAH and angina or angina-like symptoms, determine the usefulness of screening with computed tomography coronary angiography (CTCA), and assess the safety and efficacy of percutaneous coronary interventions (PCIs). Methods All patients with PAH and angina or angina-like symptoms attending the center between May 1, 2008, and December 31, 2013, underwent CTCA. Patients with confirmed LMCA stenosis on selective coronary angiography had PCI. Results Of 765 patients with PAH, 121 had angina or angina-like symptoms. Ninety-four patients had abnormal CTCA based on the relationship between the PA and the LMCA and underwent selective coronary angiography. LMCA stenosis ≥50% was detected in 48 of the 94 patients. Forty-five patients underwent PCI with stenting, of whom 41 had sustained angina symptom relief. The 3 other patients had surgical PA reduction plasty. Nine months after PCI, 5 patients had LMCA restenosis and PCI was successfully repeated. The best predictor of LMCA stenosis ≥50% was a PA diameter ≥40 mm. Rates for death or double-lung transplant and the composite rates for death, double-lung transplant, or restenosis at 36 months were 5% and 30%, respectively. Conclusions The prevalence of LMCA compression in patients with PAH and angina is high. These results suggest that CTCA is indicated in patients with PAH and angina or angina-like symptoms. PCI was well tolerated, improved symptoms, and resulted in favorable long-term outcomes.

Dronedarone was found to have divergent safety profiles in randomized controlled trials (RCT) in term of cardiac death and overall mortality. We decided to evaluate all available evidence on the cardiovascular safety of this drug. A systematic search was made of the MEDLINE and the Cochrane Central Register of Controlled Trials from January 2003 through April 2016 for RCT comparing dronedarone to placebo/active control, to provide the most accurate estimate of the effects of this agent and observational cohort studies (OBS) reporting clinical outcomes in patients treated with dronedarone, according to current guidelines, to obtain a real-life comparator for the findings summarized by RTC analysis. The literature search yielded 2335 papers and after careful review we identified 12 RCT and 7 OBS studies. RCT meta-analysis showed that, despite high heterogeneity, dronedarone was not associated with increased all-cause mortality [OR (Odds Ratio) 1.36, 95%CI (Confidence Interval) 0.79-2.33; p=0.732, I2=57.0%] or cardiovascular mortality [OR 1.51 95%CI 0.74-3.08; p=0.860, I2=64.4%]. OBS studies had a trend toward a better survival with respect to RCT [ES (Effect Size) 2.03, 95%CI 0.53-3.53 vs. ES 3.03, 95%CI 1.23-4.83; p=0.115], reaching the significance when restricted to the cardiovascular mortality [ES 0.52, 95%CI 0.36-0.69 vs. ES 1.86, 95%CI 0.62-3.09; p

The use of interferon gamma (IFN-γ) release assays (IGRAs) for the diagnosis of tuberculosis (TB) infection in children is still under debate because of concerns about the immature immune response in children. The aim of this study was to investigate quantitative values of the QuantiFERON-TB Gold In-Tube (QFT-IT) test, a commercially available IGRA, in a large cohort of children screened for TB infection. A retrospective analysis was conducted on samples from 517 children aged 0 to 14 years old at the Pediatric Unit of S. Orsola-Malpighi University Hospital of Bologna (Italy); quantitative responses to QFT-IT stimuli were analyzed according to diagnosis and age. Elevated IFN-γ values in the QFT-IT nil (background) tube were statistically associated with diagnosis of active TB. Quantitative IFN-γ response to Mycobacterium tuberculosis -specific antigens (TB Ag) was not significantly different in children with active TB compared to those with latent TB infection (LTBI), even though the median values were higher in the first group. When children were grouped by age, those less than 5 years old produced significantly higher levels of IFN-γ in response to TB Ag if they had active TB (median 10 IU/ml) than those with LTBI (median 1.96 IU/ml). IFN-γ response to mitogen increased with age. The overall rate of indeterminate results was low (3.9%), and no indeterminate QFT-IT values were observed in active or latent TB patients. In conclusion, quantitative QFT-IT values could provide further information to clinicians to manage TB in children, and these observations could be transferred to the new version of the test, QuantiFERON-TB Gold Plus, which to date lacks data from the pediatric population.

// Francesca Palandri 1 , Giuseppe Alberto Palumbo 2 , Massimiliano Bonifacio 3 , Mario Tiribelli 4 , Giulia Benevolo 5 , Bruno Martino 6 , Elisabetta Abruzzese 7 , Mariella D’Adda 8 , Nicola Polverelli 9 , Micaela Bergamaschi 10 , Alessia Tieghi 11 , Francesco Cavazzini 12 , Adalberto Ibatici 13 , Monica Crugnola 14 , Costanza Bosi 15 , Roberto Latagliata 16 , Ambra Di Veroli 17 , Luigi Scaffidi 3 , Federico de Marchi 4 , Elisa Cerqui 8 , Barbara Anaclerico 18 , Giovanna De Matteis 19 , Marco Spinsanti 1 , Elena Sabattini 1 , Lucia Catani 1 , Franco Aversa 14 , Francesco Di Raimondo 2 , Umberto Vitolo 5 , Roberto Massimo Lemoli 10 , Renato Fanin 4 , Francesco Merli 11 , Domenico Russo 9 , Antonio Cuneo 12 , Maria Letizia Bacchi Reggiani 20 , Michele Cavo 1 , Nicola Vianelli 1 and Massimo Breccia 16 1 Institute of Hematology “L. and A. Seragnoli”, Sant'Orsola-Malpighi University Hospital, Bologna, Italy 2 Division of Hematology, AOU 'Policlinico-V.Emanuele', Catania, Italy 3 Department of Hematology, University of Verona, Verona, Italy 4 Division of Hematology and BMT, Azienda Sanitaria Universitaria Integrata di Udine, Udine, Italy 5 Division of Hematology, Citta della Salute e della Scienza Hospital, Torino, Italy 6 Division of Hematology, Azienda Ospedaliera 'Bianchi Melacrino Morelli', Reggio Calabria, Italy 7 Division of Hematology, Ospedale S. Eugenio, Roma, Italy 8 Division of Hematology, ASST Spedali Civili di Brescia, Brescia, Italy 9 Unit of Blood Diseases and Stem Cell Transplantation, ASST Spedali Civili di Brescia, Brescia, Italy 10 Division of Hematology, IRCCS AOU San Martino-IST, Genova, Italy 11 Department of Hematology, A.O. Arcispedale Santa Maria Nuova – IRCCS, Reggio Emilia, Italy 12 Division of Hematology, University of Ferrara, Ferrara, Italy 13 Division of Hematology and Bone Marrow Transplant, IRCCS San Martino-IST, Genova, Italy 14 Division of Hematology, AOU of Parma, Parma, Italy 15 Department of Hematology and Bone Marrow Transplantation, A.O. of Piacenza, Italy 16 Division of Cellular Biotechnologies and Hematology, University Sapienza, Roma, Italy 17 Division of Hematology, Policlinico Tor Vergata, Roma, Italy 18 Division of Hematology, Ospedale S. Giovanni, Roma, Italy 19 Department of Life and Reproduction Sciences, Section of Clinical Biochemistry, University of Verona, Verona, Italy 20 Division of Cardiology, University of Bologna, Bologna, Italy Correspondence to: Francesca Palandri, email: francesca.palandri@unibo.it Keywords: myelofibrosis, splenomegaly, response, ruxolitinib, predictive factors Received: March 29, 2017 Accepted: May 15, 2017 Published: June 27, 2017 ABSTRACT In patients with Myelofibrosis (MF) treated with ruxolitinib (RUX), the response is unpredictable at therapy start. We retrospectively evaluated the impact of clinical/laboratory factors on responses in 408 patients treated with RUX according to prescribing obligations in 18 Italian Hematology Centers. At 6 months, 114 out of 327 (34.9%) evaluable patients achieved a spleen response. By multivariable Cox proportional hazard regression model, pre-treatment factors negatively correlating with spleen response were: high/intermediate-2 IPSS risk ( p =0.024), large splenomegaly ( p =0.017), transfusion dependency ( p =0.022), platelet count 2 years ( p =0.048). Also, patients treated with higher (≥10 mg BID) average RUX doses in the first 12 weeks achieved higher response rates ( p =0.019). After adjustment for IPSS risk, patients in spleen response at 6 months showed only a trend for better survival compared to non-responders. At 6 months, symptoms response was achieved by 85.5% of 344 evaluable patients; only a higher (>20) Total Symptom Score significantly correlated with lower probability of response ( p

Background The role of percutaneous mitral valve repair (PMVR) in patients with end-stage heart failure (HF) and functional mitral regurgitation (FMR) is unclear. Methods Seventy-five consecutive patients with FMR grade ≥ 3 + and severe HF symptoms despite optimal medical therapy and resynchronization therapy underwent PMVR with the MitraClip system (Abbott, Abbott Park, IL, USA) at 3 centers. Clinical evaluation, echocardiography and pro-BNP measurement were performed at baseline and at 6-month. Results Mean age was 67 ± 11 years, logistic EuroSCORE = 23 ± 18%, left ventricle ejection fraction (LVEF) 30 ± 9%. In 6 patients (8%) PMVR was performed as a bridge to heart transplant; many patients were dependent from iv diuretics and/or inotropes. Rate of serious adverse in-hospital events was 1.3% (1 patient who died after conversion to cardiac surgery). Sixty-three patients (84%) were discharged with MR ≤ 2 +. At 6-month, 4 patients died (5%), 80% had MR ≤ 2 + and 75% were in New York Heart Association class ≤ II. Median pro-BNP decreased from 4395 pg/ml to 2594 pg/ml (p = 0.04). There were no significant changes in LV end-diastolic volume (222 ± 75 ml vs. 217 ± 79, p = 0.19), end-systolic volume (LVESV, 154 ± 66 ml vs. 156 ± 69, p = 0.54) and LVEF (30 ± 9% vs. 30 ± 12%, p = 0.86). Significant reverse remodeling (reduction of LVESV ≥ 10%) was observed in 25%, without apparent association with baseline characteristics. The number of hospitalizations for HF in comparison with the 6 months before PMVR were reduced from 1.1 ± 0.8 to 0.3 ± 0.6 (p

Left ventricular (LV) dyssynchrony (LVdys) is a necessary condition for successful cardiac resynchronization therapy (CRT). Despite left bundle branch block (LBBB) representing a reliable surrogate of LVdys, not all LBBB patients will respond to CRT. Our aim was to investigate the relation between QRS duration and LVdys in patients with LBBB who underwent CRT. We retrospectively studied 165 patients with LBBB who underwent CRT implantation according to the current guidelines. A 6-month reduction of LV end-systolic volume ≥15% identified responders to CRT. Baseline LVdys was defined as the delay between peak systolic velocities of the interventricular septum and lateral wall assessed by color-coded tissue Doppler imaging. Baseline characteristics of responders (61%) and nonresponders (39%) were comparable except for larger QRS complex (172 ± 24 vs 160 ± 16 ms, p 3 remained an independent predictor at multivariate analysis. In patients with nonischemic origin of cardiomyopathy, the linear regression analysis documented a significant inverse relation between QRS duration and LVdys, as dyssynchrony progressively decreased as QRS widening increased (p = 0.006). This was not evident in patients with ischemic origin. In conclusion, in LBBB patients with nonischemic origin and marked QRS widening, the absence of LVdys may account for a lower response to CRT compared with patients with intermediate QRS widening.

Background: Although the majority of patients with Crohn’s disease (CD) are young, they are often seriously ill when surgery is required. The Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) is a risk prediction scoring system estimating 30-day complications. The primary endpoint was to evaluate POSSUM efficacy in this subgroup. The secondary endpoint was to determine any potential correlation between POSSUM, Harvey–Bradshaw Index (HBI), length of stay (LOS) and anastomotic leak. Methods: All patients affected by abdominal CD who underwent elective and emergency surgery from 2006 to 2011 were prospectively enrolled in the study. POSSUM expected morbidity and mortality were compared to the observed outcomes (O/E ratio). Logistic regression analysis was performed to evaluate POSSUM and HBI adequacy. Correlation between POSSUM, HBI, LOS and anastomotic leak was investigated with linear regression analysis. Results: One hundred twenty-three patients underwent abdominal surgery. The overall 30-day mortality rate estimated by the Portsmouth-POSSUM was 1.22% (95% confidence interval (CI) 0.4–3.6) while no deaths were observed (O/E = 0). The prediction regarding the post-operative complication rate was 22.04% (95% CI 11.1– 51.2) and the observed overall morbidity rate was 21.95% (O/E = 0.99). The mean HBI score was 6.85 while LOS was 9.4 days. POSSUM and HBI were found to be significant predictors of post-operative complications at the univariate logistic regression analysis (OR 1.17 95% CI 1.06–1.30 and OR 1.25 95% CI 1.04–1.49, respectively). Linear regression analysis showed a significant correlation between POSSUM, HBI and LOS. Conclusion: POSSUM is precise in predicting post-operative complications in patients with abdominal CD. POSSUM correlates with HBI.

AimsThis study compared the clinical, functional, and haemodynamic characteristics and current era survival of subgroups of patients with pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD): Eisenmenger syndrome (ES); PAH-CHD associated with systemic-to-pulmonary shunts (SPs); PAH with small defects (SDs); and PAH after defect correction (CDs).Methods and resultsData from consecutive PAH-CHD patients referred to our centre from 1 January 1998 to 31 May 2011 were collected. A contemporary group of idiopathic PAH patients was utilized for comparison. Treatment was per PAH guidelines, including combination therapy, with approved PAH-specific drugs. Survival was assessed with Kaplan-Meier analysis from the first invasive haemodynamic confirmation of PAH and compared across subgroups by log-rank test. Of 192 patients (mean age 41 ± 17 years; 61% female), 90 had ES (aged 41 ± 16 years); 48 SP (aged 47 ± 18 years); 10 SD (aged 25 ± 21 years); and 44 CD (aged 36 ± 17 years). Patients with ES had the highest baseline pulmonary vascular resistance and the lowest exercise capacity. Seventy-eight per cent were treated with approved PAH-specific drugs, and 44% were treated with combination therapy. Kaplan-Meier survival estimates (95% confidence interval) at 20 years for ES, SP, and CD were 87% (77-93%), 86% (60-96%), and 36% (12-72%, P = 0.0001 vs. ES; P = 0.004 vs. SP), respectively, and at 15 years for SD was 66% (16-91%, P = 0.015 vs. ES; P = 0.016 vs. SP). The survival of the 278 patients with idiopathic PAH appeared to be worse when compared with the PAH-CHD subgroups.ConclusionRelevant clinical, functional, haemodynamic, and survival differences were observed among subgroups. In particular, patients with CD and SD had the worst survival. These findings should be considered when planning medical or interventional treatment strategies in PAH-CHD patients.

Background Stroke is a rare but serious adverse event associated with percutaneous coronary intervention (PCI). However, the relative risk of stroke between stable patients undergoing a direct PCI strategy and those undergoing an initial optimal medical therapy (OMT) strategy has not been established yet. This study sought to investigate if, in patients with stable coronary artery disease (SCAD), an initial strategy PCI is associated with a higher risk of stroke than a strategy based on OMT alone. Methods We performed a meta-analysis of 6 contemporary randomized control trials in which 5673 patients with SCAD were randomized to initial PCI or OMT. Only trials with stent utilization more than 50% were included. Study endpoint was the rate of stroke during follow up. Results Mean age of patients ranged from 60 to 65 years and stent utilization ranged from 72% to 100%. Rate of stroke was 2.0% at a weighted mean follow up of 55.3 months. On pooled analysis, the risk of stroke was similar between patients undergoing a PCI plus OMT and those receiving only OMT (2.2% vs. 1.8%, OR on fixed effect = 1.24 95%CI: 0.85–1.79). There was no heterogeneity among the studies (I2 = 0.0%, P = 0.15). On sensitivity analysis after removing each individual study the pooled effect estimate remains unchanged. Conclusions In patients with SCAD an initial strategy based on a direct PCI is not associated with an increased risk of stroke during long-term follow up compared to an initial strategy based on OMT alone.