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Objectives: Atrial arrhythmias after heart transplantation have rarely been investigated. The aim of this study is to assess incidence, type and predictors of atrial arrhythmias during a long-term follow-up in a large population of heart-transplanted patients., Methods: Consecutive patients undergone to heart transplantation at our Centre from 1990 to 2017 were enrolled. All documented atrial arrhythmias were systematically reviewed during a long-term follow-up after heart transplantation. Atrial fibrillation (AF), atrial flutter and tachycardias were defined according to current guidelines., Results: Overall, 364 patients were included and followed for 120 ± 70 months. During the follow-up period 108 (29.7%) patients died and 3 (0.8%) underwent re-transplantation. Sinus rhythm was present in 355 (97.5%) patients. Nine patients had persistent atrial arrhythmias: 8 (2.2%) presented atypical flutter and one (0.3%) patient AF. Paroxysmal sustained arrhythmias were detected in 42 (11.5%) patients, always atrial flutters. At univariate analysis several echocardiographic (left ventricular end-diastolic diameter, TEI index, mitral and tricuspid regurgitation grade) hemodynamic (systolic and diastolic pulmonary pressure, capillary wedge pressure) and clinical (dyslipidaemia, weight, pacemaker implantation) parameters related to higher incidence of atrial arrhythmias., Conclusion: Persistent atrial arrhythmias, and most of all AF, are rare among heart transplantation carriers, despite substantial comorbidities resulting in significant mortality. It can be speculated that the lesion set provided by the surgical technique, a complete and transmural electrical isolation of the posterior left atrium wall, represents an effective lesion set to prevent persistent AF., Competing Interests: Declaration of competing interest The authors have no potential conflicts of interest to disclose., (Copyright © 2020. Published by Elsevier B.V.)

Aims: Novel therapies are needed for recurrent pericarditis, particularly when corticosteroid dependent and colchicine resistant. Based on limited data, interleukin-1 blockade with anakinra may be beneficial. The aim of this multicentre registry was to evaluate the broader effectiveness and safety of anakinra in a 'real world' population., Methods and Results: This registry enrolled consecutive patients with recurrent pericarditis who were corticosteroid dependent and colchicine resistant and treated with anakinra. The primary outcome was the pericarditis recurrence rate after treatment. Secondary outcomes included emergency department visits, hospitalisations, corticosteroid use and adverse events. Among 224 patients (46 ± 14 years old, 63% women, 75% idiopathic), the median duration of disease was 17 months (interquartile range 9-33). Most patients had elevated C-reactive protein (91%) and pericardial effusion (88%). After a median treatment of 6 months (3-12), pericarditis recurrences were reduced six-fold (2.33-0.39 per patient per year), emergency department admissions were reduced 11-fold (1.08-0.10 per patient per year), hospitalisations were reduced seven-fold (0.99-0.13 per patient per year). Corticosteroid use was decreased by anakinra (respectively from 80% to 27%; P  < 0.001). No serious adverse events occurred; adverse events consisted mostly of transient skin reactions (38%) at the injection site. Adverse events led to discontinuation in 3%. A full-dose treatment duration of over 3 months followed by a tapering period of over 3 months were the therapeutic schemes associated with a lower risk of recurrence., Conclusion: In patients with recurrent pericarditis, anakinra appears efficacious and safe in reducing recurrences, emergency department admissions and hospitalisations.

Aims: To develop and validate a multi-parametric practical score to predict the probability of survival to hospital admission of an out-of-hospital cardiac arrest (OHCA) victim by using Utstein Style-based variables., Methods: All consecutive OHCA cases occurring from 2015 to 2017 in two regions, Pavia Province (Italy) and Canton Ticino (Switzerland) were included. We used random effect logistic regression to model survival to hospital admission after an OHCA. We computed the model area under the ROC curve (AUC ROC) for discrimination and we performed both internal and external validation by considering all OHCAs occurring in the aforementioned regions in 2018. The Utstein-Based ROSC (UB-ROSC) score was derived by using the coefficients estimated in the regression model. The score value was obtained adding the pertinent score components calculated for each variable. The score was then plotted against the probability of survival to hospital admission., Results: 1962 OHCAs were included (62% male, mean age 73 ± 16 years). Age, aetiology, location, witnessed OHCA, bystander CPR, EMS arrival time and shockable rhythm were independently associated with survival to hospital admission. The model showed excellent discrimination (AUC 0.83, 95%CI 0.81-0.85) for predicting survival to hospital admission, also at internal cross-validation (AUC 0.82, 95%CI 0.80-0.84). The model maintained good discrimination after external validation by using the 2018 OHCA cohort (AUC 0.77, 95%CI 0.74-0.80)., Conclusions: UB-ROSC score is a novel score that predicts the probability of survival to hospital admission of an OHCA victim. UB-ROSC shall help in setting realistic expectations about sustained ROSC achievement during resuscitation manoeuvres., Competing Interests: Declaration of competing interest The authors report no conflicts of interest related specifically to this manuscript., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The protective role of high HDL cholesterol levels against cardiovascular diseases has been recently questioned. Limited data are available on this specific topic in patients with type 2 diabetes mellitus (T2DM). We aimed to evaluate the association of HDL cholesterol concentrations with all-cause and cause-specific mortality in a historical cohort of T2DM patients with 14 years of follow-up., Methods: This is a retrospective population-based cohort study involving 2113 T2DM patients attending the Diabetic Clinic of Asti. Survival analyses were performed to assess hazard ratios for overall and specific-cause mortality by HDL cholesterol tertiles, using the middle HDL cholesterol tertile as a reference., Results: The mean age was 66 ± 11 years; 51.4% of patients had low HDL-cholesterol levels. After a 14-year follow-up, 973/2112 patients had died (46.1%). The HDL cholesterol tertile cut-off points were 37.5 and 47.5 mg/dL (males) and 41.5 and 52.0 mg/dL (females). No associations between lower and upper HDL cholesterol tertiles respectively and all-cause (HR = 1.12; 95% CI 0.96-1.32; HR = 1.11; 0.95-1.30), cardiovascular (HR = 0.97; 0.77-1.23; HR = 0.94; 0.75-1.18) or cancer (HR = 0.92; 0.67-1.25; HR = 0.89; 0.66-1.21) mortality were found. A significantly increased risk for infectious disease death was found both in the lower (HR = 2.62; 1.44-4.74) and the upper HDL-cholesterol tertiles (HR = 2.05; 1.09-3.85) when compared to the reference. Individuals in the upper tertile showed an increased risk for mortality due to diabetes-related causes (HR = 1.87; 1.10-3.15)., Conclusions: Our results corroborate the hypothesis that HDL cholesterol levels are nonprotective in T2DM patients. The U-shaped association between HDL-cholesterol levels and mortality associated with infectious diseases should be verified by further studies.

Pulmonary vein isolation is the cornerstone of atrial fibrillation (AF) ablation. Radiofrequency (RF) represents a standard of care for pulmonary vein isolation, whereas cryoballoon (CB) ablation has emerged as a valid alternative. The aim of our meta-analysis was to explore the efficacy and safety of CB compared with RF as first ablation procedure for AF. We searched the literature for studies that investigated this issue. The primary efficacy outcome was AF recurrence. The safety outcomes were: pericardial effusion, cardiac tamponade, phrenic nerve palsy, vascular complications, and major bleedings. Fourteen randomized controlled studies and 34 observational studies were included in the analysis. A total of 7,951 patients underwent CB ablation, whereas 9,641 received RF ablation. Mean follow-up was 14 ± 7 months. Overall, CB reduced the incidence of AF recurrence compared with RF ablation (relative risk [RR] 0.86; 95% confidence interval [CI] 0.78 to 0.94; p = 0.001), and this result was consistent across different study design and AF type. CB had a significantly higher rate of phrenic nerve palsy, whereas it was related to a lower incidence of pericardial effusion, cardiac tamponade (RR 0.58; 95% CI 0.38 to 0.88; p = 0.011) and vascular complications (RR 0.61; 95% CI 0.48 to 0.77; p <0.001) compared with RF. There was no significant difference in major bleedings between the 2 strategies. CB ablation had a shorter procedural time compared with RF (mean difference -20.76 minutes; p <0.001). In conclusion, considered its efficacy/safety profile and short procedural time, CB ablation represents the preferable option for first AF ablation procedure., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Neoplastic pericardial effusion is a common and serious manifestation of advanced malignancies. Lung and breast carcinoma, haematological malignancies, and gastrointestinal cancer are the most common types of cancer involving the pericardium. Pericardial involvement in neoplasia may arise from several different pathophysiological mechanisms and may be manifested by pericardial effusion with or without tamponade, effusive-constrictive pericarditis and constrictive pericarditis. Management of these patients is a complex multidisciplinary problem, affected by clinical status and prognosis of patients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Biochemical analysis of pericardial fluid (PF) is commonly performed for the initial assessment of PF, and the results are usually interpreted according to Light's traditional criteria for the differential diagnosis of transudates versus exudates. However, Light's criteria have been formulated for the biochemical analysis of pleural fluid. The aim of the present paper is to evaluate the normal composition of PF in candidates for cardiac surgery., Methods: Cohort study with analysis of PF from candidates for cardiac surgery. Exclusion criteria were previous pericardial disease or cardiac surgery, prior myocardial infarction within 3 months, systemic disease (eg, systemic inflammatory diseases, uremia) or drug with potentiality to affect the pericardium., Results: Fifty patients (mean age was 67 years; 95% CI 64 to 71, 29 males, 58.0%) were included in the present analysis. Levels of small molecules were similar in blood and PF. Total proteins in PF was, on average, 0.5 times lower than corresponding plasma levels (p=0.041), while the level of pericardial lactate dehydrogenase was, on average, 1.06 times higher than plasma (p=0.55). Moreover, mononuclear cells were more concentrated in PF than plasma (p=0.17). Traditional Light's criteria misclassified all PFs as exudates., Conclusions: Traditional Light's criteria misclassified normal PFs in candidates for cardiac surgery as exudates. This study suggests their futility for the biochemical analysis of PF in clinical practice., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: There are limited data regarding the impact of final kissing balloon (FKI) in patients treated with percutaneous coronary intervention using ultrathin stents in left main or bifurcations., Methods: All patients undergoing left main or bifurcations percutaneous coronary intervention enrolled in the RAIN registry (Very Thin Stents for Patients With MAIN or BiF in Real Life: The RAIN, a Multicenter Study) evaluating ultrathin stents were included. Major adverse cardiac event (a composite of all-cause death, myocardial infarction, target lesion revascularization, and stent thrombosis) was the primary end point, while its components, along with target vessel revascularization, were the secondary end points. The main analysis was performed comparing patients with and without FKI after adjustment with inverse probability of treatment weighting. Subgroup analyses were performed according to FKI (short [<3 mm] versus long overlap), strategy (provisional versus 2-stent), routine versus bail-out FKI, and the use of imaging and proximal optimization technique., Results: Two thousand seven hundred forty-two patients were included. At 16 months (8-20) follow-up, inverse probability of treatment weighting adjusted rates of major adverse cardiac event were similar between FKI and no-FKI group (15.1% versus 15.5%; P =0.967), this result did not change with use of imaging, proximal optimization technique, or routine versus bail-out FKI. In the 2-stent subgroup, FKI was associated with lower rates of target vessel revascularization (7.8% versus 15.9%; P =0.030) and target lesion revascularization (7.3% versus 15.2%; P =0.032). Short overlap FKI was associated with a lower rate of target lesion revascularization compared with no FKI (2.6% versus 5.4%; P =0.034), while long overlap was not (6.8% versus 5.4%; P =0.567)., Conclusions: In patients with bifurcations or unprotected left main treated with ultrathin stents, short overlap FKI is associated with less restenosis. In a 2-stent strategy, FKI was associated with less target vessel revascularization and restenosis. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03544294.

Incidence and predictors of adverse events after dual antiplatelet therapy (DAPT) cessation in patients treated with thin stents (<100 microns) in unprotected left main (ULM) or coronary bifurcation remain undefined. All consecutive patients presenting with a critical lesion of an ULM or involving a main coronary bifurcation who were treated with very thin strut stents were included. MACE (a composite end point of cardiovascular death, myocardial infarction [MI], target lesion revascularization [TLR], and stent thrombosis [ST]) was the primary endpoint, whereas target vessel revascularization (TVR) was the secondary endpoint, with particular attention to type and occurrence of ST and occurrence of ST, CV death, and MI during DAPT or after DAPT discontinuation. All analyses were performed according to length of DAPT dividing the patients in 3 groups: Short DAPT (3-months), intermediate DAPT (3 to 12 months), and long DAPT (12-months). A total of 117 patients were discharged with an indication for DAPT ≤3 months (median 1: 1 to 2.5), 200 for DAPT between 3 and 12 months (median 8: 7 to 10), and 1,958 with 12 months DAPT. After 12.8 months (8 to 20), MACE was significantly higher in the 3-month group compared with 3 to 12 and 12-month groups (9.4% vs 4.0% vs 7.2%, p ≤0.001), mainly driven by MI (4.4% vs 1.5% vs 3%, p ≤0.001) and overall ST (4.3% vs 1.5% vs 1.8%, p ≤0.001). Independent predictors of MACE were low GFR and a 2 stent strategy. Independent predictors of ST were DAPT duration <3 months and the use of a 2-stent strategy. In conclusion, even stents with very thin strut when implanted in real-life ULM or coronary bifurcation patients discharged with short DAPT have a relevant risk of ST, which remains high although not significant after DAPT cessation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Aims: A large trial established the favourable clinical profile of a new polymer-free biolimus A9-eluting stent (PF-BES) with a one-month dual antiplatelet therapy (DAPT) regimen in patients at high bleeding risk (HBR). We aimed to evaluate the real-world patterns of indications, DAPT strategies and outcomes for the PF-BES following this evidence., Methods and Results: CHANCE is a multicentre registry including all patients who underwent percutaneous coronary intervention (PCI) with at least one PF-BES. The reasons for the PF-BES PCI and planned antithrombotic regimens were collected. Primary outcomes were the 390-day Kaplan-Meier estimates of patient-oriented and device-oriented composite endpoints (POCE: death, myocardial infarction [MI] or target vessel revascularisation [TVR]; DOCE: cardiac death, target vessel MI or ischaemia-driven target lesion revascularisation [ID-TLR]). Between January 2016 and July 2018, 858 patients (age 74±10 years, 64.6% male, 58.7% acute coronary syndrome presentation) underwent PF-BES PCI. The main reasons for the physicians' choice of PF-BES reflected a perceived HBR in 77.7% of patients. One-month DAPT was planned in 40.3% of patients. At 390-day follow-up (median 340 days, interquartile range: 187-390 days), the estimated incidence of POCE was 13.1% (any MI 3.7%, any TVR 3.4%) and of DOCE was 7.1% (TV-MI 3.6%, ID-TLR 1.4%), while the 390-day estimate of any bleeding event was 11.1% (BARC 3-5 bleeding 3.0%)., Conclusions: In a large all-comers registry, PF-BES was used mostly in HBR patients, frequently followed by a very short DAPT regimen. The reported outcomes suggest a favourable safety and efficacy profile for the PF-BES in a real-world clinical setting. ClinicalTrials.gov identifier: NCT03622203.

Aims: The aim of the present study was to investigate the impact of aspirin on prognosis in takotsubo syndrome (TTS)., Methods and Results: Patients from the International Takotsubo (InterTAK) Registry were categorized into two groups based on aspirin prescription at discharge. A comparison of clinical outcomes between groups was performed using an adjusted analysis with propensity score (PS) stratification; results from the unadjusted analysis were also reported to note the effect of the PS adjustment. Major adverse cardiac and cerebrovascular events (MACCE: a composite of death, myocardial infarction, TTS recurrence, stroke or transient ischaemic attack) were assessed at 30-day and 5-year follow-up. A total of 1533 TTS patients with known status regarding aspirin prescription at discharge were included. According to the adjusted analysis based on PS stratification, aspirin was not associated with a lower hazard of MACCE at 30-day [hazard ratio (HR) 1.24, 95% confidence interval (CI) 0.50-3.04, P = 0.64] or 5-year follow-up (HR 1.11, 95% CI 0.78-1.58, P = 0.58). These results were confirmed by sensitivity analyses performed with alternative PS-based methods, i.e. covariate adjustment and inverse probability of treatment weighting., Conclusion: In the present study, no association was found between aspirin use in TTS patients and a reduced risk of MACCE at 30-day and 5-year follow-up. These findings should be confirmed in adequately powered randomized controlled trials. ClinicalTrials.gov Identifier: NCT01947621., (© 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology.)

Background: The risk of recurrent ischemia and bleeding after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) may vary during the first year of follow-up according to clinical presentation, and medical and interventional strategies., Methods: BleeMACS and RENAMI are 2 multicenter registries enrolling patients with ACS treated with PCI and clopidogrel, prasugrel, or ticagrelor. The average daily ischemic and bleeding risks (ADIR and ADBR) in the first year after PCI were the primary end points. The difference between ADBR and ADIR was calculated to estimate the potential excess of bleeding/ischemic events in a given period or specific subgroup., Results: A total of 19,826 patients were included. Overall, in the first year after PCI, the ADBR was 0.008085%, whereas ADIR was 0.008017% (P = .886). In the first 2 weeks ADIR was higher than ADBR (P = .013), especially in patients with ST-segment elevation myocardial infarction or incomplete revascularization. ADIR continued to be, albeit non-significantly, greater than ADBR up to the third month, whereas ADBR became higher, although not significantly, afterward. Patients with incomplete revascularization had an excess in ischemic risk (P = .003), whereas non-ST-segment elevation ACS patients and those on ticagrelor had an excess of bleeding (P = .012 and P = .022, respectively)., Conclusions: In unselected ACS patients, ADIR and ADBR occurred at similar rates within 1 year after PCI. ADIR was greater than ADBR in the first 2 weeks, especially in ST-segment elevation myocardial infarction patients and those with incomplete revascularization. In the first year, ADIR was higher than ADBR in patients with incomplete revascularization, whereas ADBR was higher in non-ST-segment elevation ACS patients and in those discharged on ticagrelor., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Cardiac magnetic resonance (CMR) offers the capability to objectively detect pericarditis by identifying pericardial thickening, edema/inflammation by Short-TI Inversion Recovery-T2 weighted (STIR-T2w) imaging, edema/inflammation or fibrosis by late gadolinium enhancement (LGE), and presence of pericardial effusion. This is especially helpful for the diagnosis of recurrent pericarditis. Aim of the present paper is to assess the diagnostic accuracy of CMR findings as well as their potential prognostic value for the diagnosis of recurrent pericarditis. Multicenter cohort study of consecutive patients with recurrent pericarditis evaluated by CMR. We included 128 consecutive cases (60 males, 47%; mean age 48 ± 14 years). CMR was performed at a mean time of 12 days (95% confidence interval 15 to 21) after the clinical diagnosis. We evaluated the diagnostic accuracy and areas under the receiver operating characteristic (ROC) curve for CMR diagnostic criteria and complications (additional recurrences, cardiac tamponade, and constrictive pericarditis). Areas under the ROC curve were respectively 64% for pericardial thickening, 84% for pericardial edema, 82% for pericardial LGE, and 71% for pericardial effusion. After a mean follow-up of 34 months, recurrences occurred in 52% of patients, tamponade in 6%, and constrictive pericarditis in 11%. Using a multivariable Cox model, elevation of CRP and presence of CMR pericardial thickening were predictors of adverse events, whereas the presence of CMR LGE was associated with a lower risk. The prognostic model for adverse events using gender, age, CRP level, and all CMR variables showed a C-index of 0.84. In conclusion, CMR findings show high diagnostic accuracy and may help identifying patients at higher risk of complications., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Randomized controlled trials (RCT) of psychotherapeutic interventions have addressed depression and demoralization associated with acute coronary syndromes (ACS). The present trial introduces psychological well-being, an increasingly recognized factor in cardiovascular health, as a therapeutic target., Objective: This study was designed to determine whether the sequential combination of cognitive-behavioral therapy (CBT) and well-being therapy (WBT) may yield more favorable outcomes than an active control group (clinical management; CM) and to identify subgroups of patients at greater risk for cardiac negative outcomes., Methods: This multicenter RCT comparedCBT/WBT sequential combination versus CM, with up to 30 months of follow-up. One hundred consecutive depressed and/or demoralized patients (out of 740 initially screened by cardiologists after a first episode of ACS) were randomized to CBT/WBT associated with lifestyle suggestions (n = 50) and CM (n = 50). The main outcome measures included: severity of depressive symptoms according to the Clinical Interview for Depression, changes in subclinical psychological distress, well-being, and biomarkers, and medical complications and events., Results: CBT/WBT sequential combination was associated with a significant improvement in depressive symptoms compared to CM. In both groups, the benefits persisted at follow-up, even though the differences faded. Treatment was also related to a significant amelioration of biomarkers (platelet count, HDL, and D-dimer), whereas the 2 groups showed similar frequencies of adverse cardiac events., Conclusions: Addressing psychological well-being in the psychotherapeutic approach to ACS patients with depressive symptoms was found to entail important clinical benefits. It is argued that lifestyle changes geared toward cardiovascular health may be facilitated by a personalized approach that targets well-being., (© 2020 S. Karger AG, Basel.)

Aims: The aim of the present study was to establish the safety and efficacy profile of prasugrel and ticagrelor in real-life acute coronary syndrome (ACS) patients with renal dysfunction., Methods and Results: All consecutive patients from RENAMI (REgistry of New Antiplatelets in patients with Myocardial Infarction) and BLEEMACS (Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome) registries were stratified according to estimated glomerular filtration rate (eGFR) lower or greater than 60 mL/min/1.73 m2. Death and myocardial infarction (MI) were the primary efficacy endpoints. Major bleedings (MBs), defined as Bleeding Academic Research Consortium bleeding types 3 to 5, constituted the safety endpoint. A total of 19 255 patients were enrolled. Mean age was 63 ± 12; 14 892 (77.3%) were males. A total of 2490 (12.9%) patients had chronic kidney disease (CKD), defined as eGFR <60 mL/min/1.73 m2. Mean follow-up was 13 ± 5 months. Mortality was significantly higher in CKD patients (9.4% vs. 2.6%, P < 0.0001), as well as the incidence of reinfarction (5.8% vs. 2.9%, P < 0.0001) and MB (5.7% vs. 3%, P < 0.0001). At Cox multivariable analysis, potent P2Y12 inhibitors significantly reduced the mortality rate [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.54-0.96; P = 0.006] and the risk of reinfarction (HR 0.53, 95% CI 0.30-0.95; P = 0.033) in CKD patients as compared to clopidogrel. The reduction of risk of reinfarction was confirmed in patients with preserved renal function. Potent P2Y12 inhibitors did not increase the risk of MB in CKD patients (HR 1.00, 95% CI 0.59-1.68; P = 0.985)., Conclusion: In ACS patients with CKD, prasugrel and ticagrelor are associated with lower risk of death and recurrent MI without increasing the risk of MB., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Introduction : Acute pericarditis is frequently complicated with recurrences, which represent a diagnostic and therapeutic challenge for the physician, a bothersome trouble for patients. An incorrect treatment of pericarditis may cause further recurrence of symptoms, while an incorrect diagnosis may cause either a prolonged symptoms course with a possible risk of chronic constriction, or useless and potentially harmful treatments. Areas covered : This review will focus on the most useful and recent diagnostic tools for recurrent pericarditis. Medline/Pubmed Library were screened with specific key search: 'recurrent AND pericarditis'. The research was restricted to papers published in the last 5 years (2015-2019) and papers in English language, in order to appraise the latest advances in diagnostic assessment. Expert opinion : An accurate diagnosis of recurrent pericarditis is critical to provide timely and appropriate treatment of symptoms and prevention of further episodes. Diagnosis is made in case of recurrent symptoms associated with a documented evidence of pericardial inflammation. Further studies are needed to develop newer diagnostic tools aimed at identification of a predominant auto-inflammatory of auto-immune mechanism, which is essential to tailor the treatment.

The NeoChord procedure is an innovative microinvasive, transventricular, beating-heart chordal replacement technique for patients with severe degenerative mitral valve regurgitation resulting from prolapsed or flail leaflets. Use of three-dimensional (3D) transoesophageal echocardiographic imaging is crucial to the physician operator for device navigation during the procedure and to assess the functional results of the repair at the end of the procedure. Photo-realistic, 3D rendering techniques have been recently developed for medical use. Philips TrueVue (Philips Healthcare, Eindhoven, NL) is a photo-realism technique that employs the use of a virtual light source that simulates the interaction of light on 3-dimensional surfaces. Use of photo-realism techniques, in conjunction with 3D echocardiography, improves the visualization of morphological characteristics of the mitral valve before, during, and after beating-heart mitral valve repair procedures., (© 2019 Wiley Periodicals, Inc.)

Background and O bjectives: Surgical atrial fibrillation (AF) ablation concomitant to minimally invasive mitral valve repair has been proven to offer improved short- and long-term sinus rhythm (SR) maintenance compared to mitral valve surgery only. The objective of the present study was to explore, by thorough echocardiographic assessment, long-term morphological and functional left atrial (LA) outcomes after this combined surgical procedure. Materials and M ethods : From October 2006 to November 2015, 48 patients underwent minimally invasive mitral valve repair and concomitant surgical AF cryoablation. Results: After 3.8 ± 2.2 years, 30 (71.4%) of those completing the follow-up ( n = 42, 87.5%) presented SR. During follow-up, four (9.5%) patients suffered from cerebrovascular accidents and two of these subjects had a long-standing persistent AF relapse and were in AF at the time of the event, while the other two were in SR. An echocardiographic study focused on LA characteristics was performed in 29 patients (69.0%). Atrial morphology and function (e.g., maximal LA volume indexed to body surface area and total LA emptying fraction derived from volumes) in patients with stable SR (60.6 ± 13.1 mL/mq and 25.1 ± 7.3%) were significantly better than in those with AF relapses (76.8 ± 16.2 mL/mq and 17.5 ± 7.4%; respectively, p = 0.008 and p = 0.015). At follow-up, patients who suffered from ischemic cerebral events had maximal LA volume indexed to body surface area 61 ± 17.8 mL/mq, with total LA emptying fraction derived from volumes 23.6 ± 13.7%; patients with strokes in SR showed very enlarged LA volume (>70 mL/mq). Conclusions : AF cryoablation concomitant with minimally invasive mitral valve repair provides a high rate of SR maintenance and this relates to improved long-term morphological and functional LA outcomes. Further prospective studies are needed to define the cut-off values determining an increase in the risk for thromboembolic complications in patients with restored stable SR., Competing Interests: The authors declare no conflict of interest.

The real prognostic impact of MitraClip in patients with significant functional mitral regurgitation (FMR) and left ventricular (LV) dysfunction remains to be elucidated. Two randomized controlled trials (RCTs) with conflicting results have been recently published. We conducted a comprehensive meta-analysis of all RCTs and adjusted observational studies to evaluate the clinical impact of percutaneous mitral valve repair when compared with optimal medical therapy (OMT) alone, in patients with symptomatic FMR and LV dysfunction. Death from any cause and heart failure rehospitalizations at the longest available follow-up were the primary endpoints. Cardiac death, one year and short-term death were the secondary ones. 2255 patients (1207 for MitraClip and 1048 for OMT-only) from 8 studies (2 RCTs and 6 observational studies) were included. At a median (mid-term) follow-up of 438 days (IQR 360-625) MitraClip was associated with a significant reduction of all-cause death (odds Ratio [OR] 0.55, 95%CI 0.41-0.73, p < 0.001; [ORadj] 0.66, 95%CI 0.49-0.90, p = 0.009) and rehospitalization (OR 0.49, 95%CI 0.24-1.00, p = 0.05 and ORadj 0.63, 95%CI 0.43-0.94, p = 0.02). At one year, adjusted analysis demonstrated a trend favoring the experimental cohort (ORadj 0.73, 95%CI 0.53-1.02, p = 0.07). Meta-regression suggested that benefit of MitraClip on mid-term survival persists even after accounting for the prevalence of implanted CRT, burden of comorbidities, NYHA class, cardiomyopathy etiology and LV function and dimensions. In conclusion, MitraClip for FMR in patients with LV dysfunction is associated with a considerable reduction of death and HF hospitalization at mid-term follow-up. Further ongoing RCTs are needed to strengthen present results., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Atrial Fibrillation (AF) may be diagnosed due to symptoms, or it may be found as an incidental electrocardiogram (ECG) finding, or by implanted devices recordings in asymptomatic patients. While anticoagulation, according to individual risk profile, has proven definitely beneficial in terms of prognosis, rhythm control strategies only demonstrated consistent benefits in terms of quality of life. In fact, evidence collected by observational data showed significant benefits in terms of mortality, stroke incidence, and prevention of cognitive impairment for patients referred to AF catheter ablation compared to those medically treated, however randomized trials failed to confirm such results. The aims of this review are to summarize current evidence regarding the treatment specifically of subclinical and asymptomatic AF, to discuss potential benefits of rhythm control therapy, and to highlight unclear areas.

Background: There is lack of noninvasive indices to detail the right side cardiovascular physiology. Total isovolumic time (tIVT) is a sensitive marker of left ventricular electromechanical efficiency and systolic-diastolic interaction. The aim of the study was to evaluate normal reference value of the right ventricular tIVT with increasing age., Methods and Results: One hundred and eighty-one healthy volunteers (51% male) underwent transthoracic echocardiography. The population was divided into four categories according to age: A < 30 years; B 30-39 years; C 40-49 years; and C ≥ 50 years old. tIVT was computed in seconds/minutes as: 60 - (tET + tFT). tET and tFT are the total ejection and filling time adjusted by the heart rate, measured, respectively, from the onset to the end of the right ventricle (RV) forward flow through the pulmonary valve and from the onset of the E-wave and the end of the A-wave at the level of the tricuspid valve. The mean RV tIVT was 7 ± 1.1 s/min and increased significantly with age, from a 3.4 to 9.7 s/min(P < 0.0001). Significant correlation was found between tIVT and trans-tricuspid E/E' (P < 0.0001; 0.78 (95% CI: 0.715-0.831) while weaker between tIVT and E/A (P = 0.001; -0.283 95% CI: -0.413 to -0.143)., Conclusion: The normal values of RV tIVT increase with age and correlate significantly with Doppler diastolic parameters., (© 2019 Wiley Periodicals, Inc.)

Aims: To systematically review literature comparing bare metal stent (BMS) to drug-eluting stent (DES) in end-stage renal disease (ESRD) patients on dialysis. ESRD patients on dialysis often suffer from accelerated atherosclerosis and higher rate of stent-related complications including major adverse cardiovascular events. Because dialysis usually qualifies ineligibility for randomized clinical trials, an evidenced-based stent choice for these patients is scarce., Methods: PUBMED, CINHAL, COCHRANE, EMBASE and WEB OF SCIENCE were searched for studies comparing BMS vs. DES outcome in ESRD patients on dialysis., Results: Twenty studies including 64 232 patients were considered. The use of DES was significantly associated with a reduction in all-cause mortality [odds ratio (OR) 0.83, 95% confidence interval (CI) 0.76-0.89], death from a cardiovascular cause (OR 0.80, 95% CI 0.76-0.84) and target lesion revascularization/target vessel revascularization (OR 0.73, 95% CI 0.53-1.00). No significant difference was found in stent thrombosis (OR 1.08, 95% CI 0.50-2.33) and myocardial infarction incidence (OR 0.91, 95% CI 0.69-1.20)., Conclusions: Our meta-analysis shows a significant reduction in all-cause and cardiovascular mortality with the use of DES over BMS in dialyzed patients. Despite the lack of randomized studies, systematic use of DES in these high-risk patients should thus reasonably be considered as a first option in percutaneous coronary intervention candidates.

Left cardiac sympathetic denervation (LCSD) is a surgical antiadrenergic intervention with a strong antiarrhythmic effect, supported by preclinical as well as clinical data. The mechanism of action of LCSD in structurally normal hearts with increased arrhythmic susceptibility (such as those of patients with channelopathies) is not limited to the antagonism of acute catecholamines release in the heart. LCSD also conveys a strong anti-fibrillatory action that was first demonstrated over 40 years ago and provides the rationale for its use in almost any cardiac condition at increased risk of ventricular fibrillation. The molecular mechanisms involved in the final antiarrhythmic effect of LCSD turned out to be much broader than anticipated. Beside the vagotonic effect at different levels of the neuraxis, other new mechanisms have been recently proposed, such as the antagonism of neuronal remodeling, the antagonism of neuropeptide Y effects, and the correction of neuronal nitric oxide synthase (nNOS) imbalance. The beneficial effects of LCSD have never been associated with a detectable deterioration of cardiac performance. Finally, patients express a high degree of satisfaction with the procedure. In this review, we focus on the rationale, results and our personal approach to LCSD in patients with channelopathies such as long QT syndrome and catecholaminergic polymorphic ventricular tachycardia.

Background and Aims: There is contrasting evidence regarding the optimal antithrombotic regimen after percutaneous coronary stent implantation in patients on oral anticoagulants. A systematic review and meta-analysis was performed to explore the comparative efficacy and safety of dual (an antiplatelet plus an oral anticoagulant) versus triple therapy (dual antiplatelet therapy plus an oral anticoagulant)., Methods: We searched the literature for randomized controlled trials (RCTs) or observational studies (OSs) addressing this issue. The efficacy outcomes were all-cause mortality, cardiovascular mortality, myocardial infarction and stent thrombosis. The safety outcomes were major bleeding events and all bleeding events. The analyses were stratified by type of anticoagulant and of antiplatelet used in dual therapy., Results: Four RCTs and ten OSs met our inclusion criteria including a total of 10,126 patients. 5671 patients received triple therapy whereas 4455 received dual therapy. Median follow up was 12 months. There was no difference between dual therapy and triple therapy regarding efficacy outcomes. Dual therapy significantly reduced the risk of major bleeding (RR 0.66; CI 95% 0.52-0.83; P = 0.0005) and of all bleeding events (RR 0.67, CI 95% 0.55-0.80; P < 0.0001). The effect was consistent regardless of the type of antiplatelet and anticoagulant used in dual therapy., Conclusion: Dual antithrombotic therapy after coronary stenting in anticoagulated patients significantly reduces bleeding events compared with triple therapy. Dual therapy might be considered in this setting especially when bleeding risk outweighs ischemic risk, although our study was not sufficiently powered to detect a difference in ischemic endpoints., (Copyright © 2018. Published by Elsevier B.V.)

Background: Patients with coronary heart disease (CHD) and survivors of acute coronary syndrome (ACS) are at very high risk for adverse cardiovascular events. Lowering low-density lipoprotein cholesterol (LDL-C) can reduce the risk, with effective lipid-lowering therapy (LLT) readily available; however, dyslipidemia remains prevalent throughout Europe., Design: The observational Dyslipidemia International Study II (DYSIS II) aimed to identify unmet treatment needs in adult ACS and CHD patients. Data for the seven participating European countries are presented herein., Methods: The study was carried out from December 2012 to November 2014. Use of LLT and attainment of European-guideline-recommended LDL-C targets were assessed. For ACS patients, changes in lipid levels and LLT were evaluated 4 months post-hospitalization., Results: Of the 4344 patients enrolled, 2946 were attending a physician visit for the assessment of stable CHD, while 1398 had been hospitalized for an ACS event. In both patient sets, mean LDL-C levels were high (89.5 and 112.5 mg/dl, respectively) and <70 mg/dl target attainment extremely poor. The mean daily statin dosage (normalized to atorvastatin potency) was 27 ± 20 mg for CHD and 22 ± 17 mg for ACS patients. Treatment was intensified slightly for ACS subjects after hospitalization, with the dosage reaching 35 ± 24 mg/day. LDL-C target attainment was higher by the end of the 4-month follow up (30.9% and 41.5% for patients on LLT and without LLT at baseline, respectively; p < 0.05)., Conclusion: Elevated blood cholesterol levels are highly prevalent across Europe, with low numbers of coronary patients reaching their recommended LDL-C target. While use of LLT is widespread, there is significant scope for intensifying treatment.

Aims: About one-third of ischemic stroke are cryptogenic. Paradoxical embolism through patent foramen ovale (PFO) has been identified as a possible cause of cryptogenic stroke. Therefore, PFO closure has been considered for secondary prevention of cryptogenic stroke. However, randomized clinical trials (RCTs) comparing PFO closure versus medical therapy led to conflicting results. Our objectives were to examine if PFO closure is superior to medical therapy alone for secondary prevention of cryptogenic stroke and to investigate whether PFO closure is associated with an increased incidence of atrial fibrillation/atrial flutter (AFL)., Methods: The authors systematically searched MEDLINE for RCTs that compared PFO closure with medical therapy. Efficacy outcome was cerebrovascular event (CVE) recurrence and safety outcome was new-onset atrial fibrillation/AFL. The outcomes of interest were investigated according to device type with subgroup analyses and meta-regression., Results: The authors included eight RCTs constituting 4114 patients. Patients who underwent PFO closure had a lower risk of CVE recurrence compared with medically treated patients [relative risk (RR): 0.56; 95% confidence interval (CI) 0.40-0.80; P = 0.001; I = 30%]. This protective effect was consistent across the different device types. Patients who underwent PFO closure developed more frequently atrial fibrillation/AFL (RR 4.96; 95% CI 2.74-8.99; P < 0.00001; I = 0%), which was mainly transient and within 1 month. Atrial fibrillation/AFL risk was consistent according to device types, although marginally significant in the Amplatzer subgroup., Conclusion: PFO closure might have a role in secondary CVE prevention of patients with PFO and cryptogenic stroke. However, it is associated with an increased incidence of new-onset atrial fibrillation/AFL especially within 1 month.

Aims To compare clinical outcome in Chronic kidney disease (CKD) patients receiving coronary stents according to stent type BMS versus DES and 1st generation versus 2nd generation DES. Methods and Results PubMed, Cinhal, Cochrane, Embase, and Web of Science were searched for studies including CKD patients. CKD was defined as eGFR < 60 mL/min. We selected n = 35 articles leading to 376 169 patients, of which 76 557 CKD patients receiving BMS n = 35,807, 1st generation DES n = 37,650, or 2nd generation DES n = 3100. Patient receiving DES, compared to BMS, had a 18% lower all-cause mortality (RR 0.82, 95%CI 0.71-0.94). The composite of death or myocardial infarction (MI) was lower in DES patients (RR 0.78, 95%CI 0.67-0.91), as was stent thrombosis (ST) (RR 0.57, 95%CI 0.34-0.95), target vessel/lesion revascularization (TVR/TLR) (RR 0.69, 95%CI 0.57-0.84) and death for cardiovascular cause (RR 0.43, 95%CI 0.25-0.74). We also found a gradient between 1st and 2nd generation DES, through BMS. Second, compared to 1st generation DES, were associated with further relative risk (RR) reduction of -18% in of all-cause death, and lower incidence of stent-related clinical events: -39% RR of ST risk; -27 RR of TVR/TLR risk. Conclusions DES in CKD patients undergoing PCI were superior to BMS in reducing major adverse clinical events. This was possibly explained, by a lower risk of stent-related events as ST and TVR or TLR. Second, compared to 1st generation DES may furtherly reduce clinical events., (© 2017, Wiley Periodicals, Inc.)

Electrical storm (ES) is defined as three or more episodes of ventricular fibrillation (VF) or ventricular tachycardia (VT) within 24 h and is associated with an increased cardiac and all-cause mortality. ES is a full arrhythmic emergency, its prevalence steadily increasing along with the number of implantable cardioverter-defibrillator implanted every year in developed countries. Nowadays, little evidence exists regarding clinical predictors of ES and their potential association on mortality and heart failure (HF), nor optimal pharmacological and non-pharmacological treatment has ever been codified. The intErnationaL eLeCTRicAl storm registry (ELECTRA) is a multicentre, observational, prospective clinical study with two major aims. First, to create an international database on ES encompassing clinical features, pharmacological management, and interventional treatment strategies. Second, to describe mortality and rehospitalization rates in patients with ES over a long follow-up. The primary endpoint is all-cause mortality 3 years after the ES index event. The main secondary endpoint is hospitalization for all causes 3 years after the ES index event. Other secondary endpoints includes ES recurrences, unclustered VTs/VFs recurrences, and hospitalizations for HF worsening. A minimum of 500 patients will be included in the registry, and all patients will be followed-up for a minimum of three years. The present paper describes the background and current rationale of the ELECTRA study and details the study design, from enrolment strategy to data collection methods to planned data analysis. A brief overview of the expected results and their potential clinical and research implications will also be presented (NCT02882139).

The management of noninfarct-related arteries in patients with ST-elevation myocardial infarction (STEMI) and multivessel coronary disease (MVD) is still debated. We evaluated the prognostic impact of staged complete revascularization with percutaneous coronary intervention (PCI) in STEMI patients with MVD admitted to our hospital from 2005 to 2013. Patients undergoing staged complete revascularization (n = 300) were compared with 1:1 propensity score-matched patients with culprit lesion-only treatment (n = 300). We considered a composite primary end point of all-cause death, myocardial infarction, and urgent PCI. Secondary end points included components of the primary, cardiovascular death, any PCI excluding staged PCI. We also performed an analysis including only patients surviving at least 5 days. The median follow-up was 553 days. The primary end point occurred in 10.3% of patients in the staged complete revascularization group and in 16.3% of patients in the culprit lesion-only group (hazard ratio 0.61, 95% CI 0.38 to 0.95, p = 0.031). Although this difference was no longer significant when considering only the survivors at day 5, all-cause and cardiovascular mortalities were still reduced in the staged complete revascularization group. Complete revascularization was associated with a better outcome (hazard ratio 0.35, 95% CI 0.17 to 0.63, p = 0.005) if performed within 30 days of STEMI. In conclusion, compared with culprit lesion-only revascularization, in STEMI patients with MVD undergoing primary PCI, an approach of staged complete revascularization was associated with a better outcome., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Primary percutaneous coronary intervention (pPCI) is the treatment of choice in patients with ST-elevation myocardial infarction (STEMI) if performed by an experienced team within 120 min of first medical contact. The door to balloon time (DTB) has become a performance measure and is the focus of local, regional and national quality improvement initiatives. The primary objective of the present study was to evaluate whether the implementation of reperfusion strategies could result in shorter DTB times., Methods: In 2007, at the cath lab of the IRCCS Policlinico San Matteo (a hub of a network including 7 spoke centers), 245 pPCI were performed with a median DTB time of 116 (25th-75th percentile, 96-155) min, and <90 min only in 20% of cases. To improve time to reperfusion, the following strategies were adopted in 2010 and 2011: direct access to the cath lab without initial coronary care unit admission; activation of the cath lab based on pre-hospital ECG; a faster triage with ECG performed within 10 min and use of a dedicated ambulance for patients presenting directly to the emergency room (ER) of the hub., Results: Overall, 226 and 258 pPCI were performed in 2010 and 2011, respectively, with no differences in type of hospital admission (emergency medical service, ER, or spoke) compared with 2007. A significant DTB reduction was observed (2007 vs 2010 vs 2011: 116 [96-155] vs 99 [77-129] vs 97 [80-125] min, p<0.0001), with a significant improvement in the number of patients treated within 90 min (20 vs 41 vs 40%, p<0.0001) as a result of a significant reduction in the time from first medical contact to cath lab (86 [64-124] vs 66 [50-93] vs 62 [46-93] min, p<0.0001). By analyzing only data from 2010 and 2011, median DTB was 88 (73-104) min for patients arriving through the emergency medical service, 139 (116-179) min for patients presenting to spoke centers, and 96 (75-126) min for patients presenting to the ER, with pPCI performed within 90 min in 55%, 8% e 42% of cases, respectively. The longer DTB time of the spoke centers was solely due to transportation to the hub (emergency medical service vs spoke: 56 [42-68] vs 106 [86-147] min, p<0.0001), with no differences in time to reperfusion once the cath lab was reached., Conclusions: Based on our strategies and experience including 729 STEMI patients treated with pPCI in 2007, 2010 and 2011, a significant improvement in DTB time was achieved. The main factor affecting our results is transportation to the cath lab for patients with direct access to spoke centers. Further exploration and advocacy for DTB implementation in these patients are warranted.

Background: Mortality and morbidity after acute myocardial infarction (AMI) remain high even when myocardial reperfusion is successful. Erythropoietin (EPO) protects against experimental MI., Methods: The aim of this single-centre study was to investigate the effects of short-term high-dose erythropoietin on peripheral blood cells (PBCs) and infarct size in 30 patients with a first uncomplicated AMI undergoing percutaneous coronary intervention (PCI) who were randomly assigned to treatment with EPO (33 × 10(3)IU before PCI, and 24 and 48 h after admission), or placebo. We considered short-term CD34+ cell mobilisation, quantitative PBC gene expression in the apoptotic, angiogenic and inflammatory pathways, and enzymatically estimated infarct size. Echocardiographic and cardiac magnetic resonance studies were performed in the acute phase and six months later., Results: CD34+ cell mobilisation 72 h after admission was greater in the EPO-treated patient group (93 cells/μl [36-217] vs 22 cells/μl [6-51]; p = 0.002), who also showed higher expression of the anti-apoptotic AKT and NFkB, the pro-angiogenic VEGFR-2, and the EPO-R genes, and lower expression of the pro-apoptotic CASP3 and TP53 and pro-inflammatory IL12a genes. Moreover, they showed smaller infarct size (30% reduction in CK-MB release; p = 0.025), and a favourable pattern of left ventricular remodelling., Conclusions: Short-term high-dose EPO administration in patients with AMI treated by PCI and standard anti-platelet therapy increases the levels of circulating CD34+ cells, shifts PBC gene expression towards anti-apoptotic, pro-angiogenic and anti-inflammatory pathways, and decreases infarct size. The clinical relevance of these results needs to be confirmed in specifically tailored trials., (Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.)

Aims: We studied plasma erythropoietin (EPO) levels and their relation with CD34(+)VEGFR-2(+) (mature and progenitor endothelial cells) and CD34(+) CD133(+)VEGFR-2(+), or CD34(+) CD117(+)VEGFR-2(+) (early/immature endothelial progenitors) cells in patients with acute myocardial infarction (AMI)., Methods and Results: Fifty AMI patients undergoing percutaneous coronary intervention (PCI) within 6 h of symptom onset were enrolled. EPO, measured by ELISA, and cell subsets, by cytofluorimetric analysis, were evaluated before PCI, 24 h and 7 days afterwards. Forty-five healthy subjects (CTRLs) were studied. Plasma EPO levels were higher in AMI patients at admission, 24 h, and 7 days (P = 0.04, P = 0.0001, P = 0.001, respectively) than in CTRLs. No correlation was evidenced between EPO and haemoglobin (Hb) or haematocrit at admission or 24 h after AMI. Differently, both Hb and haematocrit inversely correlated with EPO at day 7 (P = 0.0016, P = 0.029, respectively). Plasma EPO levels correlated with CD34(+)CD133(+)VEGFR-2(+) cells at day 7 (P = 0.03)., Conclusion: AMI patients have increased plasma EPO levels until day 7. In the early phase, plasma EPO levels are Hb-independent; at day 7, an Hb-modulated increase of EPO correlates with the percentage of CD34(+)CD133(+)VEGFR-2(+) cells.