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Abstract Background This study was undertaken to compare the in vitro effects of 17β-estradiol on human epicardial coronary arteries, resistance coronary arteries and on arterial vessels usually employed as grafts in surgical myocardial revascularization. Methods Coronary artery rings (descending coronary artery, right coronary artery, circumflex coronary artery, first septal branch) and arterial graft rings (internal thoracic artery, gastro-epiploic artery) obtained from human heart donors with heart not suitable to cardiac transplantation were connected to force transducer for isometric force recording. Precontracted specimens with and without endothelium were exposed to increasing concentration of 17β-estradiol (3–30–300–3000 nmol/l) and to vehicle (0.1% v/v ethanol). We also evaluated the effects of 17β-estradiol on vessels before and 20 minutes after exposure to L-monomethyl-arginine and indomethacin. Results 17β-estradiol induced a significant relaxation in all precontracted vessels (mean maximum effect: 78,6% ± 8,5). This effect was not different among the different rings and was not related to the presence of endothelium. N-monomethyl-L-arginine and indomethacin did not modify 17β-estradiol relaxant effect. Conclusion The vasodilator action of the 17β-estradiol is similar on coronary arteries, resistance coronary arteries and arterial vessels usually employed as grafts in myocardial revascularization.

Background: Hybrid-convergent radiofrequency (RF) ablation targeting pulmonary veins (PVs) and left atrial posterior wall (LAPW) has shown better arrhythmic outcomes than an endocardial-only RF strategy, despite higher rates of complications. Comparisons with extensive pulsed field ablation (PFA) are currently lacking., Objectives: This study aimed to compare the efficacy and safety of the hybrid-convergent RF vs PFA of PVs and LAPW in long-standing persistent atrial fibrillation (LSPAF)., Methods: Ninety-three consecutive LSPAF patients, treated with 2-step hybrid-convergent RF ablation (hybrid group, n = 49) or with PFA of PVs and LAPW (PFA group, n = 44) were enrolled. Primary efficacy endpoint was defined as any atrial tachyarrhythmias (ATA) recurrence after the 3-month blanking period, over a follow-up time of 12 months. Periprocedural adverse events and late complications during follow-up were deemed primary safety outcomes., Results: The hybrid and PFA groups had similar baseline characteristics; mean age was hybrid 63.8 ± 10.6 years vs PFA 66.0 ± 7.4 years; P = 0.105. PV and LAPW ablation were acutely successful in all patients. Step 1 hybrid-epicardial procedures were longer than PFA (166 [Q1-Q3: 140-205] minutes vs 107.5 [Q1-Q3: 82.5-12] minutes; P < 0.01). At 12-month follow-up, there was no difference in ATA recurrences between groups (hybrid 36.7% vs PFA 40.9%; P = 0.680; log-rank at survival analysis P = 0.539). After adjusting for confounders, a larger left atrial volume and recurrences during the blanking-period were predictors of ATA recurrences after ablation, regardless of procedural technique employed. PFA showed a better safety profile with a lower rate of major periprocedural complications compared with hybrid ablation (12% vs 0%; P = 0.028)., Conclusions: Hybrid-convergent and PFA share comparable arrhythmic outcomes in LSPAF, but hybrid-convergent ablation carries higher periprocedural risks., Competing Interests: Funding Support and Author Disclosures Dr Tondo serves a member of scientific advisory boards for Medtronic Inc and Boston Scientific; and receives lecture/proctoring fees from Abbott Medical, AtriCure, Boston Scientific, and Medtronic Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Patients with coronary heart disease (CHD) are at very high risk of recurrent events. A strategy to reduce excess risk might be to deliver structured secondary prevention programmes, but their efficacy has been mostly evaluated in the short term and in experimental settings. This is a retrospective case-control study aimed at assessing, in the real world, the efficacy of a secondary prevention programme in reducing long-term coronary event recurrences after coronary artery bypass surgery (CABG)., Methods and Results: Programme participants (henceforth 'cases') were men and women aged <75 years subjected to CABG between 2002 and 2014, living within 100 km of the hospital. Key programme actions included optimization of treatments according to the most updated European preventive guidelines, surveillance of therapy adherence, and customized lifestyle counselling. Controls were analogous patients not involved in the programme because living farther than 100 km away, matched 1:1 with cases for gender, age at CABG, and year of CABG. Both groups (n = 1248) underwent usual periodic cardiology follow-up at our centre. Data on symptomatic or silent CHD recurrences were obtained from the hospital electronic health records. Cox analysis (adjusted for baseline differences between groups) shows that programme participation was associated with a significantly lower incidence throughout 5 years post-CABG of symptomatic [hazard ratio (95% confidence interval): 0.59 (0.38-0.94)] and silent [0.53 (0.31-0.89)] coronary recurrences., Conclusion: In a real-world setting, taking part in a structured longstanding secondary prevention programme, in addition to usual cardiology care, meaningfully lowers the risk of coronary recurrences., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: The Ozaki procedure is an innovative surgical technique aiming at the reconstruction of the aortic valve with autologous pericardium to overcome the limitations of commercially available prostheses., Methods: We retrospectively analyzed 71 patients who underwent the Ozaki operation at our center between October 2014 and February 2020., Results: No in-hospital death occurred. Freedom from major adverse valve-related events was 97%. The aortic gradients and transvalvular velocity were significantly lower at the 3-month echocardiographic control than at the predischarge echocardiography (10.93 ± 5.38, P < .01 vs 16.24 ± 7.67, P < .01, respectively). The median follow-up period was 20.7 months (range, 2 to 47). Four patients showed mild/moderate aortic insufficiency (5.6%), and none showed severe aortic valve insufficiency. No patients underwent reoperation., Conclusions: Midterm outcome follow-up of the Ozaki procedure showed optimal results in terms of mortality, transaortic valve gradients, freedom from major adverse valve-related events, and recurrence of aortic valve insufficiency., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Epidemiological data on fatal anaphylaxis are underestimated worldwide. Few Italian data do exist. The aims of the study are to determine the anaphylaxis mortality rate in Italy and its associations with demographic characteristics (gender, age, and geographical distribution), and to investigate which are the most common triggers of fatal anaphylaxis., Material and Methods: This is a descriptive study analyzing data reported to the National Register of Causes of Death database and managed by the Italian National Institute of Statistics for the years 2004-2016. An analytical method was developed to identify all the ICD-10 codes related to anaphylaxis deaths, which were divided into two classes: "Definite anaphylaxis deaths" and "Possible anaphylaxis deaths.", Results: From 2004 through 2016, 392 definite anaphylaxis deaths and 220 possible anaphylaxis deaths were recorded. The average mortality rate for definite anaphylaxis, from 2004 to 2016, was 0.51 per million population per year. Definite fatal anaphylaxis was mostly due to the use of medications (73.7%), followed by unspecified causes (20.7%) and hymenoptera stings (5.6%). Concerning possible anaphylaxis deaths, the most common cause was venom-stinging insect (51.4%). We did not find any data on food fatal anaphylaxis. Unspecified anaphylaxis accounted for 21%-28% of all cases, underlining the difficulty in accurately ascertaining the causes of fatal anaphylaxis and therefore in assigning the proper ICD-10 code., Conclusion: This is the first study of anaphylaxis-related mortality coming from an official database of the whole Italian population. However, the actual number of deaths by anaphylaxis, and their related triggers, is probably underreported, mostly due to limitations of the current recording system, and to a poor allergy education. Corrective actions should be undertaken for the benefit of the Health System., (© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

TNF-α inhibitors have demonstrated efficacy both as monotherapy and in combination with disease-modifying anti-rheumatic drugs (DMARDs) in the treatment of chronic inflammatory immune-mediated diseases such as rheumatoid arthritis, Crohn's disease, ulcerative colitis, ankylosing spondylitis (AS), psoriasis (Ps) and/or psoriatic arthritis (PsA) and may be administered off-label to treat disseminated granuloma annulare, systemic lupus erythematosus and systemic sclerosis. There are several TNF-α inhibitors available for clinical use including infliximab, adalimumab, golimumab, certolizumab pegol and etanercept. In this article, we discuss the efficacy and safety of etanercept in the treatment of spondyloarthritis and juvenile idiopathic arthritis (JIA). Etanercept is effective in the treatment of PsA, AS, JIA and uveitis. Independent predictors of achieving a sustained clinical improvement or MDA in children with JIA include shorter disease duration, no concurrent oral corticosteroid use, history of chronic anterior uveitis and age <9 years. IBD incidence was lower in patients receiving etanercept plus MTX. Intra-articular administration of etanercept seems to favor a prompt target joint improvement without serious adverse events. Etanercept improve endothelial function reducing the risk of acute cardiovascular and/or cerebrovascular events. The most commonly reported adverse events were nasopharyngitis, epidermal and dermal conditions, upper respiratory tract infection, cough, headache and fatigue.

Introduction: TNF-α inhibitors have demonstrated efficacy both as monotherapy and in combination with disease-modifying anti-rheumatic drugs (DMARDs) in the treatment of chronic inflammatory immune-mediated diseases. Etanercept is a decoy receptor" for TNF-α and it is composed of two p75 TNF-α receptors fused to human IgG1. Areas covered: We discuss the potential role of pharmacogenetics in predicting the response to etanercept in patients with Ps and PsA. Expert opinion: Pharmacogenetics represents the new frontier for the discovery of potential genetic markers of biological response to TNF-α inhibitors. Clinical studies showed that TNF-α -308 G/G, +489 GG and the +489 GA, TNF-α -857C (rs1799724), TNFRSF1B 676T (rs1061622), TNFAIP3 G SNP (rs610604), FcγRIIIA-V158F, HLA-C*06, IL-17 A (rs2275913 and rs10484879), IL-17F (rs763780) and IL17RA (rs4819554) SNPs favor the response to etanercept. However, most of these studies are often small and not sufficiently powered to detect an effect and markers tend to be more prognostic than predictive of therapeutic response. Furthermore, studies often examines only the effects of a single SNP, while it would be more useful to analyze more haplotypes in contemporary in the same patients. Appropriately designed clinical trials are needed before a pharmacogenetic approach may be applicable in daily clinical therapeutic practice.

Swan-Ganz catheter entrapment in the heart, vena cava, or pulmonary artery is rare but may lead to life-threatening events. We report a case of severe tricuspid regurgitation resulting from papillary muscle rupture during percutaneous removal of a Swan-Ganz catheter (SCG) caught by a surgical suture. We performed urgent tricuspid valve repair by suturing the ruptured papillary muscle. This report highlights preventive measures to avoid suture-related entrapment and raises a word of caution regarding percutaneous removal of accidentally entrapped SCGs., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Cilostazol is a selective inhibitor of phosphodiesterase-III with antiplatelet, antithrombotic and vasodilating properties. The aim of our study was to evaluate the effect of the drug on vasculopathy and Raynaud's phenomenon (RP), in a series of patients with systemic sclerosis (SSc), before and after cilostazol treatment. Twenty-one consecutive SSc patients with moderate or severe RP were enrolled in an open-label study. Cilostazol was administered at the dose of 100 mg twice a day, for 12 months. Evaluations included: daily RP attack diary documenting the frequency and duration of RP episodes, Health Assessment Questionnaire-Disability Index, scleroderma visual analogue scales (VAS), flow-mediated dilation and immunological status, including endothelin 1 and interleukin 6 plasma levels. Thirteen patients completed the study. RP duration and daily number episodes recorded over a 3-week period significantly decreased after cilostazol treatment (p = 0.0049 and p = 0.0067, respectively). VAS score indicated a significant amelioration of the patients' perception of RP (p = 0.0117), and both baseline and post-ischemic brachial artery diameters were significantly increased after cilostazol treatment, as compared with basal values (p = 0.0119 and p = 0.0076, respectively). None of the patients developed digital ulcers during the study. A significant clinical improvement of RP was recorded in SSc patients undergoing cilostazol treatment. Study results indicate a potential role of cilostazol as oral maintenance therapy in SSc patients with RP.

Saphenous vein (SV) graft disease represents an unresolved problem in coronary artery bypass grafting (CABG). After CABG, a progressive remodelling of the SV wall occurs, possibly leading to occlusion of the lumen, a process termed 'intima hyperplasia' (IH). The investigation of cellular and molecular aspects of IH progression is a primary end-point toward the generation of occlusion-free vessels that may be used as 'life-long' grafts. While animal transplantation models have clarified some of the remodelling factors, the pathology of human SV is far from being understood. This is also due to the lack of devices able to reproduce the altered mechanical load encountered by the SV after CABG. This article describes the design of a novel ex vivo vein culture system (EVCS) capable of replicating the altered pressure pattern experienced by SV after CABG, and reports the results of a preliminary biomechanical conditioning experimental campaign on SV segments. The EVCS applied a CAGB-like pressure (80-120 mmHg) or a venous-like perfusion (3 ml/min, 5 mmHg) conditioning to the SVs, keeping the segments viable in a sterile environment during 7 day culture experiments. After CABG-like pressure conditioning, SVs exhibited a decay of the wall thickness, an enlargement of the luminal perimeter, a rearrangement of the muscle fibres and partial denudation of the endothelium. Considering these preliminary results, the EVCS is a suitable system to study the mechanical attributes of SV graft disease, and its use, combined with a well-designed biological protocol, may be of help in elucidating the cellular and molecular mechanisms involved in SV graft disease., (Copyright © 2013 John Wiley & Sons, Ltd.)

Introduction: TNF-α inhibitors have demonstrated efficacy both as monotherapy and in combination with disease-modifying antirheumatic drugs (DMARDs) in the treatment of chronic inflammatory immune-mediated diseases such as rheumatoid arthritis, Crohn's disease, ankylosing spondylitis, psoriasis and/or psoriatic arthritis, and may be administered off-label to treat disseminated granuloma annulare systemic lupus erythematosus and systemic sclerosis. There are several TNF-α inhibitors available for clinical use including infliximab, adalimumab, golimumab, certolizumab pegol and etanercept., Areas Covered: infliximab and adalimumab can induce the development of anti-infliximab (anti-IFX) and anti-adalimumab (anti-ADA) monoclonal antibodies (mAbs). In this review, we discuss the impact of anti-IFX and anti-ADA mAbs upon efficacy and safety of these biological agents., Expert Opinion: IgG/IgE neutralizing antibodies against infliximab and adalimumab decrease the possibility of achieving a minimal disease activity state or clinical remission, decrease drug survival, increase the need for doctors to prescribe a higher drug dosage and, finally, favor the occurrence of adverse events. Concomitant administration of DMARDs such as methotrexate or leflunomide prevents the development of neutralizing Abs against infliximab and adalimumab.

Introduction: TNF-α is a pro-inflammatory cytokine known to a have a key role in the pathogenesis of chronic immune-mediated diseases. TNF-α inhibitors can be administered either as monotherapy or in combination with other anti-inflammatory or disease-modifying anti-rheumatic drugs (DMARDs) to treat chronic immune-mediated diseases., Areas Covered: Patients receiving TNF-α inhibitors are at high risk of infections. Based on our experience, in this paper, we discuss the risk of infections associated with the administration of TNF-α inhibitors and the strategies for mitigating against the development of these serious adverse events., Expert Opinion: Infliximab more so than etanercept appears to be responsible for the increased risk of infections. Re-activation of latent tuberculosis (LTB) infection and the overall risk of opportunistic infections should be considered before beginning TNF-α inhibitor therapy. A careful medical history, Mantoux test and chest-x-ray should always be performed before prescribing TNF-α inhibitors. Particular attention should be paid to risk factors for Pneumocystis jirovecii infection. Hepatitis B and C virological follow-up should be considered during TNF-α inhibitor treatment. Finally, patients who are at high risk of herpes zoster (HZ) reactivation would benefit from a second vaccination in adulthood when receiving TNF-α inhibitors.

Saphenous vein graft disease is a timely problem in coronary artery bypass grafting. Indeed, after exposure of the vein to arterial blood flow, a progressive modification in the wall begins, due to proliferation of smooth muscle cells in the intima. As a consequence, the graft progressively occludes and this leads to recurrent ischemia. In the present study we employed a novel ex vivo culture system to assess the biological effects of arterial-like pressure on the human saphenous vein structure and physiology, and to compare the results to those achieved in the presence of a constant low pressure and flow mimicking the physiologic vein perfusion. While under both conditions we found an activation of Matrix Metallo-Proteases 2/9 and of microRNAs-21/146a/221, a specific effect of the arterial-like pressure was observed. This consisted in a marked geometrical remodeling, in the suppression of Tissue Inhibitor of Metallo-Protease-1, in the enhanced expression of TGF-β1 and BMP-2 mRNAs and, finally, in the upregulation of microRNAs-138/200b/200c. In addition, the veins exposed to arterial-like pressure showed an increase in the density of the adventitial vasa vasorum and of cells co-expressing NG2, CD44 and SM22α markers in the adventitia. Cells with nuclear expression of Sox-10, a transcription factor characterizing multipotent vascular stem cells, were finally found in adventitial vessels. Our findings suggest, for the first time, a role of arterial-like wall strain in the activation of pro-pathologic pathways resulting in adventitial vessels growth, activation of vasa vasorum cells, and upregulation of specific gene products associated to vascular remodeling and inflammation.

Background: Reduction ascending aortoplasty is an alternative procedure to the replacement of the ascending aorta in case of ascending aorta aneurysm without aortic root involvement. This study was designed to evaluate the midterm follow-up of aortoplasty and to determine predictors of redilatation., Methods: From January 1, 1998, to April 30, 2005, 68 patients with dilatation of the ascending aorta underwent unsupported reduction aortoplasty in combination with other cardiac procedures. All patients underwent associated surgical procedures. Sixty patients (88.2%) underwent associated aortic valve replacement. Cumulative follow-up time was 191.4 patient-years and was 100% complete. Median follow-up time was 2.5 years, and mean follow-up time was 2.9 +/- 1.7 years (range, 0.4 to 6.3 years)., Results: The overall perioperative mortality rate was 1.5%. Overall survival estimates at 3 and 6 years were 93.3% +/- 4.5% and 89.3% +/- 5.9%, respectively. The actuarial freedom from cardiac-related death at 3 and 6 years was 100% and 95.7% +/- 4.3%, respectively. Ascending aorta redilatation occurred in 5 patients (7.5%). The actuarial freedom from redilatation at 3 and 6 years was 97.7% +/- 2.3% and 79.8% +/- 8.4%, respectively. The actuarial freedom from reoperation at 3 and 6 years was 100% and 86.3% +/- 7.5%, respectively. Only preoperative diameter was a significant predictor of redilatation using multivariate stepwise logistic regression analysis., Conclusions: Unsupported reduction aortoplasty is a safe and effective technique with low mortality, low morbidity, and rare late complications for selected chronic aneurysm of the ascending aorta with diameter less than 55 mm.