Contrast-enhanced ultrasound in differentiating malignant from benign portal vein thrombosis in hepatocellular carcinoma

Portal vein thrombosis(PVT) may occur in liver cirrhosis patients. Malignant PVT is a common complication in cirrhotic patients with concomitant hepatocellular carcinoma(HCC) and, in some cases, it may be even the initial sign of an undetected HCC. Detection of malignant PVT in a patient with liver cirrhosis heavily affects the therapeutic strategy. Gray-scale ultrasound(US) is widely unreliable for differentiating benign and malignant thrombi. Although effective for this differential diagnosis, fine-needle biopsy remains an invasive technique. Sensitivity of color-doppler US in detection of malignant thrombi is highly dependent on the size of the thrombus. Contrast-enhanced computed tomography(CT) and contrast-enhanced magnetic resonance(MRI) can be useful to assess the nature of portal thrombus, while limited data are currently available about the role of positron emission tomography(PET) and PET-CT. In contrast with CT, MRI, PET, and PET-CT, contrast-enhanced ultrasound(CEUS) is a fast, effective, well tolerated and cheap technique, that can be performed even in the same session in which the thrombus has been detected. CEUS can be performed bedside and can be available also in transplanted patients. Moreover, CT and MRI only yield a snapshot analysis during contrast diffusion, while CEUS allows for a continuous real-time imaging of the microcirculation that lasts several minutes, so that the whole arterial phase and the late parenchymal phase of the contrast diffusion can be analyzed continuously by real-time US scanning. Continuous real-time monitoring of contrast diffusion entails an easy detection of thrombus maximum enhancement. Moreover, continuous quantitative analyses of enhancement(wash in- wash out studies) by CEUS during contrast diffusion is nowadays available in most CEUS machines, thus giving a more sophisticated and accurate evaluation of the contrast distribution and an increased confidence in diagnosis in difficult cases. In conclusion, CEUS is avery reliable technique with a high intrinsic sensitivity for portal vein patency assessment. More expensive and sophisticated techniques(i.e., CT, MRI, PET, and PET-CT) should only be indicated in undetermined cases at CEUS.

Electrical storm: A clinical and electrophysiological overview

Electrical storm(ES) is a clinical condition characterized by three or more ventricular arrhythmia episodes leading to appropriate implantable cardioverterdefibrillator(ICD) therapies in a 24 h period. Mostly, arrhythmias responsible of ES are multiple morphologies of monomorphic ventricular tachycardia(VT), but polymorphic VT and ventricular fibrillation can also result in ES. Clinical presentation is very dramatic in most cases, strictly related to the cardiac disease that may worsen electrical and hemodynamic decompensation. Therefore ES management is challenging in the majority of cases and a high mortality is the rule both in the acute and in the long-term phases. Different underlying cardiomyopathies provide significant clues into the mechanism of ES, which can arise in the setting of structural arrhythmogenic cardiomyopathies or rarely in patients with inherited arrhythmic syndrome, impacting on pharmacological treatment, on ICD programming, and on the opportunity to apply strategies of catheter ablation. This latter has become a pivotal form of treatment due to its high efficacy in modifying the arrhythmogenic substrate and in achieving rhythm stability, aiming at reducing recurrences of ventricular arrhythmia and at improving overall survival. In this review, the most relevant epidemiological and clinical aspects of ES, with regard to the acute and long-term follow-up implications, were evaluated, focusing on these novel therapeutic strategies of treatment.

Vitamin D and acute myocardial infarction

Vitamin D deficiency is a prevalent condition,cutting across all ethnicities and among all age groups,and occurring in about 30%-50% of the population. Besides vitamin D established role in calcium homeostasis,its deficiency is emerging as a new risk factor for coronary artery disease. Notably,clinical investigations have suggested that there is an association between hypovitaminosis D and acute myocardial infarction(AMI). Not only has it been linked to incident AMI,but also to increased morbidity and mortality in this clinical setting. Moreover,vitamin D deficiency seems to predispose to recurrent adverse cardiovascular events,as it is associated with post-infarction complications and cardiac remodeling in patients with AMI. Several mechanisms underlying the association between vitamin D and AMI risk can be involved. Despite these observational and mechanistic data,interventional trials with supplementation of vitamin D are controversial. In this review,we will discuss the evidence on the association between vitamin D deficiency and AMI,in terms of prevalence and prognostic impact,and the possible mechanisms mediating it. Further research in this direction is warranted and it is likely to open up new avenues for reducing the risk of AMI.

Chronic kidney disease in acute coronary syndromes

Chronic kidney disease(CKD) is associated with a high burden of coronary artery disease. In patients with acute coronary syndromes(ACS), CKD is highly prevalent and associated with poor short- and long-term outcomes. Management of patients with CKD presenting with ACS is more complex than in the general population because of the lack of well-designed randomized trials assessing therapeutic strategies in such patients. The almost uniform exclusion of patients with CKD from randomized studies evaluating new targeted therapies for ACS, coupled with concerns about further deterioration of renal function and therapy-related toxic effects, may explain the less frequent use of proven medical therapies in this subgroup of high-risk patients. However, these patients potentially have much to gain from conventional revascularization strategies used in the general population. The objective of this review is to summarize the current evidence regarding the epidemiology and the clinical and prognostic relevance of CKD in ACS patients, in particular with respect to unresolved issues and uncertainties regarding recommended medical therapies and coronary revascularization strategies.

Percutaneous electrochemotherapy in the treatment of portal vein tumor thrombosis at hepatic hilum in patients with hepatocellular carcinoma in cirrhosis: A feasibility study

AIMTo treated with electrochemotherapy (ECT) a prospective case series of patients with liver cirrhosis and Vp3-Vp4- portal vein tumor thrombus (PVTT) from hepatocellular carcinoma (HCC), in order to evaluate the feasibility, safety and efficacy of this new non thermal ablative technique in those patients.METHODSSix patients (5 males and 1 female), aged 61-85 years (mean age, 70 years), four in Child-Pugh A and two in Child-Pugh B class, entered our study series. All patients were studied with three-phase computed tomography (CT), contrast enhanced ultrasound (CEUS) and ultrasound-guided percutaneous biopsy of the thrombus before ECT. All patients underwent ECT treatment (Cliniporator Vitae®, IGEA SpA, Carpi, Modena, Italy) of Vp3-Vp4 PVTT in a single session. At the end of the procedure a post-treatment biopsy of the thrombus was performed. Scheduled follow-up in all patients entailed: CEUS within 24 h after treatment; triphasic contrast-enhanced CT and CEUS at 3 mo after treatment and every six months thereafter.RESULTSPost-treatment CEUS showed complete absence of enhancement of the treated thrombus in all cases. Post-treatment biopsy showed apoptosis and necrosis of tumor cells in all cases. The follow-up ranged from 9 to 20 mo (median, 14 mo). In 2 patients, the follow-up CT and CEUS demonstrated complete patency of the treated portal vein. Other 3 patients showed a persistent avascular non-tumoral shrinked thrombus at CEUS and CT during follow-up. No local recurrence was observed at follow-up CT and CEUS in 5/6 patients. One patient was lost to follow-up because of death from gastrointestinal hemorrage 5 wk after ECT.CONCLUSIONIn patients with cirrhosis, ECT seems effective and safe for curative treatment of Vp3-Vp4 PVTT from HCC.

经右侧肱动脉途径支架置入术治疗左侧颈内动脉狭窄以及牛型主动脉弓

弓上各动脉出发的复杂解剖结构或先天变异会使经股动脉入路的颈动脉支架置入（CAS）手术更加困难，并易出现并发症。本研究评价了CT用于证实左侧颈内动脉狭窄合并牛型主动脉弓的病人，经右侧肱动脉途径CAS手术的可行性、安全性和有效性。

Aortic stenosis： insights on pathogenesis and clinical implications

Aortic stenosis （AS） is a common valvular heart disease in the Western populations, with an estimated overall prevalence of 3% in adults over 75 years. To understand its patho-biological processes represents a priority. In elderly patients, AS usually involves trileaflet valves and is referred to as degenerative calcific processes. Scientific evidence suggests the involvement of an active ＂atherosclerosis-like＂ pathogenesis in the initiation phase of degenerative AS. To the contrary, the progression could be driven by different forces （such as mechanical stress, genetic factors and interaction between inflammation and calcification）. The improved understanding presents potentially new therapeutic targets for preventing and inhibiting the development and progression of the disease. Furthermore, in clinical practice the management of AS patients implies the evaluation of generalized atherosclerotic manifestations （i.e., in the coronary and carotid arteries） even for prognostic reasons. In counselling elderly patients, the risk stratification should address individual frailty beyond the generic risk scores. In these regard, the co-morbidities, and in particular those linked to the global atherosclerotic burden, should be carefully investigated in order to define the risk/benefit ratio for invasive treatment strategies. We present a detailed overview of insights in pathogenesis of AS with possible practical implications.

Cardiovascular magnetic resonance of cardiac tumors and masses

Cardiac masses diagnosis and treatment are a true challenge,although they are infrequently encountered in clinical practice.They encompass a broad set of lesions that include neoplastic(primary and secondary),non-neoplastic masses and pseudomasses.The clinical presentation of cardiac tumors is highly variable and depends on several factors such as size,location,relation with other structures and mobility.The presumptive diagnosis is made based on a preliminary non-invasive diagnostic work-up due to technical difficulties and risks associated with biopsy,which is still the diagnostic gold standard.The findings should always be interpreted in the clinical context to avoid misdiagnosis,particularly in specific conditions(e.g.,infective endocarditis or thrombi).The modern multi-modality imaging techniques has a key role not only for the initial assessment and differential diagnosis but also for management and surveillance of the cardiac masses.Cardiovascular magnetic resonance(CMR)allows an optimal non-invasive localization of the lesion,providing multiplanar information on its relation to surrounding structures.Moreover,with the additional feature of tissue characterization,CMR can be highly effective to distinguish pseudomasses from masses,as well as benign from malignant lesions,with further differential diagnosis of the latter.Although histopathological assessment is important to make a definitive diagnosis,CMR plays a key role in the diagnosis of suspected cardiac masses with a great impact on patient management.This literature review aims to provide a comprehensive overview of cardiac masses,from clinical and imaging protocol to pathological findings.

Manifold benefits of choosing a minimally fluoroscopic catheter ablation approach

We report the case of a 14-year-old boy with ventricular preexcitation. A standard, fluoroscopy guided, ablation procedure was successfully performed in a postero-midseptal region with a total fluoroscopy time of about 45 min (2430 cGy.cm2). A few hours after the procedure, preexcitation reappeared. A second ablation procedure was scheduled using the EnSite NavXTM mapping system. During mapping along the tricuspid groove, preexcitation suddenly disappeared due to mechanical "bumping" of the accessory pathway and it did not recover over the next 30 min. As per our routine practice, the phase of geometry reconstruction has been continuously recorded by the system; thus, an off-line analysis allowed to pinpoint the site of earliest activation and the site of mechanical bumping, where radiofrequency obtained the accessory pathway ablation. The second procedure was performed without using fluoroscopy at all. Thanks to the geometry reconstruction, the procedure was completely successful thus avoiding a further rehospitalization.

Difficult case of a trans-septal puncture: Use of a “SafeSept” guidewire

A 69-year-old man was admitted to our center to undergo catheter ablation of paroxysmal atrial fibrillation refractory to antiarrhythmic drug therapy. This procedure required access to the left atrium through the interatrial septum. During hospitalization, the patient performed routinely pre-procedure transthoracic echocardiography and gadolinium-enhanced cardiac magnetic resonance showing a normal anatomy of both the fossa ovalis and the interatrial septum. Access to the left atrium proved difficult and several unsuccessful attempts to perform the trans-septal puncture were made under both fluoroscopy and intracardiac echocardiography guidance, even with radiofrequency energy delivery. Finally, trans-septal puncture was successfully carried out using a novel nitinol J-shaped "Safe Sept" trans-septal guidewire, designed to cross the interatrial septum through the trans-septal needle thanks to a special sharp tip. Moreover, thanks to its rounded J shape that reduces the risk of atrial perforation, the "Safe Sept" guidewire, when advanced into the left atrium, becomes atraumatic.

Collateral findings during computed tomography scan for atrial fibrillation ablation:Let's take a look around

The growing number of atrial fibrillation catheter ablation procedures warranted the development of advanced cardiac mapping techniques, such as image integration between electroanatomical map and cardiac computed tomography. While scanning the chest before catheter ablation, it is frequent to detect cardiac and extracardiac collateral findings. Most collateral findings are promptly recognized as benign and do not require further attention. However, sometimes clinically relevant collateral findings are detected, which often warrant extra diagnostic examinations or even invasive procedure, and sometimes need to be followed-up over time. Even though reporting and further investigating collateral findings has not shown a clear survival benefit, almost all the working groups providing data on collateral findings reported some collateral findings eventually coming out to be malignancies, sometimes at an early stage. Therefore, there is currently no clear agreement about the right strategy to be followed.

Large eustachian valve fostering paradoxical thromboembolism:passive bystander or serial partner in crime?

Catheter-based closure of patent foramen ovale(PFO)is more effective than medical therapy in the prevention of recurrent stroke[1].It is likely that a proportion of patients evaluated for potential transcatheter PFO closure has actually different anatomical variants particularly common in the right atrium such as eustachian valve,Chiari network,Thebesian valve and Crista Terminalis.Notably,the eustachian valve may represent an increased risk factor for left circulation thromboembolism beyond that associated with PFO size and shunting.Such patients may benefit the most from percutaneous closure procedure.

Electrical storm in systemic sclerosis: Inside the electroanatomic substrate

We report the case of a 63-year-old woman affected by a severe form of systemic scleroderma with pul-monary involvement(interstitial fibrosis diagnosed by biopsy and moderate pulmonary hypertension) and cardiac involvement(paroxysmal atrial fibrillation, right atrial flutter treated by catheter ablation, ventricular tachyarrhythmias, previous dual chamber implantable cardioverter defibrillator implant). Because of recurrent electrical storms refractory to iv antiarrhythmic drugs the patient was referred to our institution to undergo catheter ablation. During electrophysiological proce-dure a 3D shell of cardiac anatomy was created with intracardiac echocardiography pointing out a significant right ventricular dilatation with a complex aneurysmal lesion characterized by thin walls and irregular multiple trabeculae. A substrate-guided strategy of catheter ab-lation was accomplished leading to a complete electri-cal isolation of the aneurism and to the abolishment of all abnormal electrical activities. The use of advanced strategies of imaging together with electroanatomical mapping added important information to the complex arrhythmogenic substrate and improved efficacy and safety.

Partial closure with a self-made fenestrated device of secundum atrial septal defect with severe pulmonary artery hypertension in adults

Secundum atrial septal defect(ASD)repres-ents one of the most common congenital heart diseases,accounting for up to 10%of all congenital heart defects.It is often diagnosed in adulthood due to the absence of clinical symptoms.[1]By the age of 40 years,90%of untreated patients have symptoms of exertional dyspnea,fatigue,pal-pitation,sustained arrhythmia,or even evidence of heart failure.

Feasibility of en bloc thulium laser enucleation of the prostate in a large case series. Are results enhanced by experience?

Objective:To provide the first large single-operator case series of patients who undergo“en bloc”thulium laser enucleation of the prostate(ThuLEP)and to demonstrate an improvement in enucleation efficacy with experience.Methods:We prospectively evaluated a cohort of patients with symptomatic benign prostatic hyperplasia(BPH)who underwent“en bloc”ThuLEP between May 2015 and November 2017.Association between dependent variables(delivered energy and operating time)and independent variables(adenoma volume and experience)were estimated with regression analysis.The experience was calculated as the time interval between the date of the first operation of the series and the date of the operation being considered.Results:A total of 100 patients were registered for the study.Median operative time was 56.5 min(interquartile range[IQR]:40-85 min).Median enucleation time was 17.4 min(IQR:15-21.5 min).Median enucleation index(enucleation time per adenoma gram)was 0.3 min/g(0.2-0.3 min/g).The overall operative time is not influenced by experience,but we registered a significant trend towards a reduction in the total amount of energy delivered energy normalized per adenoma gram(p=0.0148).Conclusion:We believe that further attention is needed for these new“en bloc”prostatic enucleation techniques,which can facilitate some surgical steps,leading to a widespread use of laser technology for BPH surgical treatment.

Study of the Impact of the Patient Rhythm during Cryoballoon Ablation on the Acute Biophysical Parameters

Background: Pulmonary vein isolation by means of cryoballoon is a well-established way of treatment of atrial fibrillation. The aim of the study was to compare the acute cryoballoon biophysical parameters attained during energy applications to the individual pulmonary vein during sinus rhythm versus atrial fibrillation. Methods: 100 Patients who underwent their first-time PVI using second-generation cryoballoon for symptomatic and drug-refractory AF, between the beginning of March to end of August 2016, were initially screened. 61 patients with paroxysmal AF were included in the present study. 39 patients with persistent AF were excluded. No pre-procedural anatomical imaging was reported. Results: A total of 61 patients (male 80%, age 59.3 ± 13.4 years) were included in the present analysis. A total of 243 pulmonary veins were isolated with an average of 1.87 ± 1.14 cryo energy applications per individual vein. During cryo application, there were no significant differences between applications delivered during sinus rhythm or ongoing AF in the rate of temperature drop at 5 and 30 s, rate of warming at 5 s after freezing stop or achieved balloon nadir temperature. The same also was observed for both the balloon cooling rate and warming times. Conclusions: The present analysis shows no impact of the patient baseline rhythm at the time of energy application upon the acute balloon biophysical parameters in patients with normal sinus rhythm and those with ongoing atrial fibrillation using the second-generation cryoballoon.

螺内酯可改善慢性心力衰竭患者的肺弥散功能

Aims: To evaluate whether anti- aldosteronic treatment influences lung diffusion(DLco) in chronic heart failure(HF) patients. Spironolactone improves clinical conditions and prognosis in chronic HF and reduces connective tissue matrix turnover; DLco abnormalities in chronic HF are related to increase in fibrosis and connective tissue derangement. Methods and results: Thirty stable chronic HF patients, with reduced DLco(< 80% of predicted), were randomly assigned to active treatment(25 mg spironolactone daily) or placebo in addition to conventional anti- failure treatment. They were evaluated by quality of life questionnaire, laboratory investigations, cardiopulmonary exercise test, and pulmonary function test, which included DLco and membrane diffusing capacity(DM). The evaluation was done before treatment and 6 months after. Quality of life score and standard pulmonary function tests were not significantly affected by spironolactone, while active treatment increased DLco due to an increase of DM(DLco: 18.3± 3.9 vs. 19.9± 5.5 mL/min/mmHg; DM: 28.1± 7.7 vs. 33.3± 8.6 mL/min/mmHg) and peak oxygen consumption(peak VO2 16.8± 1.9 vs. 18.6± 2.2mL/min/kg). Increments of DLco and peak VO2 were linearly related(R=0.849, P< 0.001). Conclusion: These data showa positive effect of spironolactone on gas diffusion and exercise capacity suggesting a novel mechanism by which anti- aldosteronic drugs improve HF clinical condition and prognosis.

接受不同抗凝治疗的房颤患者于心脏复律前行经食管超声心动图的有效性

Objectives: To evaluate the prevalence of atrial thrombi in patients with atrial fibrillation undergoing different anticoagulation regimens before cardioversion; to evaluate the usefulness of transoesophageal echocardiography(TOE) guided cardioversion to prevent thromboembolic complications; and to correlate the presence of atrial thrombi with clinical and echocardiographic data. Methods: 757 consecutive patients admitted as candidates for cardioversion of atrial fibrillation were enrolled in the study. They were divided into four groups: effective conventional oral anticoagulation, short term anticoagulation, ineffective oral anticoagulation or subtherapeutic anticoagulation, and effective oral anticoagulation with a duration of< 3 weeks for various clinical reasons. All patients underwent TOE before cardioversion; in the presence of atrial thrombi or extreme left atrial echo contrast, cardioversion was postponed. The incidence of thromboembolic events was evaluated after cardioversion. Results: Atrial thrombi were detected in 48 of the 757(6.3%) patients. No significant differences in the percentage of atrial thrombosis were found in the four study groups. Patients with atrial thrombosis were older and had a higher percentage of mitral prosthetic valves, lower left ventricular ejection fraction, more severe atrial spontaneous echo contrast, and lower Doppler left atrial appendage velocities. 648 patients were scheduled for cardioversion. Cardioversion was successful in 89%of patients without any major thromboembolic event. Conclusions: The prevalence of atrial thrombosis before cardioversion despite different treatments with anticoagulants is about 7%and a TOE guided approach may prevent the risk of embolie events.

Relevance of Spike/Estrogen Receptor-αinteraction for endothelial-based coagulopathy induced by SARS-CoV-2

Dear Editor,The severe coagulation syndrome in numerous organs is the major life-threatening conditions characterizing the acute infection by SARS-CoV-2.Endothelial inflammation/dysfunction,platelet hyper-reactivity,generation of neutrophil extracellular traps,promote the activation of the coagulation cascade in an infection-dependent manner.^(1)

欧洲卒中组织脑静脉血栓形成诊断和治疗指南

背景和目的 目前的脑静脉血栓形成（cerebral venous thrombosis, CVT）诊断和治疗指南是欧洲神经病学学会联盟在2010年发布的，本文旨在通过更为通俗易懂和循证的方法对先前的指南进行更新。 方法 我们遵循推荐意见分级评估、制定和评价（Grading of Recommendations, Assessment, Development and Evaluation, GRADE）系统，提出相关诊断和治疗问题、进行系统评价并根据现有的科学证据质量制定推荐意见。 结果 我们建议通过磁共振血管造影或CT血管造影对CVT进行确诊，但不建议对CVT患者常规进行血栓形成倾向或癌症筛查。我们推荐对急性CVT进行胃肠外抗凝治疗，并进行减压手术以避免因脑疝而引起死亡。我们建议在急性期优先选用低分子肝素而非直接口服抗凝药。我们不建议使用类固醇和乙酰唑胺来降低死亡或生活依赖风险。我们建议对早期有癫痫发作以及幕上病变的患者应用抗癫痫药来预防进一步的早期癫痫发作。关于急性期后抗凝治疗的疗程、溶栓和（或）机械血栓切除术、治疗性腰椎穿刺以及利用抗癫痫药预防远期癫痫发作，我们无法提出推荐意见。我们建议既往有CVT史的女性应避免使用含有雌激素的避孕药。患CVT之后妊娠是安全的，但建议应在整个妊娠期和产褥期考虑预防性使用低分子肝素。 结论 需要多中心观察性和实验性研究来提高支持CVT诊断和治疗推荐意见的证据水平。