The risk of cannabis use disorder is mediated by altered brain connectivity: A chronnectome study.

The brain mechanisms underlying the risk of cannabis use disorder (CUD) are poorly understood. Several studies have reported changes in functional connectivity (FC) in CUD, although none have focused on the study of time-varying patterns of FC. To fill this important gap of knowledge, 39 individuals at risk for CUD and 55 controls, stratified by their score on a self-screening questionnaire for cannabis-related problems (CUDIT-R), underwent resting-state functional magnetic resonance imaging. Dynamic functional connectivity (dFNC) was estimated using independent component analysis, sliding-time window correlations, cluster states and meta-state indices of global dynamics and were compared among groups. At-risk individuals stayed longer in a cluster state with higher within and reduced between network dFNC for the subcortical, sensory-motor, visual, cognitive-control and default-mode networks, relative to controls. More globally, at-risk individuals had a greater number of meta-states and transitions between them and a longer state span and total distance between meta-states in the state space. Our findings suggest that the risk of CUD is associated with an increased dynamic fluidity and dynamic range of FC. This may result in altered stability and engagement of the brain networks, which can ultimately translate into altered cortical and subcortical function conveying CUD risk. Identifying these changes in brain function can pave the way for early pharmacological and neurostimulation treatment of CUD, as much as they could facilitate the stratification of high-risk individuals.

Combining L-Arginine with vitamin C improves long-COVID symptoms: The LINCOLN Survey.

INTRODUCTION: Recent evidence suggests that oxidative stress and endothelial dysfunction play critical roles in the pathophysiology of COVID-19 and Long-COVID. We hypothesized that a supplementation combining L-Arginine (to improve endothelial function) and Vitamin C (to reduce oxidation) could have favorable effects on Long-COVID symptoms. METHODS: We designed a survey (LINCOLN: L-Arginine and Vitamin C improves Long-COVID), assessing several symptoms that have been associated with Long-COVID to be administered nationwide to COVID-19 survivors; the survey also included effort perception, measured using the Borg scale. Patients receiving the survey were divided in two groups, with a 2:1 ratio: the first group included patients that received L-Arginine + Vitamin C, whereas the second group received a multivitamin combination (alternative treatment). RESULTS: 1390 patients successfully completed the survey. Following a 30-day treatment in both groups, the survey revealed that patients in the L-Arginine + Vitamin C treatment arm had significantly lower scores compared to patients who had received the multivitamin combination. There were no other significant differences between the two groups. When examining effort perception, we observed a significantly lower value (p < 0.0001) in patients receiving L-Arginine + Vitamin C compared to the alternative-treatment arm. CONCLUSIONS: Our survey indicates that the supplementation with L-Arginine + Vitamin C has beneficial effects in Long-COVID, in terms of attenuating its typical symptoms and improving effort perception.

[Sudden cardiac death in athletes: is it always not preventable?]. / La morte cardiaca improvvisa negli atleti: è sempre non prevenibile?

Sudden cardiac death (SCD) in athletes is a rare but tragic event particularly considering that in some cases it is preventable. In young athletes with cardiovascular disease the risk of SCD is 2,5 times higher than in non-athletes. In young athletes (<35 years old), the most common causes of SCD are related to pre-existing cardiovascular disorders including hypertrophic cardiomyopathy, congenital coronary anomalies, arrhythmogenic right ventricular dysplasia, commotio cordis, some channelopathies and cardiac sarcoidosis. Actually there are two approches to pre-participation athletic screening: the American one based on anamnesis and physical examination and the European one based on anamnesis, physical examination and ECG at rest. However, some disorders responsible for SCD can't be suspected through these exams and it could be useful to implement preparticipation athletic screening.

Carotid atherosclerosis and chronic hepatitis C: a prospective study of risk associations.

UNLABELLED: There are contrasting results in studies of cardiovascular risk in patients with genotype 1 chronic hepatitis C (G1 CHC). We evaluated the prevalence of carotid atherosclerosis compared with a control population in order to assess the potential association between atherosclerosis, host and viral factors, and liver histological features. In all, 174 consecutive biopsy-proven G1 CHC patients were evaluated by anthropometric and metabolic measurements and 174 patients attending an outpatient cardiology unit were used as controls. Intima-media thickness (IMT) and carotid plaques, defined as focal thickening of >1.3 mm at the level of common carotid, were evaluated using ultrasonography. All G1 CHC biopsies were scored by one pathologist for staging and grading, and graded for steatosis. Carotid plaques were found in 73 (41.9%) G1 CHC patients compared with 40 (22.9%) control patients (P < 0.001). Similarly, G1 CHC patients had a greater IMT compared with control patients (1.04 ± 0.21 versus 0.90 ± 0.16; P < 0.001). Multivariate logistic regression analysis showed that older age (odds ratio [OR] 1.047, 95% confidence interval [CI]: 1.014-1.082, P = 0.005), and severe hepatic fibrosis (OR 2.177, 95% CI: 1.043-4.542, P = 0.03), were independently linked to the presence of carotid plaques. In patients ≤55 years, 15/67 cases with F0-F2 fibrosis (22.3%) had carotid plaques, compared with 11/21 (52.3%) with F3-F4 fibrosis (P = 0.008). By contrast, in patients >55 years the prevalence of carotid plaques was similar in those with or without severe fibrosis (25/43, 58.1% versus 22/43, 51.1%; P = 0.51). CONCLUSION: Severe hepatic fibrosis is associated with a high risk of early carotid atherosclerosis in G1 CHC patients.

An unknown cause of aortic valve stenosis: polycythemia vera.

Polycythemia vera (PV) is a chronic myeloproliferative disorder characterized by an abnormal increase in red blood cells. The involvement of the heart during the course of the illness represents a common cause of morbidity and it is linked to an increased thrombogenic risk subsequent to higher blood viscosity. In our study we evaluated by echocardiography a PV patient population. Our study enrolled 44 patients affected by PV. 17 of them were women and 27 were men. Mean patient age was 66.7. The average follow-up period was 5 years and the average duration of the illness was 5.7 years, since the time of diagnosis. All patients were evaluated quarterly by a cardiovascular objective examination and an ultrasound of the heart, with regard to platelet count and hematocrit (Ht) variations during the follow-up period, according to the therapy administered. Patients were treated with hydrossiurea and pipobroman and they underwent an eritrocitoapheresis in emergency conditions in which Ht levels rose too much, in spite of the myelosuppressive therapy. The echocardiographic assessment of the heart structure and function by the B mode technique revealed the presence of a sclerocalcific degeneration of the aortic valve in 58% of patients, involving the aortic root more then the valve. An average trans-aortic flow velocity of 1.92 m/s was detected by Doppler technique; a stenosis was demonstrated in 11 patients (25.5% of the entire population). After diagnosing the presence of a stenosis, we researched a possible cause of it. PV is a systemic disease well-known causing coronary thrombosis in a more or less high percentage of patients according to the record of cases taken into account. In our experience, more then thrombotic disease, found only in 13.4% of patients, we detected a high prevalence and incidence of mild to severe aortic stenosis, found in 25.5% of the sample studied. About all possible causes of stenosis, nowadays this results dependent of Ht values at moment of diagnosis, in the light of these results, it is reasonable to infer that aortic valve stenosis could depend by high haemodynamic stress on valve that is characteristic of polycythemic patients without chemotherapy.

Role of bisoprolol in patients with long QT syndrome.

BACKGROUND: Long QT syndrome (LQTS) is a disorder of ventricular repolarization usually treated with ß-blockers, mostly with propanolol and nadolol. The aim of our study was to evaluate the role of bisoprolol in LQTS patients. METHODS: A total of 34 patients were evaluated in an average follow-up time of 93 months: 31 months without treatment, 31 months in treatment with nadolol or propanolol and 31 months in treatment with bisoprolol. The average age of patients at diagnosis was 17.3 years. The enrolled patients were followed through a semiannual electrocardiogram and an annual 24-hour Holter monitoring. All patients underwent genotyping, routine hematologic tests, and an echocardiogram. RESULTS: In 93 months there were 2 major and 12 minor cardiovascular events. Both the major events occurred in absence of ß-blocking therapy. Of the 12 minor cardiovascular events 3 occurred in absence of treatment, 7 during treatment with nadolol or propranolol, and 2 during treatment with bisoprolol. The mean heart rate at 24 h Holter was 87 bpm without treatment, 71 bpm in patients treated with propanolol and nadolol, and 70 bpm in patients treated with bisoprolol. There were not statistically significant differences between the three groups in the mean QTc. CONCLUSIONS: Beta-blocking therapy is the cornerstone of LQTS therapy but actually there is no clear indication about which beta-blocker should be used. In our experience bisoprolol proved to be less harmful and easier to manage than propranolol and nadolol in patients with LQTS, with the same effectiveness in preventing major cardiovascular events.

[Morpho-volumetric assessment of the right ventricle: a comparison between three-dimensional echocardiography and cardiac magnetic resonance]. / Valutazione morfo-funzionale del ventricolo destro: confronto tra ecocardiografia e risonanza magnetica cardiaca.

The morpho-volumetric assessment of the right ventricle (RV) is useful in the diagnosis and prognosis of many congenital and acquired cardiovascular diseases. The complexity of the right ventricular shape does not allow an adequate and satisfactory evaluation of the RV. Two-dimensional (2D) echocardiography is the most used tool for the assessment of RV function, as it is a noninvasive, reproducible and widespread technique, but the geometric assumptions required for measurement of RV volumes reduce its accuracy. At present, cardiac magnetic resonance is the gold standard for the evaluation of RV volumes because it does not need any assumption and is reproducible, though not always available. This imaging tool allows to follow-up patients and to monitor drug therapy. On the other hand, three-dimensional (3D) echocardiography overcomes several limitations of 2D echocardiography, in that it provides an estimation of RV volumes obtained through a real 3D data set, obtaining sections which cannot be technically achieved with 2D echocardiography. It is therefore useful to compare data on RV volumes and function obtained with 3D echocardiography versus cardiac magnetic resonance, mainly considering the lower costs and higher portability and availability of echocardiography.

[Diagnosis, prognosis and treatment of "myocardial bridging": state of the art and unresolved issues]. / Diagnosi, prognosi e terapia del "ponte intramiocardico": stato dell'arte e questioni irrisolte.

The current gold standard for the diagnosis of myocardial bridging is conventional coronary angiography; however, it shows only indirect signs of the disease, due to the systolic compression of the artery caused by the myocardial bridge with narrowing of the lumen and diastolic relaxation. On the other hand, computed tomography coronary angiography, even though exposing to radiation, clearly demonstrates the intramural course, the overlying muscular bands and the surrounding tissues also in asymptomatic patients and in absence of systolic compression. The prognosis of patients with myocardial bridge is usually good, but further studies are needed to evaluate the long-term prognosis of these patients, the adequate diagnostic and preventive approach and to better discern which patients should be candidate to medical, percutaneous or surgical treatment.

Airway Obstruction in Primary Care Patients: Need for Implementing Spirometry Use.

(1) Background: To detect early airway obstruction in an adult primary care setting. (2) Methods: Seventeen general practitioners (GP) were involved. A total of 912 patients consulting their GPs over 40 years were recruited: 583 of them (323M) agreed to perform/undergo all the procedures: respiratory questionnaire, mMRC questionnaire, and spirometry. We identified four subgroups: physician COPD patients; physician asthma patients; asthma-COPD overlap syndrome patients; and no respiratory diagnosis subjects, on the basis of physician diagnosis. For screening purposes, an FEV1/FVC < 70% was considered a marker of airway obstruction (AO). (3) Results: Prevalence rates of COPD, A, and ACOS were 12.5%, 7.8%, and 3.6%, respectively. In the overall sample 16.3% showed airway obstruction: 26% mild, 56% moderate, 17% severe, and 1% very severe. In obstructed subjects, those reporting neither respiratory symptoms nor a physician's respiratory diagnosis were 60% level I; 43% level II; 44% level III; and none level IV. Wheezing (p < 0.001), sputum (p = 0.01), older age (p < 0.0001), and male gender (p = 0.002) were the best predictors of airway obstruction. (4) Conclusions: A high prevalence of AO was found. In AO we found a high prevalence of subjects without respiratory symptoms or respiratory chronic diagnosis. Airway obstruction was predicted by the presence of wheezing, sputum, older age, and male gender.

Relationship between Multimorbidity and Quality of Life in a Primary Care Setting: The Mediating Role of Dyspnea.

Multimorbidity is known to impair Quality of Life (QoL) in patients in a primary setting. Poor QoL is associated with higher dyspnea perception. How multimorbidity and dyspnea perception are related to QoL needs clarification. The aim of the present study is to evaluate the mediating role of dyspnea perception in the relationship between multimorbidity and QoL in adults with and without airflow obstruction in a primary care setting. Seventeen general practitioners participated in the study: a total of 912 adult patients attending the practitioner's surgery for a generic consultation completed a preliminary respiratory screening; 566 of them answered a respiratory questionnaire between January and June 2014, and 259 of the latter (148 M, aged 40-88) agreed to go through all the of procedures including spirometry, the IMCA and QoL (SF-36 through Physical Health "PCS" and Mental Health components) questionnaires, evaluation of comorbidities and the mMRC Dyspnea Scale. For screening purpose, a cut-off of FEV1/FVC < 70% was considered a marker of airflow obstruction (AO). Of the sample, 25% showed airflow obstruction (AO). No significant difference in mMRC score regarding the number of comorbidities and the PCS was found between subjects with and without AO. Multimorbidity and PCS were inversely related in subjects with (p < 0.001) and without AO (p < 0.001); mMRC and PCS were inversely related in subjects with (p = 0.001) and without AO (p < 0.001). A mediation analysis showed that the relation between number of comorbidities and PCS was totally mediated by mMRC in subjects with AO and partially in subjects without AO. We conclude that the effect of multimorbidity on PCS is totally mediated by mMRC only in AO. Detecting and monitoring mMRC in a primary care setting may be a useful indicator for evaluating a patient's global health.

Lung Function Decline in Adult Asthmatics-A 10-Year Follow-Up Retrospective and Prospective Study.

Asthma may have an impact on lung function decline but conflicting results are reported in forced expiratory volume in one second (FEV1) decline. We aimed to describe the changes in FEV1 in lifelong non-smoking adult asthmatic outpatients during a 10-year follow-up comparing years 1-5 (1st period) with years 6-10 (2nd period) to assess factors affecting these changes. A total of 100 outpatients performed spirometry every 3 months during a 10-year survey. FEV1/Ht3 slope values of the 2nd period reduced significantly respect to the 1st period (p < 0.0001). FEV1 slopes of years 1-5 and 6-10 were inversely associated with FEV1 at enrolment (p = 0.02, p = 0.01, respectively). Reversibility and variability FEV1 showed a significant effect on the 1st period slopes (p = 0.01 and p < 0.04, respectively). Frequent exacerbators in the 1st year had steeper FEV1/Ht3 slopes in the 1st period (p = 0.01). The number of subjects using higher doses of ICS was significantly lower at the 10th years respect to the 5th and the 1st year (p < 0.001, p = 0.003, respectively). This study shows that FEV1 decline in treated adult asthmatics non-smokers, over 10-year follow-up, is not constant. In particular, it slows down over time, and is influenced by FEV1 at enrolment, reversibility, variability FEV1 and exacerbation score in the 1st year.

[Periprocedural edoxaban interruption is associated with low bleeding and thromboembolic risk: the Italian data of the EMIT-AF/VTE study]. / Sospensione perioperatoria di edoxaban associata a basso rischio di emorragia e tromboembolia: i dati italiani dello studio EMIT-AF/VTE.

BACKGROUND: So far, the only available data for edoxaban periprocedural management come from the ENGAGE AF-TIMI 48 trial. The recently published EMIT-AF/VTE study showed low periprocedural bleeding and thromboembolic risks of edoxaban in a real-world setting in patients undergoing any diagnostic or therapeutic procedures. The aim of this study was to compare descriptively Italian and European data with regard to patient characteristics and outcomes in the EMIT-AF/VTE study. METHODS: A total of 1155 patients treated with edoxaban for stroke prevention in non-valvular atrial fibrillation and with venous thromboembolism, and undergoing a wide range of diagnostic and therapeutic procedures were enrolled in 326 centers across Europe. Of these patients, 246 were from 43 Italian centers. The periprocedural interruption of edoxaban was at the physician's discretion. All the procedures were classified into minor, low, and high bleeding procedural risk according to the European Heart Rhythm Association (EHRA) definition. The primary outcome was the incidence of major bleeding. Secondary outcomes included thromboembolic events. RESULTS: Patients were older in Italy in comparison with the rest of Europe with a mean age of 74.2 vs 71.3 years. Also, the rate of comorbidities was higher in Italy (e.g. diagnosed cancer and vascular disease) than in Europe. In Italy, there was a higher rate of high bleeding risk procedures than in other European countries (37.8% vs 20.6%) and a more homogeneous distribution of all types of procedures (while in Europe 44.1% were vascular access and transcatheter diagnostic procedures and interventions). In Italy, a higher proportion of patients did not interrupt edoxaban (32.9% vs 29% in Europe). The number of major bleeding events (2 in Italy, 3 in Europe) as well as of thromboembolic events (4 in Italy, 3 in Europe) was overall low. CONCLUSIONS: In the EMIT-AF/VTE study, the number of bleeding and thromboembolic events in patients treated with edoxaban undergoing elective or unplanned procedures was low either in Italy or in the rest of Europe. The safety and efficacy of edoxaban was confirmed in Italy even if patients were older, presented more frequently with cancer, and there was a higher rate of high bleeding risk procedures by EHRA definition.

Asymptomatic carotid lesions add to cardiovascular risk prediction.

AIM: To show that subclinical atherosclerosis (subclinical-ATS) of carotid arteries [intima-media thickness (IMT) or asymptomatic carotid plaque (ACP)], may provide additional information for risk stratification, in asymptomatic patients, aged greater than 45 years, with a cluster of risk factors (RFs). METHODS AND RESULTS: We studied 558 asymptomatic patients (235 males). RFs for atherosclerosis were assessed and the 10-year-risk was calculated according to the Italian risk score. Doppler ultrasound of carotid arteries identified the presence of IMT greater than 0.9 mm in 183 patients and ACP in 147 patients. One hundred and fifty-three patients developed cerebrovascular or cardiovascular (CV) events in the follow-up: 67 developed acute myocardial infarction, 39 developed angina, 25 had a stroke or transient ischemic attack, six died for CV events, and 16 underwent percutaneous or surgical revascularization. The incidence reflected the different risk profiles (4, 14, and 20%, respectively). However, in patients with baseline subclinical-ATS the incidence of events increased to 35, 46, and 63%, respectively. In the multivariate analysis the incidence of events was significantly influenced by the presence of asymptomatic carotid lesions in each risk category. CONCLUSION: In our experience, the incidence of CV events is enhanced in patients with subclinical-ATS. Increased IMT and ACP predict CV events and improve the risk stratification of asymptomatic patients aged greater than 45 years and with a cluster of RFs, in a long-term follow-up.

The PFO anatomy evaluation as possible tool to stratify the associated risks and the benefits arising from the closure.

AIMS: According to the current guidelines, the patent foramen ovale (PFO) is still considered a qualitative factor and, as a consequence, its closure is recommended just on the basis of its 'presence'. METHODS AND RESULTS: In the year 2008, we evaluated 25 patients (mean age 62.7) with acute cerebrovascular event and 92 patients (mean age 27.3) suffering from migraine with aura. No PFO was reported in 79 patients. A venous-to-arterial circulation shunt had been shown in 38 patients (29 subjects with migraine and 9 subjects with prior stroke). According to the number of microbubbles arrived during the Valsava manoeuvre, we found: 25 small PFO, 6 moderate PFO, and 6 severe PFO. In the baseline population with migraine (n = 92), 32% (n = 29) had a PFO. A 'large' foramen was reported in approximately 9% of the migraine subjects. In the population with prior stroke (n=25), 9 patients (36%) had a PFO. A 'large' foramen was reported in 45% of the patients with ischaemic stroke. We found embryonic recesses in 13% (n = 4) of the patients with migraine and PFO (n=29) vs. 66% (n=6) of the patients with ischaemic stroke and PFO (P= 0.01). CONCLUSION: It is possible to suppose that not all PFO have the same prognostic value. The evaluation of two anatomical characteristics can allow to identify those foramina at higher risk and, as a consequence, the patients who could have a major benefit from the closure.

Heart rate turbulence for guiding electric therapy in patients with cardiac failure.

BACKGROUND: It is well-known that a reduction of the cardiac frequency variability, measurable with the Heart Rate Variability (HRV) system, is an indirect expression of the sympathetic-autonomic tone. Another index, Heart Rate Turbulence (HRT), has been recently suggested as a possible unit of measurement for the sympathetic-autonomic tone: this system allows to estimate the baro-reflex response of the carotid arteries to an early ventricular extra-systole by analysing heart rate variations induced by a premature beat. METHODS AND RESULTS: In our research we have analyzed this phenomenon in patients affected by moderate or severe cardiac failure. In particular, we divided 110 patients into two arms: subjects with or without a history of resuscitated arrhythmic death, that is, patients with high or low arrhythmic potential. In a detailed analysis of the sympathetic-autonomic tone, using both the above-mentioned parameters, HRV showed an irrelevant statistical difference between the two arms; on the contrary, HRT showed a significant statistical difference. CONCLUSIONS: If our conclusions will be confirmed by next larger reports, HRT could become a reliable index for screening the arrhythmic potential of patients affected by cardiac failure, to select the ones who need a defibrillator implantation.

Tako-tsubo cardiomyopathy and microcirculation.

BACKGROUND: Takotsubo cardiomyopathy was described for the first time in Japan in the 1990s. It is very similar to the ischemic cardiopathy both for clinical and instrumental characteristics. His peculiarity is an alteration of the ventricular contraction mechanism with hypo-akinesis of the apex and lateral segments of the left ventricle, associated with hyper-kinesis of the heart base which is responsible for the typical echocardiographic aspect of a cruet during the systole. However, the etiology of this cardiomyopathy is still unknown despite the fact that numerous hypothesis have been made. A single study of 16 patients proved multivasal damage by a BLASH SCORE analysis of the coronary radiography. In our study, performed on 24 patients, we intended to assess the actual implication of the microcirculation by analyzing the TIMI frame count (TFC), so as reporting correlations between alterations of each single artery and its respective myocardial area. METHODS AND RESULTS: Six Cardiology Centres performed an International multi-centre collection of a consecutive series of 24 patients, of which 20 were women and four men. The average age was 67.4 years. All patients admitted to one of the Cardiology divisions were previously listed for symptoms and signs of Takotsubo cardiomyopathy. An electrocardiographic (ECG), echocardio-gram and a hemodynamic study were carried out on each patient. The patients were evaluated with a follow up lasting 7 weeks. On the coronary radiography film, the microcirculation was examined by an analysis of the TFC according to the Gibson technique. The value obtained was considered pathological if it was >30 frames. The evaluation of the microcirculation by the TFC analysis showed that in 23 of the 24 patients there was a pathological slow down of the flow in the coronary micro- circulation. By analysing the number of involved vessels it was noted that nine patients had a slowdown of the general flow in all three vessels, six patients in only two vessels and the remaining nine in one vessel. In particular: in 14 patients there was an abnormal TFC in left anterior descending coronary artery (LAD), 16 in the right coronary artery (RCA) and 18 in the left circumflex coronary artery (LCX), while in one patient the picture quality in the acute phase did not allow an evaluation of the score in the RCA and in another patient in the LDA. None of the explored vessels that was responsible for the disorder of the microcirculation showed any stenosis. CONCLUSION: From the data evaluated by us, microcirculatory dysfunction seems to be present very often during acute phases of Takotsubo illness, but it is not the only determining factor of the illness.

The role of the renin-angiotensin system in atrial fibrillation and the therapeutic effects of ACE-Is and ARBS.

Atrial fibrillation (AF) is the most common rhythm disturbance in medical practice and represents a very expensive health problem. AF can be managed with the prevention of thromboembolism and either a rate control of rhythm strategy. As both strategies have important limitations, probably a preventative strategy in patients at risk of developing arrhythmia can be a more attractive option. The renin-angiotensin system (RAS) seems to be involved in the genesis of arrhythmia by the following two mechanisms: 1. the induction of atrial fibrosis and structural remodelling by mitogen-activated protein kinase (MAPK) expression and reduction of collagenase activity; 2. the induction of electrical remodelling by shortening of the atrial effective refractory period (AERP) and of the action potential duration. For these reasons it has been hypothesized that angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin-II receptor blockers (ARBs) may play a role in preventing AF recurrence. The aim of the present review was to analyse evidence supporting the usefulness of RAS inhibition in patients with AF in order to focus on which specific subset of patients it would most favour. After reviewing the literature, we conclude that, although many studies and meta-analysis have supported the advantage of RAS block in preventing AF recurrence, it is premature to recommend the use of ACE-Is and ARBs specifically for the prevention of AF. However we believe that as these drugs are safe and manageable, they should be considered the drugs of choice in patients with AF and coexisting clinical conditions such as hypertension, coronary disease, heart failure and diabetes mellitus.

Paroxysmal reciprocating supraventricular tachycardia in infants: electrophysiologically guided medical treatment and long-term evolution of the re-entry circuit.

AIMS: The aim of this study is to evaluate the long-term prognosis in infants affected by paroxysmal reciprocating supraventricular tachycardia (SVT), to identify predictors of SVT disappearance, and to assess the efficacy of electrophysiologically guided drug therapy in preventing recurrences. METHODS AND RESULTS: A six step regimen of oral therapy was used in 55 infants with SVT: (i) propafenone (P); (ii) flecainide (F); (iii) flecainide plus propranolol (FP); (iv) amiodarone (A); (v) amiodarone plus propranolol (AP); (vi) amiodarone plus flecainide plus propranolol (AFP). If one step was not successful, the patient was passed on to the next treatment step and so on. Transesophageal atrial pacing (TAP) was used to evaluate treatment efficacy and the evolution of SVT at the end of the first, second, and third year. Propafenone was successful in 32.7% of the patients, F in 14.5%, FP in 23.6%, A alone in 5.4%, and AP in 18.1%; only 7.2% reached step 6. At month 12, after therapy wash out, SVT recurred spontaneously in 2 patients (3.6%) and remained inducible in 25 (45.5%). Inducibility was significantly higher in patients treated with A. At 24 months, SVT was inducible or spontaneous in 86% of the cases and at 36 months in 87%. There were no recurrences using the treatment confirmed by TAP. No further predictor of SVT inducibility was identified. CONCLUSION: Supraventricular tachycardia disappeared in approximately 50% of the patients during the first year of life and in another 20% thereafter. The necessity for A treatment is the only predictor of persistence of the re-entry circuit during the first year of life. Transesophageal atrial pacing is useful in guiding the medical treatment.

Safety of Edoxaban 30 mg in Elderly Patients with Severe Renal Impairment.

BACKGROUND AND OBJECTIVE: Patients with atrial fibrillation (AF) and advanced chronic kidney disease (CKD) are at high risk of adverse events and are complicated to manage. There is little evidence on the effects of non-vitamin K oral anticoagulants in patients with severe CKD. Preliminary data in patients taking edoxaban whose creatinine clearance fell below 30 mL/min showed a low risk of stroke and major bleeding. The aim of our study is to test the safety of edoxaban 30 mg/day in patients with severe renal impairment with an estimated glomerular filtration rate (eGFR) of 15-29 mL/min. METHODS: We analyzed retrospective data from 46 patients who had documented AF with severe renal impairment (eGFR between 15 and 29 mL/min). The follow-up, characterized by clinical examination and blood analysis, was performed at 3, 6, and 12 months. The main endpoint was the incidence of major bleedings or clinically relevant non-major (CRNM) bleedings or thromboembolic events. RESULTS: At the time of the data collection, the average follow-up was 9.13 ± 3.0 months. There were no major bleedings, strokes, systemic embolisms, or cardiovascular deaths reported: one non-cardiac death and five minor hemorrhages occurred. No differences related to the severity of CKD were observed in the left ventricular ejection fraction at echocardiography and in the thrombotic and hemorrhagic risk profile. CONCLUSION: In this explorative study analyzing patients with severe CKD treated with edoxaban 30 mg once daily, no major bleeding or thrombotic events were observed. Some minor bleedings were observed. While additional studies are necessary to confirm the results of this exploratory study, edoxaban 30 mg once daily appears to be safe in patients with severe CKD.