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Aims In the current literature, results of the low-voltage bridge (LVB) ablation strategy for the definitive treatment of atrioventricular nodal re-entry tachycardia (AVNRT) seem to be encouraging also in children. The aims of this study were (i) to prospectively evaluate the mid-term efficacy of LVB ablation in a very large cohort of children with AVNRT, and (ii) to identify electrophysiological factors associated with recurrence. Methods and results One hundred and eighty-four children (42% male, mean age 13 ± 4 years) with AVNRT underwent transcatheter cryoablation guided by voltage mapping of the Koch’s triangle. Acute procedural success was 99.2% in children showing AVNRT inducibility at the electrophysiological study. The overall recurrence rate was 2.7%. The presence of two LVBs, a longer fluoroscopy time and the presence of both typical and atypical AVNRT, were found to be significantly associated with an increased recurrence rate during mid-term follow-up. Conversely, there was no significant association between recurrences and patient’s age, type of LVB, lesion length, number of cryolesions or catheter tip size. Conclusion The LVB ablation strategy is very effective in AVNRT treatment in children. Recurrences are related to the complexity of the arrhythmogenic substrate.

Atherosclerotic cardiovascular disease is the leading cause of morbidity and mortality worldwide. Several cardiovascular risk factors are implicated in atherosclerotic plaque promotion and progression and are responsible for the clinical manifestations of coronary artery disease (CAD), ranging from chronic to acute coronary syndromes and sudden coronary death. The advent of intravascular imaging (IVI), including intravascular ultrasound, optical coherence tomography and near-infrared diffuse reflectance spectroscopy has significantly improved the comprehension of CAD pathophysiology and has strengthened the prognostic relevance of coronary plaque morphology assessment. Indeed, several atherosclerotic plaque phenotype and mechanisms of plaque destabilization have been recognized with different natural history and prognosis. Finally, IVI demonstrated benefits of secondary prevention therapies, such as lipid-lowering and anti-inflammatory agents. The purpose of this review is to shed light on the principles and properties of available IVI modalities along with their prognostic significance.

Post-ischemic left ventricular (LV) remodeling is a biologically complex process involving myocardial structure, LV shape, and function, beginning early after myocardial infarction (MI) and lasting until 1 year. Adverse remodeling is a post-MI maladaptive process that has been associated with long-term poor clinical outcomes. Cardiac Magnetic Resonance (CMR) is the best tool to define adverse remodeling because of its ability to accurately measure LV end-diastolic and end-systolic volumes and their variation over time and to characterize the underlying myocardial changes. Therefore, CMR is the gold standard method to assess in vivo myocardial infarction extension and to detect the presence of microvascular obstruction and intramyocardial hemorrhage, both associated with adverse remodeling. In recent times, new CMR quantitative biomarkers emerged as predictive of post-ischemic adverse remodeling, such as T1 mapping, myocardial strain, and 4D flow. Additionally, CMR T1 mapping imaging may depict infarcted tissue and assess diffuse myocardial fibrosis by using surrogate markers such as extracellular volume fraction, which may predict functional recovery or risk stratification of remodeling. Finally, there is emerging evidence supporting the utility of intracavitary blood flow kinetic energy and hemodynamic features assessed by the 4D flow CMR technique as early predictors of remodeling.

AIM: This study evaluates the risk factors associated with right ventricular (RV) dilation and dysfunction leading to pulmonary valve replacement (PVR) or adverse cardiac events in repaired Tetralogy of Fallot (rToF) patients.METHODS: Data from all rToF patients who underwent magnetic resonance imaging (MRI) evaluation at our hospital between February 2007 and September 2020 were collected.RESULTS: Three hundred and forty-two patients (60% males, 42% older than 18 years), with a median age of 16 years (IQR 13-24) at the time of MRI, were included. All patients underwent complete repair at a median age of 8 months (IQR 5-16), while palliation was performed in 56 patients (16%). One hundred and forty-four patients (42%) subsequently received pulmonary valve replacement (PVR). At the multivariate analysis, male gender was an independent predictor for significant RV dilation, RV and left ventricular (LV) dysfunction. Transventricular ventricular septal defect (VSD) closure and previous palliation significantly affected LV function and RV size, respectively. Male gender and the transventricular VSD closure were independent predictors for PVR.CONCLUSIONS: Male gender and surgical history (palliation, VSD closure approach) significantly affected the long-term outcomes in rToF patients and should be taken into consideration in the follow-up management and in PVR timing in this patient population.

Atrial fibrillation (AF) is one of the most common cardiovascular complications in patients hospitalized with community-acquired pneumonia (CAP). However, predisposing clinical factors associated with AF in CAP patients have not been fully elucidated. We enrolled 545 patients consecutively hospitalized for CAP. Data on demographic characteristics and co-morbidities were collected and all patients underwent ECG, echocardiography, and laboratory measurements. During the in-hospital stay, 9.5% of patients experienced a new episode of AF within 24 to 72 hours from admission. CAP patients who experienced AF had a higher indexed left atrial area (LAAi) and a higher proportion of concentric left ventricular hypertrophy than those not presenting AF. Univariate logistic regression analysis showed that hypertension, history of coronary heart disease, high Pneumonia Severity Index classes, history of paroxysmal AF, systolic heart failure, concentric left ventricular hypertrophy, and an enlarged LAAi were associated with a new episode of AF. A multivariable logistic analysis showed that history of paroxysmal AF (odds ratio [OR] 11.7; 95% confidence interval [CI] 5.8 to 23.7; p0.001), enlarged LAAi (OR 5.4; 95% CI 2.5 to 11.9; p0.001), and concentric left ventricular hypertrophy (OR 2.2; 95 CI 1.1 to 4.6; p = 0.034) remained independently associated with AF occurrence. In conclusion, in this large cohort of CAP patients, history of paroxysmal AF, enlarged LAAi, and concentric left ventricular hypertrophy are independent predictors of AF occurrence during the early stages of pneumonia.

Aims Women’s participation is steadily growing in medical schools, but they are still not sufficiently represented in cardiology, particularly in cardiology leadership positions. We present the contemporary distribution of women leaders in cardiology departments in the World Health Organization European region. Methods and results Between August and December 2020, we applied purposive sampling to collect data and analyse gender distribution of heads of cardiology department in university/third level hospitals in 23 countries: Austria, Azerbaijan, Belgium, Bosnia-Herzegovina, Croatia, France, Germany, Greece, Italy, North Macedonia, Morocco, Poland, Portugal, Russia, Serbia, Slovakia, Slovenia, Spain, Switzerland, Tunisia, Turkey, Ukraine, and the UK. Age, cardiology subspecialty, and number of scientific publications were recorded for a subgroup of cardiology leaders for whom data were available. A total of 849 cardiology departments were analysed. Women leaders were only 30% (254/849) and were younger than their men counterpart (♀ 52.2 ± 7.7 years old vs. ♂ 58.1 ± 7.6 years old, P = 0.00001). Most women leaders were non-interventional experts (♀ 82% vs. ♂ 46%, P < 0.00001) and had significantly fewer scientific publications than men {♀ 16 [interquartile range (IQR) 2–41] publications vs. ♂ 44 (IQR 9–175) publications, P < 0.00001}. Conclusion Across the World Health Organization European region, there is a significant gender disparity in cardiology leadership positions. Fostering a diverse and inclusive workplace is a priority to achieve the full potential and leverage the full talents of both women and men.

Background Brugada syndrome (BrS) is an inheritable disease with an increased risk of sudden cardiac death. Although several score systems have been proposed, the management of children with BrS has been inconsistently described. Objective The purpose of this study was to identify the characteristics, outcome, and risk factors associated with cardiovascular and arrhythmic events (AEs) in children younger than 12 years with BrS. Methods In this single-center case series, all children with spontaneous or drug/fever-induced type 1 Brugada electrocardiographic (ECG) pattern and younger than 12 years at the time of diagnosis were enrolled. Results Forty-three patients younger than 12 years at the time of diagnosis were included. The median follow-up was 3.97 years (interquartile range 2–12 years). In terms of first-degree atrioventricular block, premature beats, nonmalignant AEs, malignant AEs, and episodes of syncope, no significant differences were observed either between patients with spontaneous and drug/fever-induced type 1 Brugada ECG pattern or between female and male patients (except a significant difference between female and male patients for first-degree atrioventricular block). A higher incidence of malignant AEs was observed in patients with syncope (3 of 8 [37.5%] vs 0 of 35 [0%]; P = .005) than in patients without syncope. SCN5A mutations were associated with a higher occurrence of malignant AEs (3 of 14 [21.4%] vs 0 of 25 [0%]; P = .04) compared with no SCN5A mutations. Conclusion A spontaneous type 1 Brugada ECG pattern is not associated with a higher incidence of syncope, first-degree atrioventricular block, premature beats, nonmalignant AEs, and malignant AEs than the drug/fever-induced type 1 Brugada ECG pattern. Syncope events are correlated with an increased incidence of malignant AEs. Moreover, SCN5A mutations are associated with a higher occurrence of malignant AEs.

Duchenne muscular dystrophy (DMD) cardiomyopathy (DCM) is characterized by a hypokinetic, dilated phenotype progressively increasing with age. Regular cardiac care is crucial in DMD care. Early recognition and prophylactic use of angiotensin converting enzyme inhibitors (ACEi) are the main stay therapeutic strategy to delay incidence of DMD-DCM. Pharmacological treatment to improve symptoms and left ventricle (LV) systolic function, have been widely implemented in the past years. Because of lack of DMD specific drugs, actual indications for established DCM include current treatment for heart failure (HF). This review focuses on current HF strategies to identify, characterize, and treat DMD-DCM.

Background: The impact of genetic syndromes on cardiac magnetic resonance imaging (cMRI) parameters, particularly on right and/or left ventricular dysfunction, associated with clinical parameters following the repair of Tetralogy of Fallot (rToF) is not well known. Therefore, this study aimed to assess the differences in clinical, surgical, and cMRI data in syndromic and non-syndromic rToF patients. Methods: All syndromic rToF patients undergoing a cMRI without general anesthesia between 2010 and 2020 who were able to match with non-syndromic ones for birth date, sex, type of surgery, timing of cMRI, and BSA were selected. Demographic, clinical, surgical, MRI, ECG, and Holter ECG data were collected. Results: A total of one hundred and eight rToF patients equally subdivided into syndromic and non-syndromic, aged 18.7 ± 7.3 years, were studied. Del22q11.2 and Down syndrome (DS) were the most frequent syndromes (42.6% and 31.5%, respectively). Regarding the cMRI parameters considered, left ventricular (LV) dysfunction (LVEF < 50%) was more frequently found in syndromic patients (p = 0.040). In addition, they were older at repair (p = 0.002) but underwent earlier pulmonary valve replacement (PVR) (15.9 ± 5.6 vs. 19.5 ± 6.0 years, p = 0.049). On multivariate Cox regression analysis, adjusted for age at first repair, LV dysfunction remained significantly more associated with DS than del22q11.2 and non-syndromic patients (HR of 5.245; 95% CI 1.709–16.100, p = 0.004). There were only four episodes of non-sustained ventricular tachycardia in our cohort. Conclusions: Among the cMRI parameters commonly taken into consideration in rToF patients, LV dysfunction seemed to be the only one affected by the presence of a genetic syndrome. The percentage of patients performing PVR appears to be similar in both populations, although syndromic patients were older at repair and younger at PVR. Finally, the number of arrhythmic events in rToF patients seems to be low and unaffected by chromosomal abnormalities.

Background Alternative right ventricular (RV) sites (RVAPS) have been proposed to prevent or reduce RV pacing-induced left-ventricular (LV) dysfunction. Nonfluoroscopic 3D electroanatomic mapping systems (EAM) have been developed to guide cardiac catheter navigation and reduce fluoroscopy during electrophysiological procedures or pacemaker implantations. Aim The aim of the study was to compare the results of EAM-guided permanent pacemaker implantation aiming at RVAPS with conventional fluoroscopic-guided implantation in RV apex (RVA) in children and adolescents. Methods A prospective, randomized analysis was performed on children/adolescents with complete atrioventricular block (CAVB) who underwent EAM-guided pacemaker and transvenous leads implantation into RVAPS (EAM-RVAPS) or conventional, fluoroscopic-guided implantation into RV apex (RVA). In EAM-RVAPS, a pacing map guided the implantation of ventricular leads in septal sites with narrower QRS. After implantation, LV contractility (ejection fraction [EF], Global Longitudinal Strain [GLS]) and synchrony were evaluated at 1-12 months. Results Twenty-one pediatric patients with CAVB, with (six patients) or without structural heart diseases, aged 4-16 (median 10.5) years, were divided in two groups: EAM-RVAPS (11 patients, four dual-chamber/DDD, seven single-chamber/VVIR pacemakers) and RVA (10 patients, one DDD/nine VVIR). The two groups did not show significant differences for preoperative parameters. EAM-RVAPS showed: preserved LVEF and synchrony (not significantly different than RVA), significantly lower GLS and radiation doses/exposures, in spite more complex procedures, significantly longer procedure times and narrower paced QRS than RVA. Conclusions EAM-guided procedures have been useful to reduce radiation exposure and to localize RVAPS with narrower paced QRS and lower GLS than RVA.

End-stage dilated cardiomyopathy (DCM) is the leading cause of morbidity and mortality in patients with Duchenne Muscular Dystrophy (DMD). No studies are available on the effect of ivabradine on long-term outcomes in end-stage DMD/DCM.We prospectively enrolled a cohort of end-stage DMD/DCM patients with LV ejection fraction40%, on chronic HF treatment with an ACE inhibitor referred consecutively from 2012 to 2017 to Bambino Gesù Children's Hospital. In each patient, before starting HRR strategy and after 1 year, we collected medical records comprehensive of clinical, demographic and imaging parameters, BNP levels, neurological and respiratory assessment.Twenty male patients with DMD/DCM with a mean age of 15.0 ± 3.5 (13-19 IQR) years were enrolled and divided into 2 groups according to ivabradine therapy. This group showed a higher incidence of MACEs compared to others in treatment with ivabradine (87.5% vs 12.5%, p = 0.025). At Kaplan Meier survival analysis curves, the rate free from MACEs was higher in patients treated with ivabradine (log rank p = 0.017). At multivariate Cox regression analysis, ivabradine therapy was an independent predictor of freedom from MACEs (H.R. 0.078, 95% CI 0.007-0.877, p = 0.039).HRR strategy, whether achieved by beta blockers alone or in combination with ivabradine, seemed to be effective in reducing the incidence of acute adverse events, reaching optimal target heart rate and improving left ventricular function in DMD/DCM patients.

Adults hospitalized for community-acquired pneumonia (CAP) have an increased risk of myocardial infarction. Corticosteroid treatment lowers CAP morbidity and mortality, but it is not known whether it influences in-hospital myocardial infarction.The aim of the present study was to investigate the potential interplay between corticosteroid treatment and in-hospital myocardial infarction in adults with CAP.We retrospectively analyzed adults with CAP referred to the University Hospital Policlinico Umberto I (Rome, Italy), consecutively recruited, and prospectively followed until discharge. The primary outcome was the occurrence of myocardial infarction during hospitalization. We used propensity score-adjusted Cox models to examine the association between corticosteroid use and myocardial infarction.Seven hundred fifty-eight patients (493 males, 265 females; mean ± standard deviation age, 71.7 ± 14.4 yr) were included in the study. Of these, 241 (32%) were treated with systemic corticosteroids (methylprednisolone, betamethasone, or prednisone). During follow-up, 62 (8.2%) had a myocardial infarction during their hospitalization (incidence, 0.72 per 100 person-days; 95% confidence interval [CI], 0.55 to 0.92). Those treated with corticosteroids had a lower incidence of myocardial infarction (0.42 per 100 person-days) than those not treated with corticosteroids (0.89 per 100 person-days; absolute rate difference, -0.48 per 100 person-days; 95% CI, -0.85 to -0.10). In a propensity score-adjusted Cox model, corticosteroid use was associated with a lower incidence of myocardial infarction (hazard ratio, 0.46; 95% CI, 0.24 to 0.88; P = 0.02).We found that in-hospital corticosteroid treatment was associated with a lower incidence of myocardial infarction in adults hospitalized with CAP.

The new Advisor HD Grid Sensor Enabled mapping catheter (Abbott Medical Italia S.p.A., Agrate Brianza, Italy) has been recently used in different clinical settings. This new multipolar catheter with small electrodes and very short inter-electrode space has been proved to be effective and safe in left atrial mapping for atrial fibrillation ablation procedures,1 as well as for right ventricle premature ventricular contraction mapping2 and for left ventricle epicardial mapping.3 In the last years, different authors have described 3D voltage mapping of the Koch triangle in order to find low-voltage bridges as targets for a successful transcatheter ablation (TCA) of the slow pathway in children.4 Although this new strategy seems to be very promising, mapping can be difficult, operator-dependent, and time-consuming.

Community-acquired pneumonia (CAP) is complicated by cardiovascular events as myocardial infarction and stroke but the underlying mechanism is still unclear. We hypothesized that endothelial dysfunction may be implicated and that endotoxemia may have a role.Fifty patients with CAP and 50 controls were enrolled. At admission and at discharge, flow-mediated dilation (FMD), serum levels of endotoxins and oxidative stress, as assessed by serum levels of nitrite/nitrate (NOx) and isoprostanes, were studied.At admission, a significant difference between patients with CAP and controls was observed for FMD (2.1±0.3 vs 4.0±0.3%, p0.001), serum endotoxins (157.8±7.6 vs 33.1±4.8pg/ml), serum isoprostanes (341±14 vs 286±10 pM, p=0.009) and NOx (24.3±1.1 vs 29.7±2.2μM). Simple linear correlation analysis showed that serum endotoxins significantly correlated with Pneumonia Severity Index score (Rs=0.386, p=0.006). Compared to baseline, at discharge CAP patients showed a significant increase of FMD and NOx (from 2.1±0.3 to 4.6±0.4%, p0.001 and from 24.3±1.1 to 31.1±1.5μM, p0.001, respectively) and a significant decrease of serum endotoxins and isoprostanes (from 157.8±7.6 to 55.5±2.3pg/ml, p0.001, and from 341±14 to 312±14 pM, p0.001, respectively). Conversely, no changes for FMD, NOx, serum endotoxins and isoprostanes were observed in controls between baseline and discharge. Changes of FMD significantly correlated with changes of serum endotoxins (Rs=-0.315; p=0.001).The study provides the first evidence that CAP is characterized by impaired FMD with a mechanism potentially involving endotoxin production and oxidative stress.

Background and objective Community-acquired pneumonia (CAP) is associated with an increased risk of arterial and venous thrombosis but the underlying pathophysiological mechanisms are still unclear. We investigated if, in patients with CAP, a pro-thrombotic state does exist and its relationship with serum levels of endotoxins. Methods A total of 104 consecutive patients with CAP were prospectively recruited and followed up until discharge. At admission and at discharge, serum endotoxins, systemic markers of clotting activation and zonulin, a marker of gut permeability, were analysed. Hospitalized patients matched for gender, age and comorbidities but without infections were used as control. Results At admission, CAP patients showed higher plasma levels of F1 +2, a marker of thrombin generation (P = 0.023), and lower levels of protein C (PC; P

Community-acquired pneumonia (CAP) is often complicated by elevation of cardiac troponin, a marker of myocardial injury that can be isolated or associated with myocardial infarction (MI). A retrospective study showed that corticosteroid treatment lowers the incidence of MI during the hospital stay. No data exist so far on the effect of corticosteroids on myocardial injury in CAP patients. The primary objective of the study is to evaluate if methylprednisolone is able to reduce myocardial injury, as assessed by serum high-sensitivity cardiac T Troponin (hs-cTnT), in a cohort of patients hospitalized for CAP. Secondary aims are to evaluate the potential effect of methylprednisolone on cardiovascular events during hospitalization, at 30 days from hospital admission and during 2 years’ follow-up. The trial will also examine whether the potential protective effects of methylprednisolone might be due to platelet activation down-regulation. Double-blind randomized placebo-controlled trial. One hundred twenty-two eligible patients will be randomized to a week treatment with iv methylprednisolone (20 mg b.i.d) or placebo from hospital admission. Serum hs-cTnT will be measured at admission and every day until up 3 days from admission. ECG will be monitored every day until discharge. After discharge, all patients will be followed-up 2 years. This is the first clinical trial aimed at examining whether methylprednisolone treatment may reduce myocardial injury. The results of this trial may constitute the basis for conducting a larger multicenter trial aimed to evaluate the effect of corticosteroid on cardiovascular events in this setting.

Background: Platelet activation and oxidative stress seem to play a key role in coronary thrombus formation and are associated with thrombus burden in ST-elevation myocardial infarction (STEMI). However, the interplay between oxidative stress and platelet activation has not been fully elucidated. Materials and Methods: For 32 patients with STEMI undergoing primary percutaneous coronary intervention (PPCI) and 10 patients with stable angina (SA) and oxidative stress, as assessed by NADPH isoform 2 activity (soluble Nox2-derived peptide, sNox2-dp), levels of oxidized low-density lipoproteins (oxLDLs) and platelet activation markers such as soluble CD40 Ligand (sCD40L) and soluble P-selectin (sP-selectin) were measured in the retrieved material (coronary thrombi plus blood waste) of STEMI patients and in intracoronary blood of SA patients, respectively, and in peripheral blood samples of both groups. Results: In aspirated thrombi and blood waste of STEMI patients we found higher serum levels of sNox2-dp, oxLDLs, sCD40L, and sP-selectin, as compared to the intracoronary blood samples of SA patients. Moreover, in thrombi and blood waste of STEMI patients, a direct correlation between markers of oxidative stress and of platelet activation was found. Also, in STEMI patients a progressive increase of oxidative stress and platelet activation markers was observed according to the thrombus score burden. STEMI patients showed higher peripheral blood Nox2 activity and oxLDL levels as compared to SA patients. Conclusion: This study shows a close relationship between oxidative stress and platelet activation in the intracoronary blood waste and aspirated thrombi of STEMI patients, suggesting a role of oxidative stress in promoting thrombus formation and growth.

Background: Gut microbiota seems to be implicated in the athero-thrombotic process. Its relationship with coronary thrombosis has never been investigated. Methods: Serum levels of bacterial lipopolysaccharides (LPS) against Escherichia Coli (EC) and EC DNA amplification by polymerase chain reaction, plasma sP-selectin, a marker of platelet activation, and zonulin, a marker of gut permeability, were measured in patients with ST-elevation myocardial infarction (STEMI) (n=50) or stable coronary disease (SA) (n=50) and controls (n=50). Serum LPS and sP-selectin were also measured in coronary thrombi and coronary blood of patients with STEMI and stable coronary disease, respectively. Immuno-histochemical analysis was performed in coronary thrombi of 12 STEMI patients. Finally, in vitro study was undertaken to evaluate if LPS stimulate leucocyte-platelet interaction. Results: Compared to controls, patients with SA and STEMI had higher systemic levels of LPS (p Conclusion: Bacterial LPS is detected in coronary thrombi of STEMI patients and may be implicated in the thrombotic process via leucocyte-mediated platelet activation.

Background: Previous reports suggest that patients hospitalized for community-acquired pneumonia (CAP) have an enhanced risk of myocardial infarction (MI). Glucocorticoids have been proposed for the treatment of CAP. Although a recent meta-analysis showed that glucocorticoids can reduce morbidity and mortality in severe CAP, their role in the treatment of pneumonia remains unclear. Experiments in vitro and in vivo demonstrated that glucocorticoids inhibit platelet aggregation and platelet-related arterial thrombosis. Since enhanced platelet activation seems to play a role in the occurrence of MI in CAP patients, aim of the study was to assess the impact of glucocorticoids on MI occurrence in a cohort of patients hospitalized for CAP. Methods and Results: Consecutive patients admitted to the University-Hospital Policlinico Umberto I (Rome, Italy) with CAP were recruited and prospectively followed-up until discharge. The primary outcome of the study was the occurrence of an MI during hospitalization. Seven-hundred fifty-eight patients (493 males, 265 females; age: 71.7 ± 14.4 years) were included in the study: 241 (32%) were treated with systemic glucocorticoids (methylprednisolone, betamethasone or prednisone) during in-hospital follow-up, whereas 517 patients were not treated with systemic glucocorticoids. During the follow-up, 62 patients (8.2%) had an MI. Compared to the nonglucocorticoid group, patients treated with glucocorticoids showed a lower incidence of MI (9.5% vs. 5.4%; p=0.011). A Cox regression analysis showed that age, a history of coronary heart disease, and a major degree of respiratory impairment (pO2 Conclusion: This study shows that in-hospital glucocorticoids treatment is associated with a lower incidence of MI within hospital-stay in a large cohort of patients with pneumonia.

Atrioventricular Septal Defect (AVSD) is a rare congenital heart defect (CHD) often associated with genetic syndromes, most commonly Down syndrome (DS). Over the last four decades, surgical repair has increased survival and improved quality of life in these patients. The prevalence of bradyarrhythmias namely, atrioventricular block (AVB) and sinus node dysfunction (SND) in AVSD is partially known. 522 cases with both partial and complete AVSD (38.7% with DS), undergoing intracardiac repair from 1982 to 2016 at our institution, were reviewed from our system database. 38 (7.3%) patients received permanent PM implantation for AVB (early or late) or SND. On one hand, AVB requiring PM was found in 26 (4.98%). This was further subdivided into early-onset 14 (2.6%) and late-onset AVB 12 (2.2%) (median 4 [IQR 1-7] years). On the other hand, 12 (2.3%) experienced late SND requiring PM (median 11 [IQR 3.5-15.2] years). Early and late AVB were independent from the type of AVSD (partial or complete), whereas the late SND was remarkably observed in complete AVSD compared to partial AVSD (p = 0.017). We classified the cohort into two main categories: DS (202, 38.7%) and non-DS (320, 61.3%). At Kaplan-Meier survival analysis, DS was significantly associated with late-onset bradyarrhythmias (p = 0.024). At Cox regression analysis, we identified DS as an independent predictor of PM implantation (HR 2.17). In conclusion, about 7% of repaired AVSD patients need PM implantation during follow-up. There are no differences in early and late AVB occurrence according to the type of AVSD. There is a higher incidence of late SND in repaired complete AVSD, with a later timing onset in patients with associated DS. Moreover, DS seems to be an independent predictor of PM implantation.

AIM Young patients with operated complex congenital heart defects (CHD) often develop sinus node dysfunction (SND) requiring permanent pacing with rate-responsive function. Activity-driven sensors cannot account for nonmovement stress and cannot modulate heart rate physiologically. Closed Loop Stimulation (CLS, Biotronik, Berlin, Germany) is a physiological rate-responsive pacemaker based on the indirect measure of ventricular contractility. No data are available on the effects of such pacing strategy in young patients. METHODS We report a series of nine patients with CHD and SND who underwent single-chamber CLS-atrial pacing with endocardial or epicardial lead. During the first 30 days, the pacemaker was programmed in AAI pacing mode and then was switched to CLS-atrial pacing mode. An in-hospital control was scheduled 1-2 months later to evaluate the CLS response to neurovegetative stresses (i.e., nonmovement stress [Stroop color test, handgrip] and exercise stress test) and Holter monitor. CLS pacing was compared with rate-responsive accelerometer-driven pacing (AAIR). RESULTS At telemetric interrogation, CLS pacing showed a more physiological pattern of 24-h heart rate trends than accelerometer sensors. The data obtained during nonmovement/exercise stress demonstrated a physiological increase in the pacing rate with CLS, in synergy with spontaneous events. The accelerometer sensor histogram, during nonmovement stress, showed a "nonresponse" behavior (only lower rate events), and during exercise test showed most events in lower rate range. Holter monitoring showed increase of average and maximum heart rate compared with AAIR. CONCLUSION In young CHD patients, endocardial/epicardial CLS-atrial pacing demonstrated a physiological response of heart rate to neurovegetative and physical stresses.

Community-acquired pneumonia (CAP) may be complicated by atrial fibrillation (AF) but the underlying mechanism is still unclear. Nox2-derived oxidative stress has been suggested to favour AF.We consecutively enrolled 432 patients hospitalised for CAP. Nox2 activity, as assessed by serum levels of soluble Nox2 (sNox2-dp), was evaluated in each CAP patient. A 12-lead electrocardiography was repeated every 24 h. All patients were followed up until discharge.Forty-one patients with CAP (9.5%) experienced a new episode of AF within 24-72 h after hospital admission. Patients who experienced AF showed higher blood levels of sNox2-dp compared to those who did not (35.2±15.1 vs 27.0±12.5 pg/mL; p0.001). Pneumonia Severity Index score (p=0.014), history of paroxysmal AF (p0.001) and sNox2-dp (p=0.019) were independently associated with AF. At discharge, serum sNox2-dp levels were significantly decreased in the entire cohort (27.8±13.0 vs 21.9±6.8 pg/mL; p0.001). Twenty-three out of 41 CAP patients with AF returned to sinus rhythm (56%); patients who remained in AF showed significantly higher baseline and discharge levels of sNox2-dp compared to those without AF (p0.001) or with the 23 AF patients who returned to sinus rhythm (p0.05). In vitro study showed that platelets or leucocytes incubated with endotoxin, at concentrations similar to those found in the circulation of CAP patients, elicited Nox2 up-regulation, suggesting endotoxin as a trigger of oxidative stress.AF may be detected in the early phase of CAP and is associated with Nox2 activation, suggesting a role for oxidative stress in promoting this cardiac arrhythmia.NCT01773863.

Cardiovascular magnetic resonance (CMR) is a useful noninvasive technique for determining the presence of microvascular obstruction (MVO) and intramyocardial hemorrhage (IMH), frequently occurring in patients after reperfused myocardial infarction (MI). MVO, or the so-called no-reflow phenomenon, is associated with adverse ventricular remodeling and a poor prognosis during follow-up. Similarly, IMH is considered a severe damage after revascularization by percutaneous primary coronary intervention (PPCI) or fibrinolysis, which represents a worse prognosis. However, the pathophysiology of IMH is not fully understood and imaging modalities might help to better understand that phenomenon. While, during the past decade, several studies examined the distribution patterns of late gadolinium enhancement with different CMR sequences, the standardized CMR protocol for assessment of IMH is not yet well established. The aim of this review is to evaluate the available literature on this issue, with particular regard to CMR sequences. New techniques, such as positron emission tomography/magnetic resonance imaging (PET/MRI), could be useful tools to explore molecular mechanisms of the myocardial infarction healing process.

ummary An enhanced risk of cardiovascular mortality has been observed after pneumonia. Epidemiological studies have shown that respiratory tract infections are associated with an increased risk of thrombotic-related vascular disease such as myocardial infarction, ischemic stroke and venous thrombosis. Myocardial infarction and stroke have been detected essentially in the early phase of the disease (i.e. within 48 h from hospital admission), with an incidence ranging from as low as 1% to as high as 11%. Age, previous cardiovascular events and high pneumonia severity index were independent predictors of myocardial infarction; clinical predictors of stroke were not identified. Deep venous thrombosis and pulmonary embolism may also occur after pneumonia but incidence and clinical predictors must be defined. The biological plausibility of such an association may be deduced by experimental and clinical studies, showing that lung infection is complicated by platelet aggregation and clotting system activation, as documented by up-regulation of tissue factor and down-regulation of activated protein C. The effect of antithrombotic drugs has been examined in experimental and clinical studies but results are still inconclusive.

Cystic adrenal neoplasms are uncommon and may be incidentally discovered during radiologic procedure not directly performed for the evaluation of adrenal disease. Cystic pheochromocytomas are uncommon neoplasms that originate from the adrenal medulla, clinically differing from the more frequent solid pheochromocytomas. Here, we report a case of 72 year-old woman affected by asymptomatic pseudocystic pheochromocytoma (70x50mm), incidentally discovered, with a false negative 123I-monoiodobenzylguanidine (123I-MIBG) scintigraphy. Histopathological examination led to diagnosis of pseudocystic pheochromocytoma with typical architecture. The screening for germline mutation of succinate dehydrogenase complex subunits (SDHB, SDHC), Von Hipple-Lindau syndrome (VHL) and multiple endocrine neoplasia type 2 (RET) genes were negative, finding only some polymorphisms for RET and SDHB. We emphasize the relevance of an accurate pre-operative diagnosis, especially in rare diseases, and the requirement of experience and multidisciplinary management in these rare pathologies.

Background. Adiponectin (APN) possesses anti-inflammatory and antiatherogenic effects. Atrial fibrillation (AF) is burdened by enhanced systemic inflammation and platelet activation, as documented by increased blood levels of soluble CD40L (sCD40L). The interplay between APN and platelet activation in AF is still undefined.Materials and Methods. Circulating levels of APN and sCD40L were measured in 257 anticoagulated nonvalvular AF patients. Exclusion criteria were as follows: prosthetic heart valves, cardiac revascularization in the previous year, severe cognitive impairment, chronic infectious or autoimmune diseases, and active cancer.Results. Mean age was 72.9 (±8.7) years and 41.6% were female. Serum APN and plasmatic sCD40L were inversely correlated (R−0.626,P<0.001). A progressive increase of sCD40L across tertiles of CHA2DS2-VASc score was observed (rS 0.473,P<0.001), whilst APN was inversely correlated (rS −0.463, P<0.001). A multivariable linear regression analysis showed that CHA2DS2-VASc score (B−0.227,P<0.001) and sCD40L (B−0.524,P<0.001) correlated to APN.Conclusions. AF patients at high risk of stroke disclose low and high levels of APN and sCD40L, respectively, suggesting a role for APN if it favors platelet activation in vivo in this clinical setting. Enhancing APN levels may be a future goal to reduce the risk of vascular outcomes in AF patients.

Persistent oxidative stress may play a key role in microvascular obstruction (MVO). We aimed at assessing the role of platelet gp91phox (NOX2), the catalytic subunit of NADPH oxidase in MVO.We enrolled 40 patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention within 12 h from symptoms onset, either with angiographic MVO (n=20) or good angiographic myocardial reperfusion (MR) (n=20). Angiographic MVO was defined as a final thrombolysis in myocardial infarction (TIMI) flow ≤2 or TIMI flow of 3 with myocardial blush grade2. NOX2 and isoprostanes (8-iso-PGF2α) levels, as assessed by enzyme-linked immunoadsorbent assay (ELISA) or by an enzyme immunoassays, respectively, were measured on admission, at 24 h and pre-discharge.NOX2 levels increased from baseline to pre-discharge in patients with angiographic MVO (20.25 (15-24.75) pg/ml vs 25.50 (17-29.25) pg/ml, p=0.02), but not in MR patients (p=0.45), with a significant interaction between baseline and pre-discharge levels among the two groups (p=0.04). The levels of 8-iso-PGF2α showed a trend to increase from baseline to pre-discharge in angiographic MVO patients (295 (183.50-389.25) pmol/l vs 322 (206-370) pmol/l, p=0.06), but not in patients with MR (p=0.56), with a trend for interaction between baseline and pre-discharge levels among the two groups (p=0.09).Patients with MVO, but not those with myocardial reperfusion, have a sustained increase of NOX2 and 8-iso-PGF2α. Therapies targeting NOX2 or high dosage antioxidants should be tested for MVO prevention and treatment.

Statins are powerful lipid-lowering drugs that inhibit cholesterol biosynthesis via downregulation of hydroxymethylglutaryl coenzyme-A reductase.1 They are largely used in patients with or at risk of cardiovascular disease inasmuch as randomized trials have consistently shown that statins lower the rate of myocardial infarction, stroke, and cardiovascular death.2 The majority of trials with statins investigated patients with stable atherosclerotic disease, in whom the reduction in cardiovascular events appeared to be related to the cholesterol-lowering effect of statins and ultimately to plaque stabilization.3 However, experimental data demonstrated that statins may also exert a direct antithrombotic effect in models of arterial and venous thrombosis via a mechanism unrelated to the cholesterol-lowering activity4,5; this may suggest that statins inhibit several pathways of hemostasis, including platelet activation and coagulation cascade. Consistent with these observations are the potential negative properties that have been observed, including the association between statin therapy and cerebral hemorrhage. In this review, we present experimental data in support of the ability of statins to interfere directly with the clotting system and platelet activation, as well as the clinical settings that suggest that statins exert beneficial effects related to their antithrombotic properties. Colli et al6 were the first to show that statins interfere with activation of the clotting system and the coagulation cascade. Specifically, they demonstrated that fluvastatin dose-dependently inhibits activity of tissue factor (TF), a glycoprotein that converts factor X to factor Xa,7 and suggested that downexpression of geranylgeranylated protein is implicated in TF lowering. These data were confirmed in patients affected by polygenic hypercholesterolemia8 in whom simvastatin 20 mg/d for 8 weeks resulted in downregulation of TF antigen and activity and thrombin generation. Of note, inhibition of clotting activation, as assessed by plasma values of prothrombin fragment F1+2, a marker of …

SummaryThe effect of lipopolysaccharide (LPS) on platelet aggregation is still controversial. We performed in vitro and ex vivo studies in controls and in patients with community-acquired pneumonia (CAP) to assess the effect of LPS on platelet activation (PA). LPS (15–100 pg/ml) significantly increased PA only if combined with sub-threshold concentrations (STC) of collagen or ADP; this effect was associated with increased platelet H2O2 production, Nox2 activation, PLA2 phosphorylation, thromboxane (Tx)A2 and 8-iso-PGF2α-III, and was inhibited by aspirin, TxA2 receptor antagonist or by Toll-like receptor 4 blocking peptide (TLR4bp). Analysis of up-stream signalling potentially responsible for Nox2 and PLA2 activation demonstrated that LPS-mediated PA was associated with phosphorylation of AKT, p38 and p47phox translocation. In 10 consecutive CAP patients serum endotoxins were significantly higher compared to 10 controls (145 [115–187] vs 18 [6–21] pg/ml; pSupplementary Material to this article is available online at www.thrombosis-online.com

Community-acquired pneumonia (CAP) is associated with an increased risk of arterial and venous thrombosis but the underlying pathophysiological mechanisms are still unclear. We investigated if, in patients with CAP, a pro-thrombotic state does exist and its relationship with serum levels of endotoxins.A total of 104 consecutive patients with CAP were prospectively recruited and followed up until discharge. At admission and at discharge, serum endotoxins, systemic markers of clotting activation and zonulin, a marker of gut permeability, were analysed. Hospitalized patients matched for gender, age and comorbidities but without infections were used as control.At admission, CAP patients showed higher plasma levels of F

BACKGROUND Angiographic and electrocardiographic (ECG) indexes of microvascular obstruction (MVO) have been described. We aimed at assessing by cardiac magnetic resonance (CMR) anatomical features underlying concordance between them. METHODS Forty-one patients were enrolled. Patients presented with neither angiographic nor ECG indexes of MVO (without MVO) (44%), with either angiographic or ECG indexes of MVO (discordant with MVO) (22%) or with both angiographic and ECG indexes of MVO (concordant with MVO) (34%). All patients underwent in-hospital CMR. Echocardiographic data obtained after 6 months were compared with those obtained in hospital. RESULTS Concordant patients with MVO had larger infarct size, lower myocardial salvage index and higher rate of myocardial haemorrhage (all assessed by CMR) [33% (25-41%), 15% (10-29%) and 88%, respectively] as compared with patients without MVO [12% (9-16%), 66% (52-79%) and 0%; Bonferroni-adjusted P

The natriuretic peptides (NP) are a group of structurally related but genetically distinct peptides that exert diverse actions on cardiovascular, renal and endocrine functions. The NP system includes three principal peptides: atrial natriuretic peptide (ANP), B-type natriuretic peptide (brain natriuretic peptide, BNP) and C-type natriuretic peptide (CNP). ANP has important effects on blood pressure and cardiac function regulation by promoting natriuresis, diuresis and vasorelaxation. Previous studies have demonstrated a significant contribution of ANP into the pathophysiological basis of cardiovascular diseases, i.e. hypertension and heart failure. In fact, ANP levels are found to be elevated in hypertension as well as in heart failure, where they parallel the progression of the underlying cardiac disease. Of interest, high NT-proANP levels predict the cardiovascular risk and the mortality for cardiovascular events in the general population. More recently, the molecular genetic approach has shown a significant impact of the ANP gene and of its structural alterations on susceptibility to develop vascular damage and the consequent clinical sequelae in both an animal model and in humans. Furthermore, a pharmacogenomic study has proven the beneficial effects of a diuretic-based therapy in hypertensive carriers of 2238CC ANP variant. In this regard, ongoing studies from our group are exploring the fine mechanisms underlying vascular damage induced by human ANP gene structural alterations. A new view of ANP strongly supports its role in the susceptibility to vascular damage development, mainly dependent on either altered gene structure or abnormal plasma concentrations. Thus, a careful characterization of NT-proANP/ANP in the clinical setting is recommended since it represents a valuable tool for prognostic, diagnostic and therapeutic strategies.

In this article we address the issue of the continuing growing burden of morbidity and mortality associated to cardiovascular disease, by focusing on how this could be limited by implementing cardiovascular disease prevention strategies. In particular, we propose to: 1) performing a more comprehensive evaluation of total CV risk, especially in patients at high baseline risk profile; 2) achieving a risk reduction through a global therapeutic interventionon the different components of CV risk; 3) improving strategies aimed at global CV risk reduction in future years, especially in patients at high risk, and implementing armonization of guidelines for risk management. The burden of CV disease can be effectively reduced by adopting a more comprehensive approach to identification, risk stratification and treatment of individuals along the cardiovascular continuum.

Cushing syndrome (CS) may associate with a cardiomyopathy whose substrate is poorly understood. A total of 8 of 473 consecutive patients with dilated cardiomyopathy (DCM) (1.6%, 4 male, 4 female, mean age 61 ± 4.9 years) had CS due to adrenal adenoma. Diagnosis of CS was supported by typical

Community-acquired pneumonia (CAP) is complicated by cardiac events in the early phase of the disease. Aim of this study was to assess if these intrahospital cardiac complications may account for overall mortality and cardiovascular events occurring during a long-term follow-up. Three hundred one consecutive patients admitted to the University-Hospital, Policlinico Umberto I, with community-acquired pneumonia were prospectively recruited and followed up for a median of 17.4 months. Primary end point was the occurrence of death for any cause, and secondary end point was the occurrence of cardiovascular events (cardiovascular death, nonfatal myocardial infarction [MI], and stroke). During the intrahospital stay, 55 patients (18%) experienced a cardiac complication. Of these, 32 had an MI (29 non-ST-elevation MI and 3 ST-elevation MI) and 30 had a new episode of atrial fibrillation (7 nonmutually exclusive events). During the follow-up, 89 patients died (51% of patients with an intrahospital cardiac complication and 26% of patients without, p0.001) and 73 experienced a cardiovascular event (47% of patients with and 19% of patients without an intrahospital cardiac complication, p0.001). A Cox regression analysis showed that intrahospital cardiac complications, age, and Pneumonia Severity Index were significantly associated with overall mortality, whereas intrahospital cardiac complications, age, hypertension, and diabetes were significantly associated with cardiovascular events during the follow-up. In conclusion, this prospective study shows that intrahospital cardiac complications in the early phase of pneumonia are associated with an enhanced risk of death and cardiovascular events during long-term follow-up.