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International audience; Quasi-vertical gallium nitride (GaN) Schottky diodes on silicon carbide (SiC) substrates were fabricated for frequency multiplier applications. The epitaxial structure employed had an n− layer of 590 nm with doping 6.6 × 1016 cm−3, while the n+ layer was 950 nm thick, with doping 2 × 1019 cm−3. Potassium hydroxide (KOH) chemical surface treatment before Schottky contact metallization was employed to study its effect in improving the diode parameters. The KOH-treated diode demonstrated a breakdown voltage of − 27.5 V, which is the highest reported for this type of diode. Cut-off frequencies around 500 GHz were obtained at high reverse bias (− 25 V) in spite of high series resistance. The result obtained in breakdown voltage value warrants further research in surface treatment and post-annealing of the Schottky contact optimization in order to decrease the series resistance.

Funding Acknowledgements Type of funding sources: None. Background Cardiac Magnetic Resonance (CMR) represents the gold standard for morpho-functional assessment and for myocardial tissue characterization. Although Mapping technique provided added value to tissue characterization, data on Mapping in athletes are still scarce and differences between sport disciplines have not been evaluated. Purpose To compare T1 and T2 Mapping values between Olympic Athletes engaged in different types of sport and a control group of sedentary subjects. Methods A group of Olympic athletes with unremarkable cardiovascular pre-participation screening prior the Olympic games underwent CMR without contrast administration. A group of sedentary subjects was enrolled as a control group. Cine, native T1 and T2 Mapping were analyzed. Athletes were divided in different sports categories according to the ESC classification. Results 265 Olympic athletes (15% skill, 19% power, 25% mixed, 41% endurance - 58% male) and 21 controls were enrolled. Comparing athletes of different sport categories and sedentary controls, endurance presented the lowest value of T1 Mapping. T2 Mapping was slightly higher in endurance athletes but were within normal limits (referred to local normal range) (Table). Compared with males, female athletes had higher values of T1 native myocardial Mapping [956 (934-981) vs 941 (926-963); p=0,004], while there were no significant differences regarding T2 Mapping values (p=0,874) (Figure). Conclusion T1 was lower and T2 Mapping slightly higher athletes engaged in endurance compared to other sport disciplines and sedentary controls. Female athletes showed higher T1 native myocardial Mapping compared with males, while T2 Mapping did not show differences.

Funding Acknowledgements Type of funding sources: None. Background Intense and prolonged exercise training induces morpho-functional cardiac changes, known as "athlete’s heart". The physiologic nature of this cardiac remodeling has been questioned and data on reversibility of cardiac remodeling, especially of the right ventricle (RV), after the suspension of high intensity training are scarce. Purpose To describe cardiac morpho-functional changes by echocardiography in a group of Olympic athletes prior the Olympic games (T1) and years after cessation of their competitive athletic career (T2). Methods Endurance athletes evaluated prior their participation to the Olympic games (edition 2004-2008-2012) and after cessation of their athletic career (> 3 years of cessation of intensive exercise training) were invited to be evaluated at our Institute. 12-lead ECG, exercise ECG test and echocardiogram were performed. Echocardiogram parameters at T1 and T2 were compared including left ventricle (LV) and RV dimension, systolic and diastolic function. Results 25 athletes were enrolled (mean age 47±2 years). The mean time from the end of their agonistic activity was 12 ± 7 years. No differences in terms of LV dimensions and function were observed (Table). Veterans showed a significant decrease in RV dimensions and improvement in function at T2 compared to T1. Conclusion After suspension of competitive training, Veteran athletes showed reverse remodeling of the right ventricle compared with the evaluation during the peak training by echocardiography.

Funding Acknowledgements Type of funding sources: None. Background Several determinants affect cardiac remodelling in athletes, including sport discipline, body size and sex. Recently, interest in myocardial deformation (MD) imaging as reliable functional index is growing. Available MD data are usually derived by echocardiography and mostly related to the evaluation of the left ventricle. Data on right ventricle (RV) deformation assessed by CMR are lacking and, currently, specific reference values in athletes have not been explored. Purpose To assess RV deformation in a cohort of Olympic athletes and to evaluate possible inter-individual differences related to type of sport and sex. Methods A cohort of Olympic athletes with unremarkable cardiovascular pre-participation screening tests was enrolled. A group of sedentary individuals was also enrolled for comparison. All subjects underwent CMR without contrast. Cine-images were post-processed to assess RV volume, ejection fraction (EF) and MD by computing global longitudinal strain (GLS) by feature-tracking software. Athletes were divided in subgroups based on sex, ESC sport classification and RV enlargement (RVEDV/LVEDV>1 or ≤1). Results 265 Olympic athletes (15% skill, 19% power, 25% mixed, 41% endurance; 58% male) and 21 sedentary controls were enrolled. Endurance athletes showed the greatest RV remodeling in terms of volumes (Table). No differences in RV-EF were found comparing athletes of different sport categories, but between athletes and sedentary controls. Median value of RV-GLS of the whole athletic cohort was -23 (-21, -25). There were no significant differences among the different sport disciplines other than endurance vs. sedentary controls for RV-GLS. Female athletes showed higher values of RV-GLS when compared with males. When examined with regard to presence of RV enlargement, no differences were observed (Figure). Conclusion Endurance athletes showed the greatest right ventricle remodelling in terms of RV volumes and function. Specifically, they showed the highest values of RV volumes and the lowest values of RV-GLS of the entire athlete’s population, but still within the normal range. Female athletes had higher RV-GLS values when compared with males. No difference was observed between athletes with dilated RV compared to non-dilated RV.

Funding Acknowledgements Type of funding sources: None. Background Athletes of endurance disciplines present the highest level of cardiac remodelling often generating concerns for differential diagnosis with cardiomyopathies. In addition to standard morpho-functional evaluation, left ventricle (LV) myocardial deformation (MD) and estimated intra-ventricular hemodynamic forces (HDFs) are emerging diagnostic tools, particularly in heart failure patients. In the athletic population MD data are scarce while HDFs are lacking. Purpose To describe MD and HDFs evaluated by CMR feature-tracking in a cohort of endurance Olympic athletes and to evaluate the possible relationship with LV geometry. Methods A group of endurance Olympic athletes evaluated prior the Olympic games and with unremarkable cardiac pre-participation screening tests was enrolled. All athletes underwent CMR without contrast administration. Cine images were post-processed to evaluate end-diastolic and end-systolic LV volumes, ejection fraction (LVEF), global longitudinal and circumferential strain (GLS and GCS) and estimated HDFs by a dedicated feature-tracking software. HDFs were measured in apex-base (AB) and latero-septal (LS) directions, over the entire cardiac cycle, in systole and diastole. LS/AB ratio was also derived to determine forces distribution. Athletes were divided in subgroups according to the 3D sphericity index (< 40% or 40%). A group of sedentary subjects was enrolled as a control group. Results 109 endurance Olympic athletes (62% male; mean age 26 ± 5 years) and 21 sedentary subjects were enrolled. Athletes with increased sphericity index (≥40%) were 61 (56%) and presented with greater EDV, ESV and lower LVEF compared to those without increased sphericity and controls (Table). No significant differences were found between athletes and controls regarding LV-GLS and GCS. HDFs distribution was not different between groups and even athletes with a more spherical LV shape showed an HDFs diastolic ratio comparable to those of athletes with lower sphericity index and control. Conclusion Although more than half of endurance athletes presented with altered geometry (increased sphericity index), strain parameters and hemodynamic forces were not different from sedentary controls and those athletes without increased sphericity. The use of advanced parameters to evaluate cardiac function could be used as a tool to confirm the benign nature of cardiac adaptation due to intense exercise training.

International audience; A model to predict the ideal reverse leakage currents in Schottky barrier diodes, namely, thermionic emission and tunneling components, has been developed and tested by means of current–voltage–temperature measurements in GaN-on-SiC devices. The model addresses both current components and both forward and reverse polarities in a unified way and with the same set of parameters. The values of the main parameters (barrier height, series resistance, and ideality factor) are extracted from the fitting of the forward-bias I–V curves and then used to predict the reverse-bias behavior without any further adjustment. An excellent agreement with the I–V curves measured in the forward bias in the GaN diode under analysis has been achieved in a wide range of temperatures (275–475 K). In reverse bias, at temperatures higher than 425 K, a quasi-ideal behavior is found, but additional mechanisms (most likely trap-assisted tunneling) lead to an excess of leakage current at lower temperatures. We demonstrate the importance of the inclusion of image-charge effects in the model in order to correctly predict the values of the reverse leakage current. Relevant physical information, like the energy range at which most of the tunnel injection takes place or the distance from the interface at which tunneled electrons emerge, is also provided by the model.

Funding Acknowledgements Type of funding sources: None. Background Cardiac magnetic resonance (CMR) provides an effective contribution for the prevention of sudden cardiac death with its ability to provide accurate information on morpho-functional abnormalities and on myocardial tissue characterization. However, data on its utility in clinical scenario in the competitive athletes are limited to selected cohort of patients with complex arrhythmias. Objective To retrospectively analyze all the CMR performed at our center for evaluating the predictors of positive CMR findings in a large cohort of competitive and non-competitive athletes presenting with different clinical indications. Methods Over a period of 30 months all the CMR performed on athletes aged > 14 years and training for at least 5 hours per week at our Institutes were retrospectively recruited. The following data were also collected: medical history, ECG, echocardiography, exercise testing. CMR were categorized as "positive" or "negative" based on the presence or absence of late gadolinium enhancement (LGE, excluding RV insertion point) and/or morphological and/or functional abnormalities. Predictors of "positive" CMR were explored. Results 503 CMR were recruited and the most frequent indications for CMR were: ventricular arrythmias (n= 213, 42%), ECG abnormalities (n= 140, 28%) followed by echocardiogram abnormalities, symptoms and family history (Figure A). 308 (61%) CMR were "negative" and 195 (39%) "positive" (Figure B). Uncommon ventricular arrythmias did not result associated with positive CMR (p= 0.43), while polymorphic ventricular beats are associated with positive CMR (p= 0.02). Among ECG abnormalities only T-waves inversion, particularly on lateral and infero-lateral leads, were associated with positive CMR (p= 0.04). Conclusion Ventricular arrhythmias represented the most common indication for require a CMR but in almost half the cases, the CMR was negative. Excises induced ventricular arrhythmias is not significantly associated with pathological findings on CMR, while the polymorphic morphology of arrhythmias and the presence of lateral and infero-lateral repolarization abnormalities on ECG were associated with positive CMR.

Funding Acknowledgements Type of funding sources: None. Background Non-invasive evaluation of left ventricular hemodynamic forces (HDFs) by Cardiac Magnetic Resonance (CMR) is a promising tool to improve systolic and diastolic evaluation. No data are available on athletic population. Purpose To provide the range of normal values of HDFs in Olympic athletes and to evaluate the possible influence of different sport categories. Methods A group of Olympic athletes evaluated prior the Olympic games with unremarkable cardiovascular pre-participation screening tests underwent CMR without contrast administration. A group of sedentary subjects was enrolled as a control group. Cine-images were post-processed by a feature-tracking based software to estimate HDFs. HDFs were measured in apex-base (AB) and latero-septal (LS) directions, over the entire heartbeat, in systole and diastole. Athletes were divided in subgroups according to ESC sport classification for comparison. They were also divided according to the ejection fraction (EF ≤ or >53%). Results 93 elite athletes (33% power, 33% mixed, 33% endurance) were enrolled. HDFs in AB and LS direction were 20.5%± 4.3 and 2.9%± 0.7 in the entire heartbeat, 32.6% ± 7 and 3.6%± 1 in systole, 11%± 4.1 and 2.3%± 0.8 in diastole. Comparing athletes of different sport category and sedentary controls no significant differences were found between groups (Table). Comparing athletes with ejection fraction (EF) £ 53% and > 53%, the former showed lower values of AB-HDFs assessed in the entire heartbeat and in systole (18.9 ± 4.6 % vs 20.9 ± 4.1; p= 0.024 and 29.6 ± 6.3 vs 33.3 ± 7; p= 0.024, respectively), but within the normal range. Conclusion We provide normal range for HDFs assessed by CMR in elite athletes and no differences were observed between sedentary controls and athletes involved in different sport categories. Comparing athletes with low-normal and normal ejection fraction, the former showed lower values of AB-HDFs but within the normal range.

Background: Diagnosis of heart failure with preserved ejection fraction (HFpEF) in patients with dyspnea and paroxysmal atrial fibrillation (AF) is challenging. Speckle tracking-derived left atrial strain (LAS) provides an accurate estimate of left ventricular (LV) filling pressures and left atrial (LA) phasic function. However, data on clinical utility of LAS in patients with dyspnea and AF are scarce. Objective: To assess relationship between the LAS and the probability of HFpEF in patients with dyspnea and paroxysmal AF. Methods: The study included 205 consecutive patients (62 ± 10 years, 58% males) with dyspnea (NYHA≥II), paroxysmal AF and preserved LV ejection fraction (≥50%), who underwent speckle tracking echocardiography during sinus rhythm. Probability of HFpEF was estimated using H2FPEF and HFA-PEFF scores, which combine clinical characteristics, echocardiographic parameters and natriuretic peptides. Results: Patients with high probability of HFpEF were significantly older, had higher body mass index, NT-proBNP, E/e’, pulmonary artery pressure and larger LA volume index than patients in low-to-intermediate probability groups (all p < 0.05). All components of LAS and LA strain rate showed proportional impairment with increasing probability of HFpEF (all p < 0.05). Out of the speckle tracking-derived parameters, reservoir LAS showed the largest area under the curve (AUC = 0.78, p < 0.001) and the strongest independent predictive value (OR: 1.22, 95% CI 1.08–1.38) to identify patients with high probability of HFpEF. Conclusions: Reservoir LAS shows a high diagnostic performance to distinguish HFpEF from non-cardiac causes of dyspnea in symptomatic patients with paroxysmal AF.

Background Deferring percutaneous coronary intervention (PCI) in patients with non-ischemic coronary stenoses based on fractional flow reserve (FFR) and preserved left ventricular ejection fraction (LVEF) is associated with favorable long-term clinical outcomes. In patients with reduced LVEF, the role of reversible/residual ischemia in deferring revascularization is still debated. Purpose To investigate whether FFR provides additive clinical benefit compared to coronary angiography in deferring revascularization in patients with intermediate coronary stenoses and reduced LVEF. Methods Among 4577 coronary angiographies performed between 2002 and 2010, consecutive patients with reduced LVEF (≤50%) and at least one intermediate coronary stenosis [diameter stenosis (DS)% 40–70%] in whom revascularization was deferred based either on FFR (FFR-guided) or angiography (Angiography-guided) were screened. The primary endpoint of the study was cumulative incidence of death at 10 years. Results A total of 843 patients were included (209 in the FFR-guided and 634 in the Angio-guided group). Median clinical follow-up was 7.1 years (IQR 3.2–11.2 years). After 1:1 propensity score matching, baseline characteristics between the two groups were similar. All-cause death at 10 years was significantly lower in the FFR-guided compared with the Angiography-guided group (94 [45%] vs 115 [55%], HR 0.72 [95% CI 0.55–0.95], p Conclusions In patients with reduced LVEF and associated coronary artery disease, deferring revascularization of intermediate stenoses based on FFR is associated with lower incidence of death and MACCE at 10 years. Funding Acknowledgement Type of funding sources: None.

Funding Acknowledgements Type of funding sources: None. Background Male and female athletes present difference spectrum of cardiac remodelling related to their sport activity. However data in elite female athletes are scarce and mainly limited to echocardiography evaluation. Purpose The aim of the study was to assess gender difference in extreme cardiac remodelling in Olympic athletes engaged in endurance sport assessed by non-contrast Cardiovascular Magnetic Resonance including Mapping. Methods Olympic athletes engaged in endurance sport (rowing, canoeing, mid/long distance swimming) were examined with history, physical examination, 12-lead and exercise electrocardiogram, and echocardiography as part of their evaluation prior the Olympic games (Tokyo 2020). Athletes with unremarkable evaluation were undergone to non-contrast CMR including Mapping. The following parameters were calculated: indexed left ventricle (LV) and right ventricle (RV) end-diastolic (EDVi) and end-systolic volumes (ESVi), stroke volume (SVi), ejection fraction (EF), left and right atria area (LAAi and RAAi), LV Mass (Massi) and maximum wall thickness (MWT), RV/LV EDV ratio, spericity index [SI=(long axis diameter/2)3 * 4,187], myocardial native T1 (nT1) and T2 Mapping. Results 51 caucasian elite athletes (without difference in term of age, years of training and hours of training/week) were enrolled and 59% were male. Male showed greater LV EDVi (123 ± 28 ml vs 103 ± 10, p = 0.003), ESVi (55 ± 14 ml vs 44 ± 7, p = 0.001), SVi (68 ± 15 ml vs 59 ± 7, p = 0.023), Massi (76 ± 19 vs 57 ± 10, p Conclusions Male endurance Olympic athletes presented higher volumes and LV mass compared to their female counterparts, while atria dimension, systolic function and sphericity index did not differ. Ventricles showed balanced dilatation in both gender. Lower T1 value observed in male suggested cellular hypertrophy. Figure 1 showed CMR images in a male (top row) and a female (bottom row) Olympic athletes: 4 chamber end-diastolic and end-systolic frame and end-diastolic basal short axis (SAX) showed balanced dilatation. Graphs showed higher EDVi and Massi in male compared o female, no difference in sphericity index and lower native T1 mapping. Abstract Figure 1

Background Hyperemic absolute coronary blood flow (in mL/min) can be safely and reproducibly measured with intracoronary continuous thermodilution of saline at room temperature at an infusion rate of 20 mL/min. This study aims at assessing the best infusion rate to measure resting flow by thermodilution, i.e. low enough to avoid microvascular dilation but high enough to allow reliable thermodilution tracings Methods and results In 26 coronary arteries (24 patients) with angiographic non-significant stenoses, absolute flow was assessed by continuous saline thermodilution at infusion rates of 10 mL/min and 20 mL/min using a pressure/temperature sensored guide wire, a dedicated infusion catheter and a dedicated software. Average peak velocity (APV) was measured simultaneously using an intracoronary Doppler-wire. In addition, in a subgroup of 10 arteries, absolute flow and APV were also measured during saline infusion at 6 ml/min and 8 ml/min. In 26 coronary arteries there was no significance difference in the Pd/Pa and in the APV at baseline and during the infusion of saline at 10 ml/min (Pd/Pa: 0.94±0.057 vs 0.94±0.059, p=0.82; APV: 22.2±8.40 vs 23.2±8.39 cm/s, p=0.63). In contrast, at an infusion rate of 20 mL/min, we observed a significant decrease in Pd/Pa compared to baseline (0.85±0.089 vs 0.95±0.053 vs, respectively, p Conclusion Absolute resting coronary flow can be measured by intracoronary continuous thermodilution of saline at infusion rate of 8–10 ml/min. Funding Acknowledgement Type of funding source: None

Background Diagnosis of heart failure with preserved ejection fraction (HFpEF) in patients with dyspnea and paroxysmal atrial fibrillation (AF) is challenging. Speckle tracking-derived left atrial strain (LAS) provides an accurate estimate of left ventricular filling pressures and left atrial phasic function. However, data on clinical utility of LAS in patients with dyspnea and AF are scarce. Objective To assess relationship between LAS and probability of HFpEF in patients with dyspnea and paroxysmal AF. Methods The study included 205 consecutive patients (62±10 years, 58% males) with limiting dyspnea (NYHA ≥ II), paroxysmal AF and preserved LVEF (≥50%), who underwent speckle tracking echocardiography and natriuretic peptide (NT-proBNP) assessment during sinus rhythm. Patients with manifest ischemic heart or valve disease, and cardiomyopathy were excluded. Probability of HFpEF was estimated using H2FPEF and HFA-PEFF scores, which combine clinical characteristics, echocardiographic parameters and natriuretic peptides. Results A total of 61 (30%), 115 (56%) and 29 (14%) had respectively high, intermediate and low probability of HFpEF. Patients with high probability of HFpEF were significantly older, had higher body mass index, NT-proBNP, E/e', pulmonary artery pressure and larger LA volume index than patients in low-to-intermediate probability groups (all p Conclusions Reservoir LAS shows a strong independent association with probability of HFpEF in patients with dyspnea and paroxysmal AF. This advocates for more liberal use of LAS assessment to distinguish cardiac from non-cardiac dyspnea in patients with history of AF. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): International PhD programme in Cardiovascular Pathophysiology and Therapeutics (CardioPaTh).

Introduction The evaluation of functional significance in serial coronary lesions is crucial for achieving optimal clinical outcomes. In this setting, fractional flow reserve (FFR) measurements with pullback pressure recording can be helpful in assessing lesion functional significance. Purpose To describe the functional characteristics of angiography-defined serial coronary lesions using FFR-derived motorised pullback tracings, and to describe the Pullback Pressure Gradients (PPG) index - in these lesions. Methods Prospective, multicentre study with independent core laboratory analysis. Patients undergoing coronary angiography due to stable angina were enrolled. Serial lesions were defined angiographically as the presence of 2 or more narrowings with visual diameter stenosis >50% separated at least by 3 times the reference vessel diameter in the same coronary vessel. Continuous IV adenosine-FFR measurements were obtained using a motorised device at a speed of 1 mm/s. Pullback curves were assessed to determine the presence of focal step-ups (FFR >0.05 units over 20 mm). In addition, the PPGindex was computed for all vessels. PPGindex values close to 0 define functional diffuse disease whereas values close to 1 define focal disease. Results From a total of 159 vessels (117 patients), 25 vessels were adjudicated as presenting serial lesions (mean PPGindex 0.48±0.17, range 0.26–0.87). Two focal pressure step-ups were observed in 40% of the cases (n=10; mean PPGindex 0.59±0.17), whereas 8% of the vessels presented a progressive pressure losses (n=2; mean PPGindex 0.27±0.01). In the remaining 52% of the cases, a single pressure step-up was recorded (n=13; mean PPGindex 0.44±0.12; ANOVA p-value = 0.01). The PPGindex independently predicted the presence of two focal pressure step ups. Conclusion Hyperemic FFR curves in tandem stenoses revealed high prevalence of functional diffuse CAD. Two pressure step-ups occurred in less than half of the vessels. High PPG-Index identified vessels with two focal pressure drops. FFR tracings and the PPGindex provide a more objective CAD evaluation, which can lead to changes in the therapeutic approach. Funding Acknowledgement Type of funding source: None

Background and aim Hyperemic absolute coronary blood flow (in mL/min) can be safely and reproducibly measured with intracoronary continuous thermodilution of saline at room temperature at an infusion rate of 20 mL/min. This study aims at assessing whether continuous thermodilution can also measure resting flow and microvascular resistance. Methods and results In 87 coronary arteries (58 patients) with angiographic non-significant stenoses absolute flow was assessed by continuous thermodilution of saline at infusion rates of 10 mL/min and 20 mL/min using a pressure/temperature sensored guide wire, a dedicated infusion catheter and a dedicated software. In addition, in 26 arteries, average peak velocity (APV) was measured simultaneously using an intracoronary Doppler-wire. There was no significant difference between Pd/Pa at baseline and during saline infusion at 10 mL/min, (0.95±0.053 vs 0.94±0.054, respectively (p=0.53) and there was no significant difference in APV at baseline and during the infusion of saline at 10 mL/min (22.2±8.40 vs 23.2±8.39 cm/s, respectively, p=0.63), thus indicating presence of resting coronary blood flow during the infusion of 10 mL/min of saline. In contrast, at an infusion rate of 20 mL/min, a significant decrease in Pd/Pa was observed compared to baseline: (0.85±0.089 vs 0.95±0.053, respectively, p Conclusion Absolute coronary blood flow (in mL/min) can be measured by continuous thermodilution both at rest and during hyperemia. This allows accurate, reproducible, and operator-independent direct volumetric calculation of CFR and MRR. The latter is a quantitative metric which is specific for microvascular function and independent from myocardial mass. Doppler and Thermodilution derived MRR Funding Acknowledgement Type of funding source: None

Purpose Hypovitaminosis D is a highly spread condition correlated with increased risk of respiratory tract infections. Nowadays, the world is in the grip of the Coronavirus disease 19 (COVID 19) pandemic. In these patients, cytokine storm is associated with disease severity. In consideration of the role of vitamin D in the immune system, aim of this study was to analyse vitamin D levels in patients with acute respiratory failure due to COVID-19 and to assess any correlations with disease severity and prognosis. Methods In this retrospective, observational study, we analysed demographic, clinical and laboratory data of 42 patients with acute respiratory failure due to COVID-19, treated in Respiratory Intermediate Care Unit (RICU) of the Policlinic of Bari from March, 11 to April 30, 2020. Results Eighty one percent of patients had hypovitaminosis D. Based on vitamin D levels, the population was stratified into four groups: no hypovitaminosis D, insufficiency, moderate deficiency, and severe deficiency. No differences regarding demographic and clinical characteristics were found. A survival analysis highlighted that, after 10 days of hospitalization, severe vitamin D deficiency patients had a 50% mortality probability, while those with vitamin D ≥ 10 ng/mL had a 5% mortality risk (p = 0.019). Conclusions High prevalence of hypovitaminosis D was found in COVID-19 patients with acute respiratory failure, treated in a RICU. Patients with severe vitamin D deficiency had a significantly higher mortality risk. Severe vitamin D deficiency may be a marker of poor prognosis in these patients, suggesting that adjunctive treatment might improve disease outcomes.

Background Revascularization decisions regarding left main (LM) coronary stenoses are often very challenging. Non-invasive tests can yield false negative results. On the other hand, some technical aspects of fractional flow reserve (FFR) measurement, as well as the interpretation of their results, are less codified than for other coronary segments. Purpose To investigate the 10-year clinical outcome of patients with isolated angiographically intermediate LM coronary stenosis in whom the treatment strategy was based on Fractional Flow Reserve (FFR) measurements. Methods From 1999 to 2009 we included 96 patients with isolated intermediate LM coronary disease (DS% 30–70%) evaluated with FFR measurement. When FFR was >0.80, patients were deferred to medical therapy (Deferral-group, n=71). When FFR was ≤0.8, surgical revascularization therapy was proposed (Revascularization-group, n=25). Death, the occurrence of myocardial infarction (MI) and the need for target vessel revascularization (TVR) were evaluated in both groups. Results There were no significant differences in clinical characteristics between the 2 groups. Mean DS% was 35% in the Deferral-group and 43% in the Revascularization-group (p Conclusions The use of FFR to defer revascularization in patients with non-significant isolated LM stenosis is safe and is associated with favourable clinical outcome at 10 years.

Introduction A pulmonary capillary wedge pressure (PCWP) ≥25 mm Hg following volume load or exercise has been proposed as a partition value for detection of HfpEF. However, the hemodynamic response to volume challenge in heart transplant (Tx) recipients has never been studied. Methods 24 heart Tx recipients (age: 65 years) with normal LV function (55±7%) and without rejection and graft vasculopathy underwent right heart catheterization to measure hemodynamic response to volume loading before and after a rapid saline infusion of 7mL/kg over 10 min. PCWP, right atrial pressure (RAP), mean pulmonary artery pressure (AP) were obtained and the PCWP and indexed (i) stroke volume (SV) data were used to construct Starling (SVindex/PCWP) curves. Pts were categorized in those with elevated filling pressures (Group A, n=13 pts) defined by a PCWP ≥15 mm Hg at rest or ≥25 mm Hg following volume loading vs those without (Group B, n=11 pts). Results No difference in age of donor and transplant heart, baseline hemodynamics and EF was noted between both groups. Saline infusion significantly increased PCWP and mean AP in both Groups (table 1) without any significant change in BP and heart rate. Interestingly saline infusion was associated with a significant rise in SV and SVi in Group B not in Group A pts. Moreover, in Group B pts the Starling curves revealed a larger SVi at any give PCWP compared to Group A pts (Fig.1). Table 1 All (n=24) Group A (n=13) Group B (n=11) Baseline Volume Loading Baseline Volume Loading Baseline Volume Loading RAP (mm Hg) 5.3±4.1 9.2±4.8* 7.6±4.8 11.4±5.2* 3.8±2.5 7.3±1.9* Mean AP 18.4±5.4 24.1±5.9* 21.7±5.1 26.8±6.5** 14.9±2.4 20.8±2.6* PCWP 12.1±4.9 16.8±6.7* 15.0±4.9 19.8±6.5** 8.4±1.9 14.6±3.7* SV 71.4±19.6 72.5±23.6 73.2±6.2 72.4±6.2 69.2±14.6 79.2±3.9 SViml/m2) 37.4±9.2 37.9±11.2 36.7±7.1 38.7±9.9 35.3±6.0 40.5±5.2* *p Figure 1 Conclusions In the transplanted heart volume loading increases filling pressures and is able to unmask left ventricular diastolic dysfunction. Interestingly, those with HFpEF are characterized by a blunted Frank Starling response as evidenced by higher PCWP and failure to increase SV for any given PCWP. Further prospective studies are warranted to unravel the underlying mechanisms.

Background In diabetic patients with multivessel coronary disease (MVD), coronary artery bypass grafting (CABG) has shown long-term benefits in mortality over percutaneous coronary revascularization (PCI). Nevertheless, the impact of fractional flow reserve (FFR)-guided PCI on clinical outcomes has never been investigated in these patients. Purpose To evaluate the long-term (5-year) clinical outcome of diabetic patients with MVD treated with FFR-guided PCI compared to CABG. Methods From February 2010 to February 2018, all diabetic patients undergoing coronary angiography in one centre (n=4622) were screened for inclusion. The inclusion criterion was presence of at least two-vessels CAD defined as with diameters stenosis ≥50%. In case of intermediate coronary stenosis (%DS 30–70%), FFR was performed at the discretion of the operator. Revascularization was performed when FFR ≤0.80. Exclusion criteria were ST-elevation myocardial infarction, prior CABG, and moderate or severe valvular heart dysfunction. To account for confounders, we compared outcomes by calculating an adjusted Kaplan-Meier estimator using inverse probability of treatment weighting (IPTW). Propensity score variables included age, sex, smoking habit, hypertension, hyperlipidemia, insulin therapy, family history of CAD, chronic obstructive pulmonary disease (COPD), glomerular filtration rate (GFR), prior myocardial infarction, peripheral vascular disease (PVD), admission for NSTEMI, ejection fraction, number of angiographic stenotic vessels. Odds ratios were calculated using generalized linear models (GLM). The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), defined as all-cause death, myocardial infarction and stroke. Secondary endpoints were the individual component of MACCE and any repeated revascularization. Results A total of 538 diabetic patients with MVD were included in the analysis. Among them, 317 (59%) patients underwent CABG and 221 (41%) FFR-guided PCI. Patients treated with FFR-guided PCI had more often COPD as compared to patients in the CABG-group, but patients treated with CABG had lower GFR, more PVD, higher number of angiographic stenotic vessels (2.8±0.4 vs. 2.5±0.5; p Clinical follow-up was obtained in 95% of the patients at a median follow-up of 5 years. The incidence of MACCE was similar in the CABG and in the FFR-guided PCI group [27% vs. 29%; OR (95% CI) 1.05 (0.68–1.63); p=0.74]. No differences were found in the individual components of MACCE. Repeat revascularization was more frequent in the FFR-guided PCI group than in the CABG group [27% vs. 7%; OR (95% CI) 4.3 (2.35–7.9); p Conclusions In diabetic patients with MVD undergoing FFR-guided PCI, no differences in major adverse events were observed at a median follow-up of 5 years compared with CABG.

Background Randomised controlled trials have confirmed the clinical benefit of invasive functional assessment to guide clinical decision making about myocardial revascularisation in patients with stable coronary artery disease. Treatment decision is based on one FFR value which provides a vessel-level metric as a surrogate of myocardial ischaemia. Also, the distribution of epicardial conductance can be evaluated using an FFR pullback manoeuvre. Purpose The objective of the present study is to characterise the physiological patterns of CAD using motorised coronary pressure pullbacks during continuous hyperaemia in patients with stable coronary artery disease. Methods Prospective, multicentre study of patients undergoing clinically-indicated coronary angiography. A pullback device, adapted to grip the coronary pressure wire, was set at a speed of 1 mm/sec. The pattern of CAD was adjudicated by visual inspection of the FFR pullback curves as focal, diffuse, or a combination of both mechanisms. Also, a quantitative classification of the physiological pattern of CAD was performed based on (1) the functional contribution of the epicardial lesion in relation to the total vessel FFR (Δlesion FFR/Δvessel FFR) and (2) the length (mm) of epicardial coronary segments with FFR drops in relation to the total vessel length. The combination of these two ratios, namely, lesion-related pressure drops (%FFR-lesion), and the extent of functional disease, resulted in the functional outcomes index (FOI), a metric that represents the pattern of CAD (i.e. focality or diffuseness) based on coronary physiology. Agreement on CAD patterns and between observers was assessed using Fleiss' Kappa. Analysis of variance (ANOVA) was used to compared quantitative variables. Correlation between variables was assessed by the Pearson moment coefficient. Results One hundred and fifty-eight vessels were included; 984,813 FFR values were used to generate the FFR pullback curves. Using motorised FFR pullbacks, 34% of the vessel disease patterns (i.e. focal, diffuse or combined) were reclassified compared to conventional angiography. The mean contribution of the angiographic lesions to the distal FFR (%FFR-lesion) was 61.7±25% whereas vessel length with the physiological disease was 59.8±21% of the total vessel length. The mean FOI was 0.61±0.17, and differentiated focal from diffuse CAD in terms of %FFR-lesion (p Conclusion Coronary angiography was inaccurate to assess the patterns of CAD. The inclusion of the functional component reclassified 34% of the vessel disease patterns (i.e. focal, diffuse or combined). A new metric, the FOI, based on the functional impact of anatomical lesions and the extent of physiological disease, discriminated focal from diffuse CAD. Further clinical trials are required to evaluate the usefulness of FOI for clinical decision making and outcomes.

Background The optimal PCI technique for bifurcation lesions remains a matter of debate. Several RCT have compared different bifurcation PCI techniques. Provisional stenting has been recommended as the default technique for most bifurcation lesions. However, emerging data suggests that double-kissing crush technique can be considered in true left main bifurcation lesions and has been endorsed by the European Society of Cardiology Guidelines. Purpose To compare the clinical outcome between different bifurcation PCI techniques. Methods We searched MEDLINE for randomized clinical trials (RCT) comparing PCI bifurcation techniques for coronary bifurcation lesions. Outcomes of interest were major adverse cardiovascular events (MACE) defined as the composite of cardiac death, myocardial infarction (MI) and target vessel or lesion revascularization (TVR/TLR), and the individual components of MACE. Stent thrombosis was assessed as defined by the ARC. Stratification based on left-main or distal bifurcations was performed. We evaluated the studies' risk of bias in accordance to the Cochrane Handbook for Systematic Reviews of Interventions, and certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework. We estimated summary odds ratios (ORs) using pairwise and Bayesian network meta-analysis. Results We identified 263 studies and of these included 19 RCT including 5572 patients treated with 5 bifurcation PCI techniques namely provisional stenting, systematic T-stenting, crush, culotte and double-kissing crush. Median follow-up was 12 months (IQR 8 to 36). When all bifurcation lesions were combined, double-kissing crush technique reduced the occurrence of MACE (OR 0.42; CrI 0.28 to 0.61) compared to provisional stenting. This difference was driven by a reduction in TVR/TLR (OR 0.39; CrI 0.25 to 0.65). No differences were found in cardiac death, MI or stent thrombosis among analyzed PCI techniques. No differences in MACE were observed between provisional stenting, systematic T-stenting, crush. In distal bifurcations (n=17 studies, 4634 patients), double-kissing crush also showed to reduce MACE (OR 0.48; CrI 0.29 to 0.67 vs. Provisional). In left-main bifurcations (n=3 studies, 938 patients) no differences in MACE were found between PCI techniques. Conclusions In this network meta-analysis, PCI bifurcation techniques were similar with respect to the occurrence of cardiac death, myocardial infarction and stent thrombosis. When all coronary bifurcations were combined, an advantage of double-kissing crush was observed in terms of MACE driven by lower rate of repeated revascularization. Further studies are required to define the best PCI bifurcation technique for left main coronary artery disease.

Study objectives: Hypertonic saline solution inhalation is suspected to produce airway inflammation. Design: The aim of this study was to verify this hypothesis by measuring inflammatory markers in exhaled breath condensate (EBC) collected before and after sputum induction with hypertonic and isotonic saline solution. Patients and methods: We enrolled 10 patients with asthma, 10 patients with COPD, and 7 healthy subjects with no history of lung disease. Levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α were measured in EBC by a specific enzyme immunoassay kit. Exhaled pH was measured after deaeration/decarbonation by bubbling with argon (350 mL/min) for 10 min by means of a pH meter. Measurements and results: Exhaled IL-6 and TNF-α concentrations were greater and pH was decreased compared to baseline after hypertonic saline solution inhalation in each group of subjects studied. No changes were observed following isotonic saline solution inhalation. Concentrations of IL-6, TNF-α, and pH in EBC correlated. Conclusions: These findings suggest that hypertonic saline solution inhalation could cause a low-grade inflammation in airways, and levels of inflammatory markers such as IL-6, TNF-α, and pH in EBC may be a useful noninvasive way to assess and monitor airway inflammation.

Background Despite recent encouraging results, the use of noninvasive ventilation (NIV) in the management of acute exacerbations in chronic obstructive pulmonary disease (COPD), complicated by acute respiratory failure (ARF), is not always successful. Failure of NIV may require an immediate intubation after a few hours (usually 1–3) of ventilation (‘early failure’) or may result in clinical deterioration (one or more days later) after an initial improvement of blood gas tension and general conditions (‘late failure’). Materials and methods We enrolled 122 patients affected by COPD complicated by ARF, and treated with NIV. The schedule of NIV provided sessions of 2–6 h twice daily. Results Ninety-nine (81%) patients showed a progressive improvement of the clinical parameters and were discharged. Among the remaining 23 patients, 13 had an early failure and 10 had a late failure. In the ‘success’ group and ‘late failure’ groups we found after an increase of pH 2 h of NIV (from 7·31 ± 0·05 to 7·38 ± 0·04 P

Objectives: Few papers addressed the gender difference in the polisomnographic features of obstructive sleep apnea (OSA). In this paper we investigated the sleep architecture and the nocturnal respiratory pattern in a group of severely obese women with OSA compared with a group of men with OSA matched by age and weight.Design: A cross-sectional study.Setting: Primary-care setting.Subjects, main outcome measures: Anthropometric parameters, respiratory function data and a full night polisomnography were evaluated in a group of 45 obese subjects, 20 females and 25 males, with a previous diagnosis of OSA.Results: The group of the severely obese women with OSA presented greater disturbances of the sleep architecture than the group of the men does (wake time after sleep onset 92.6±52.4 vs 58.2±45.2min, P

Carpagnano GE, Resta O, Ventura MT,Amoruso AC, Di Gioia G, Giliberti T, Refolo L,Foschino-Barbaro MP (University of Foggia; andUniversity of Bari; Italy). Airway inflammationin subjects with gastro-oesophageal reflux andgastro-oesophageal reflux-related asthma. J InternMed 2006; 259: 323–331.Study objectives. Asthma and gastro-oesophagealreflux (GER) are both characterized by airwayinflammation.Design. The purposes of this work were (i) to studyairway inflammation in patients troubled by gastro-oesophageal reflux (GER) and GER associated withasthma, (ii) to ascertain whether GER can aggravateasthma by exacerbating the pre-existing airwayinflammation and oxidative stress and (iii) toestablish the validity of analysing breathcondensate and induced sputum when studyingthe airways of subjects affected by GER.Patients and methods. We enrolled 14 patientsaffected by mild asthma associated with GER (40 ±12 years), nine with mild but persistent asthma(39 ± 13 years), eight with GER (35 ± 11 years)and 17 healthy subjects (37 ± 9 years). Sputum cellcounts andconcentrationsofinterleukin-4 (IL-4), IL-6 and 8-isoprostane were measured in breathcondensate and supernatant.Measurements and results. GER-related asthma ischaracterized by an eosinophilic inflammation, asdetermined by elevated concentrations of IL-4 inbreath condensate and sputum supernatant, and bysputum cell analysis. GER alone presents aneutrophilic pattern of inflammation whendetermined by elevated concentrations of IL-6 insputum cell analysis. A concomitant increase hasbeen found in 8-isoprostane in GER associated (ornot associated) with asthma.Conclusions. We conclude that GER is characterizedby a neutrophilic airway inflammation and byincreased oxidative stress. GER does not howeveraggravate pre-existing airway inflammation inasthma patients. Determinations of inflammatoryand oxidant markers in the breath condensate ofsubjects with GER reflect these measured in theinduced sputum.Keywords: asthma, breath condensate, gastro-oesophageal reflux, induced sputum, airwayinflammation, oxidative stress.

Background and Aim: To evaluate the prevalence of previously unknown hypothyroidism in adult male and female patients with a wide range of body mass index (BMI) values, referred to a Sleep Clinic because of sleep disordered breathing (SDB). Methods and Results: Serum concentrations of thyroid stimulating hormone (TSH) and free thyroxin (fT 4 ), as well as forced vital capacity (FVC), PaO 2 , PaCO 2 , the Epworth sleepiness scale (ESS), respiratory disturbance index (RDI), loud snoring, and the percentage of total sleep time (TST) with SaO2 ) were measured in 78 overweight and obese adult subjects with no previous diagnosis of hypothyroidism (age: 18–72 years). The prevalence of previously undiagnosed subclinical hypothyroidism in the population as a whole was 11.5%. BMI, TSH and ESS were significantly higher in the hypothyroid than the euthyroid subjects, but there was no significant between-group difference in RDI, TST SaO2 or the other investigated variables, including the prevalence of obstructive sleep apnea (OSA). Among the hypothyroid individuals, BMI, neck circumference, ESS, RDI and TST SaO2 were significantly higher in those with than in those without OSA. Furthermore, there was a clear trend towards a lower FVC% and higher snoring score in the OSA patients. Conclusions: Our results demonstrate a higher prevalence of hypothyroidism than that commonly reported in overweight and obese individuals referred to a Sleep Clinic for polysomnography because of SDB, thus suggesting that thyroid function should be evaluated in all obese patients suffering from SDB despite economic concerns.

In this paper we propose the use of immune network model for designing associative memories. Particularly, we show how the model of an immune system can be applied to the associative memorization problem, by defining an appropriate type of recruitment mechanism. Simulation results are shown to compare favourably with those produced from an other well-known model.

An intrinsic membrane protein of brain synaptic vesicles with Mr 38,000 (p38, synaptophysin) has recently been partially characterized (Jahn, R., W. Schiebler, C. Ouimet, and P. Greengard, 1985, Proc. Natl. Acad. Sci. USA, 83:4137-4141; Wiedenmann, B., and W. W. Franke, 1985, Cell, 41:1017-1028). We have now studied the presence of p38 in a variety of tissues by light and electron microscopy immunocytochemistry and by immunochemistry. Our results indicate that, within the nervous system, p38, like the neuron-specific phosphoprotein synapsin I, is present in virtually all nerve terminals and is selectively associated with small synaptic vesicles (SSVs). No p38 was detectable on large dense-core vesicles (LDCVs). p38 and synapsin I were found to be present in similar concentrations throughout the brain. Outside the nervous system, p38 was found in a variety of neuroendocrine cells, but not in any other cell type. In neuroendocrine cells p38 was localized on a pleiomorphic population of small, smooth-surfaced vesicles, which were interspersed among secretory granules and concentrated in the Golgi area, but not on the secretory granules themselves. Immunoblot analysis of endocrine tissues and cell lines revealed a band with a mobility slightly different from that of neuronal p38. This difference was attributable to a difference in glycosylation. The finding that p38, like synapsin I, is a component of SSVs of virtually all neurons, but not of LDCVs, supports the idea that SSVs and LDCVs are organelles of two distinct pathways for regulated neuronal secretion. In addition, our results indicate the presence in a variety of neuroendocrine cells of an endomembrane system, which is related to SSVs of neurons but is distinct from secretory granules.

Nerve endings of the posterior pituitary are densely populated by dense-core neurosecretory granules which are the storage sites for peptide neurohormones. In addition, they contain numerous clear microvesicles which are the same size as small synaptic vesicles of typical presynaptic nerve terminals. Several of the major proteins of small synaptic vesicles of presynaptic nerve terminals are present at high concentration in the posterior pituitary. We have now investigated the subcellular localization of such proteins. By immunogold electron microscopy carried out on bovine neurohypophysis we have found that three of these proteins, synapsin I, Protein III, and synaptophysin (protein p38) were concentrated on microvesicles but were not detectable in the membranes of neurosecretory granules. In addition, we have studied the distribution of the same proteins and of the synaptic vesicle protein p65 in subcellular fractions of bovine posterior pituitaries obtained by sucrose density centrifugation. We have found that the intrinsic membrane proteins synaptophysin and p65 had an identical distribution and were restricted to low density fractions of the gradient which contained numerous clear microvesicles with a size range the same as that of small synaptic vesicles. The peripheral membrane proteins synapsin I and Protein III exhibited a broader distribution extending into the denser part of the gradient. However, the amount of these proteins clearly declined in the fractions preceding the peak of neurosecretory granules. Our results suggest that microvesicles of the neurohypophysis are biochemically related to small synaptic vesicles of all other nerve terminals and argue against the hypothesis that such vesicles represent an endocytic byproduct of exocytosis of neurosecretory granules.

The presence and localization of synapsin I were investigated in the cat vestibular epithelium, using a rabbit anti-synapsin I antibody. The staining was performed by immunofluorescence or by a peroxidase—anti-peroxidase technique. A strong immunoreactivity was observed with both methods. It appeared as spherical patches distributed in the lower part of the epithelium. This distribution pattern is very similar to that of the efferent synaptic endings which are filled with microvesicles. Elongated immunoreactive segments were also observed around some hair cells. They suggest the presence of synapsin I in the afferent sensory endings contacting the hair cells. This immunoreactivity occurs in early postnatal and adult stages.

Background and Aim. Nasal polyposis (NP) occurs in about 1-4% of the worldwide population. Increased plasma concentrations of different pro-inflammatory cytokines have been observed in NP, and might be related to the pathogenesis of this syndrome.The present study was designed to investigate IL-6 and IL-4 concentrations in nasal and oral exhaled breath condensate of patients with early and advanced NP, and following polypectomy. Methods. Ten individuals with polyposis in early status, twenty-three patients affected by advanced status of NP and ten healthy controls were enrolled into the study. Exhaled breath condensate was collected by all individuals, according to a previous standardised method. An immunoassay kit was used to measure IL-6 and IL-4 levels. Results. Concentrations of oral and nasal exhaled IL- 6 and IL-4 were significantly higher in patients with early nasal polyposis and advanced nasal polyposis, compared to healthy controls. A statistically significant decrease of nasally but not of orally exhaled IL-6 (p

Background. Patients with obstructive sleep apnoea syndrome (OSAS) suffer from disrupted sleep. Impaired nightly sleep leads to increase physical and mental fatigue. The effect of long term continuous positive airway pressure (CPAP) on mental fatigue in OSAS patients, assessed by Maastricht Questionnaire (MQ), has not been investigated yet. Methods. In order to evaluate the role of CPAP in improving mental fatigue of patients with OSAS, we studied 35 patients (26 males, age