Chest CT opportunistic biomarkers for phenotyping high-risk COVID-19 patients: a retrospective multicentre study.

OBJECTIVE: To assess the value of opportunistic biomarkers derived from chest CT performed at hospital admission of COVID-19 patients for the phenotypization of high-risk patients. METHODS: In this multicentre retrospective study, 1845 consecutive COVID-19 patients with chest CT performed within 72 h from hospital admission were analysed. Clinical and outcome data were collected by each center 30 and 80 days after hospital admission. Patients with unknown outcomes were excluded. Chest CT was analysed in a single core lab and behind pneumonia CT scores were extracted opportunistic data about atherosclerotic profile (calcium score according to Agatston method), liver steatosis (≤ 40 HU), myosteatosis (paraspinal muscle F < 31.3 HU, M < 37.5 HU), and osteoporosis (D12 bone attenuation < 134 HU). Differences according to treatment and outcome were assessed with ANOVA. Prediction models were obtained using multivariate binary logistic regression and their AUCs were compared with the DeLong test. RESULTS: The final cohort included 1669 patients (age 67.5 [58.5-77.4] yo) mainly men 1105/1669, 66.2%) and with reduced oxygen saturation (92% [88-95%]). Pneumonia severity, high Agatston score, myosteatosis, liver steatosis, and osteoporosis derived from CT were more prevalent in patients with more aggressive treatment, access to ICU, and in-hospital death (always p < 0.05). A multivariable model including clinical and CT variables improved the capability to predict non-critical pneumonia compared to a model including only clinical variables (AUC 0.801 vs 0.789; p = 0.0198) to predict patient death (AUC 0.815 vs 0.800; p = 0.001). CONCLUSION: Opportunistic biomarkers derived from chest CT can improve the characterization of COVID-19 high-risk patients. CLINICAL RELEVANCE STATEMENT: In COVID-19 patients, opportunistic biomarkers of cardiometabolic risk extracted from chest CT improve patient risk stratification. KEY POINTS: • In COVID-19 patients, several information about patient comorbidities can be quantitatively extracted from chest CT, resulting associated with the severity of oxygen treatment, access to ICU, and death. • A prediction model based on multiparametric opportunistic biomarkers derived from chest CT resulted superior to a model including only clinical variables in a large cohort of 1669 patients suffering from SARS- CoV2 infection. • Opportunistic biomarkers of cardiometabolic comorbidities derived from chest CT may improve COVID-19 patients' risk stratification also in absence of detailed clinical data and laboratory tests identifying subclinical and previously unknown conditions.

Lipidomics analysis of monocytes from patients with acute myocardial infarction reveals lactosylceramide as a new player in monocyte migration.

Monocyte recruitment after vascular injury and their migration through the vessel wall represent crucial events in the initiation, progression, and destabilization of atherosclerotic plaque. Circulating monocytes are exposed to stimuli that alter their physiological state, and among them, lipids play a key role. Several studies investigated the mechanisms by which lipids affect monocyte functions promoting coronary atherosclerotic plaque initiation, but information on the relationship between lipid composition and function of monocyte is scant. We aimed at studying the migration of circulating monocytes isolated from patients with acute myocardial infarction (AMI) at hospital presentation and investigating its correlation with cellular lipid profile. The migration of monocytes was tested using both fetal bovine serum (FBS) and autologous serum as chemoattractant stimuli. Monocyte lipid profile was evaluated through an untargeted lipidomics approach, using a liquid chromatography/time-of-flight mass spectrometry platform. We observed that AMI patients' monocytes showed a significant increase in FBS and autologous serum-mediated migration compared to controls. Moreover, a different monocyte lipidomic profile between the two study groups was detected. In particular, AMI patients' monocytes showed an altered composition in ceramides, with an increase in lactosylceramide and in phospholipids (ie, phosphatidylethanolamine and lisophosphatidylethanolamine). Of note, a positive correlation between lactosylceramide levels and monocyte migration was observed. Furthermore, the lactosylceramide synthase inhibition significantly reduced FBS-induced monocyte migration. Our results highlight the influence of lactosylceramide on the monocyte migration capacity, pointing out a new possible mechanism of lipids in the onset of atherothrombosis and, hence, in AMI.

Associations of Preoperative Self-rated Symptoms of Anxiety and Depression on Length of Hospital Stay and Long-term Quality of Life in Patients Undergoing Cardiac Surgery.

BACKGROUND: Anxiety and depression are often associated with cardiovascular diseases. Nevertheless, few study authors have investigated psychological effects on immediate and long-term cardiac surgery-related outcomes, such as surgical complications, length of hospital stay (LOS), and long-term health-related quality of life (HRQoL). OBJECTIVES: The aims of this study were to (a) investigate the role of preoperative symptoms of anxiety and depression in predicting LOS in a sample of surgical patients and (b) evaluate the impact of preoperative symptoms of anxiety and depression on the patients' HRQoL 3 months after surgery. METHODS: One hundred fifty-one patients waiting for surgery were included. To evaluate symptoms of anxiety and depression, the Hospital Anxiety and Depression Scale was used. Multiple regression analyses were conducted to evaluate the impact of both clinical and psychological factors on LOS, whereas quantile regression was performed to assess their effect on the patients' HRQoL 3 months after surgery. RESULTS: The multiple regression shows that EuroSCORE, length of endotracheal intubation, and anxiety symptoms predict LOS. The multiple quantile regression analyses also show that both symptoms of anxiety and depression predict a negative HRQoL up to 3 months after surgery. CONCLUSION: Preoperative symptoms of anxiety predict the patients' LOS, and both symptoms of anxiety and depression predict a scarce HRQoL 3 months after cardiac surgery. These results suggest the need for implementing presurgical in-hospital screening procedures for both symptoms of anxiety and depression. Finally, focused psychological interventions should be implemented for reducing inpatients' hospital LOS and improving their future quality of life.

Mental health and risk perception among Italian healthcare workers during the second month of the Covid-19 pandemic.

A multicentre cross-sectional study was conducted to assess perceived risk and fear of contagion, as well as mental health outcomes among 650 Italian healthcare workers during the COVID-19 outbreak. A relevant proportion of the sample reported symptoms of anxiety, depression, and distress. Female sex, nursing profession, fear of being infected, as well as the time of exposure to the COVID-19 spread and the fact of directly attending infected patients were the main risk factors for developing mental health disturbances. Tailored interventions need to be implemented to reduce psychological burden in healthcare workers, with a particular attention to nurses.

Complete and Partial Lecithin:Cholesterol Acyltransferase Deficiency Is Differentially Associated With Atherosclerosis.

BACKGROUND: Lecithin:cholesterol acyltransferase (LCAT) is the sole enzyme that esterifies cholesterol in plasma. Its role in the supposed protection from atherogenesis remains unclear because mutations in LCAT causing fish-eye disease (FED) or familial LCAT deficiency (FLD) have been reported to be associated with more or instead less carotid atherosclerosis, respectively. This discrepancy may be associated with the loss of cholesterol esterification on only apolipoprotein AI (FED) or on both apolipoprotein AI- and apolipoprotein B-containing lipoproteins (FLD), an aspect that has thus far not been investigated. METHODS: Seventy-four heterozygotes for LCAT mutations recruited from Italy and the Netherlands were assigned to FLD (n=33) or FED (n=41) groups and compared with 280 control subjects. Subclinical atherosclerosis was assessed with carotid intima-media thickness. RESULTS: Compared with control subjects, total cholesterol was lower by 16% (-32.9 mg/dL) and 7% (-14.9 mg/dL) and high-density lipoprotein cholesterol was lower by 29% (-16.7 mg/dL) and 36% (-20.7 mg/dL) in the FLD and FED groups, respectively. Subjects with FLD displayed a significant 18% lower low-density lipoprotein cholesterol compared with subjects with FED (101.9±35.0 versus 123.6±47.4 mg/dL; P=0.047) and control subjects (122.6±35.0 mg/dL; P=0.003). Remarkably, all 3 intima-media thickness parameters were lower in subjects with FLD compared with FED and control subjects (accounting for age, sex, body mass index, smoking, hypertension, family history of cardiovascular disease, and plasma lipids). After additional correction for nationality and ultrasonographic methods, average and maximum intima-media thickness remained significantly lower when subjects with FLD were compared with those with FED (0.59 versus 0.73 mm, P=0.003; and 0.87 versus 1.24 mm, P<0.001, respectively). In contrast, the common carotid intima-media thickness (corrected for age, sex, body mass index, smoking, hypertension, family history of cardiovascular disease, and plasma lipids) was higher in subjects with FED compared with control subjects (0.69 versus 0.65 mm; P=0.05), but this significance was lost after adjustment for nationality and ultrasonographic machine. CONCLUSIONS: In this head-to-head comparison, FLD and FED mutations were shown to be associated with decreased and increased atherosclerosis, respectively. We propose that this discrepancy is related to the capacity of LCAT to generate cholesterol esters on apolipoprotein B-containing lipoproteins. Although this capacity is lost in FLD, it is unaffected in FED. These results are important when considering LCAT as a target to decrease atherosclerosis.

Extracellular volume fraction (ECV) derived from pre-operative computed tomography predicts prognosis in patients undergoing transcatheter aortic valve implantation (TAVI).

AIMS: Transcatheter aortic valve implantation (TAVI) is the treatment of choice for high-risk patients with severe aortic stenosis (AS). A portion of TAVI recipients has no long-term clinical benefit, and myocardial fibrosis may contribute to unfavourable outcomes. We aimed to assess the prognostic value of an interstitial fibrosis marker, extracellular volume fraction (ECV), measured at planning computed tomography (CT) before TAVI. METHODS AND RESULTS: From October 2020 to July 2021, 159 consecutive patients undergoing TAVI planning CT were prospectively enroled. ECV was calculated as the ratio of myocardium and blood pool differential attenuations before and 5 min after contrast administration, pondered for haematocrit. A composite endpoint including heart failure hospitalization (HFH) and death was collected by telehealth or in-person follow-up visits in the 113 patients constituting the final study population. Cox proportional hazards model was used to assess association between ECV and the composite endpoint.Median follow-up was 13 (11-15) months. The composite endpoint occurred in 23/113 (20%) patients. These patients had lower aortic valve mean pressure gradient [39 (29-48) vs. 46 (40-54) mmHg, P = 0.002] and left ventricular and right ventricular ejection fraction [51 (37-69) vs. 66 (54-74)%, P = 0.014; 45 (31-53) vs. 49 (44-55)%, P = 0.010] and higher ECV [31.5 (26.9-34.3) vs. 27.8 (25.3-30.2)%, P = 0.006]. At multivariable Cox analysis, ECV higher than 31.3% was associated to increased risk of death or HFH at follow-up (hazard ratio = 5.92, 95% confidence interval 2.37-14.75, P < 0.001). CONCLUSION: In this prospective observational cohort study, ECV measured at TAVI planning CT predicts the composite endpoint (HFH or death) in high-risk severe AS patients.

Examination of the best cut-off points of PHQ-2 and GAD-2 for detecting depression and anxiety in Italian cardiovascular inpatients.

OBJECTIVE: Despite the frequent association between anxiety, depression and cardiovascular diseases (CVD), cardiovascular inpatients are not usually screened for these psychopathological conditions. To fill this gap, especially in hospital environments, there is the need of brief screening instruments that provide reliable information in a very short time. According to this need, the aim of this study was to examine the best cut-off points of two brief and easy-to-use questionnaires in a sample of Italian cardiovascular inpatients: the 2-item Patient Health Questionnaire (PHQ-2) and the 2-item Generalized Anxiety Disorder (GAD-2). DESIGN: 3500 cardiovascular inpatients were recruited and completed both the 9-item Patient Health Questionnaire (PHQ-9) and the 7-item Generalized Anxiety Disorder (GAD-7). PHQ-2 and GAD-2 were then obtained extracting the first two item from PHQ-9 and GAD-7. MAIN OUTCOME MEASURES: The PHQ-2 and GAD-2 psychometric properties were calculated comparing them with PHQ-9 and GAD-7, respectively. RESULTS: The PHQ-2 threshold of ≥ 2 and the GAD-2 threshold of ≥ 3 are the best solutions in balancing between sensitivity and specificity, also providing acceptable rates of false positives and false negatives. CONCLUSIONS: the PHQ-2 and GAD-2 Italian versions showed good diagnostic features for measuring depression and anxiety in CVD patients.

Week to week variability of pulmonary capillary blood volume and alveolar membrane diffusing capacity in patients with heart failure.

BACKGROUND: Alveolar-capillary membrane diffusing capacity for carbon monoxide (DMCO) and pulmonary capillary volume (Vcap) can be estimated by the multi-step Roughton and Foster (RF, original method from 1957) or the single-step NO-CO double diffusion technique (developed in the 1980s). The latter method implies inherent assumptions. We sought to determine which combination of the alveolar membrane diffusing capacity for nitric oxide (DMNO) to DMCO ratio, an specific conductance of the blood for NO (θNO) and CO (θCO) gave the lowest week-to-week variability in patients with heart failure. METHODS: 44 heart failure patients underwent DMCO and Vcap measurements on three occasions over a ten-week period using both RF and double dilution NO-CO techniques. RESULTS: When using the double diffusing method and applying θNO = infinity, the smallest week-to-week coefficient of variation for DMCO was 10 %. Conversely, the RF method derived DMCO had a much greater week-to-week variability (2x higher coefficient of variation) than the DMCO derived via the NO-CO double dilution technique. The DMCO derived from the double diffusion technique most closely matched the DMCO from the RF method when θNO = infinity and DMCO = DLNO/2.42. The Vcap measured week-to-week was unreliable regardless of the method or constants used. CONCLUSIONS: In heart failure patients, the week-to-week DMCO variability was lowest when using the single-step NO-CO technique. DMCO obtained from double diffusion most closely matched the RF DMCO when DMCO/2.42 and θNO = infinity. Vcap estimation was unreliable with either method.

Netrin-1 in Atherosclerosis: Relationship between Human Macrophage Intracellular Levels and In Vivo Plaque Morphology.

Netrin-1 is a laminin-like protein that plays a pivotal role in cell migration and, according to the site of its release, exerts both pro and anti-atherosclerotic functions. Macrophages, key cells in atherosclerosis, are heterogeneous in morphology and function and different subpopulations may support plaque progression, stabilization, and/or regression. Netrin-1 was evaluated in plasma and, together with its receptor UNC5b, in both spindle and round monocyte-derived macrophages (MDMs) morphotypes from coronary artery disease (CAD) patients and control subjects. In CAD patients, plaque features were detected in vivo by optical coherence tomography. CAD patients had lower plasma Netrin-1 levels and a higher MDMs expression of both protein and its receptor compared to controls. Specifically, a progressive increase in Netrin-1 and UNC5b was evidenced going from controls to stable angina (SA) and acute myocardial infarction (AMI) patients. Of note, spindle MDMs of AMI showed a marked increase of both Netrin-1 and its receptor compared to spindle MDMs of controls. UNC5b expression is always higher in spindle compared to round MDMs, regardless of the subgroup. Finally, CAD patients with higher intracellular Netrin-1 levels showed greater intraplaque macrophage accumulation in vivo. Our findings support the role of Netrin-1 and UNC5b in the atherosclerotic process.

Potential Relation between Plasma BDNF Levels and Human Coronary Plaque Morphology.

Coronary artery disease (CAD) patients are at high ischemic risk, and new biomarkers reflecting atherosclerotic disease severity and coronary plaque vulnerability are required. The Brain-Derived Neurotrophic Factor (BDNF) affects endothelial and macrophage activation suggesting its involvement in atherosclerotic plaque behavior. To investigate whether plasma BDNF is associated with in vivo coronary plaque features, assessed by optical coherence tomography (OCT), in both acute myocardial infarction (AMI) and stable angina (SA) patients, we enrolled 55 CAD patients (31 SA and 24 AMI), and 21 healthy subjects (HS). BDNF was lower in CAD patients than in HS (p < 0.0001), and it decreased with the presence, clinical acuity and severity of CAD. The greater BDNF levels were associated with OCT features of plaque vulnerability in overall CAD as well as in SA and AMI patients (p < 0.03). Specifically, in SA patients, BDNF correlated positively with macrophages' infiltration within atherosclerotic plaque (p = 0.01) and inversely with minimal lumen area (p = 0.02). In AMI patients a negative correlation between BDNF and cap thickness was found (p = 0.02). Despite a small study population, our data suggest a relationship between BDNF and coronary plaque vulnerability, showing that vulnerable plaque is positively associated with plasma BDNF levels, regardless of the clinical CAD manifestation.

Persistent long-term platelet activation and endothelial perturbation in women with Takotsubo syndrome.

BACKGROUND: Takotsubo (TTS) syndrome is an acute cardiac condition characterized by transient and reversible left ventricle dysfunction that mainly affects postmenopausal women. Catecholamine burst is the most accredited mechanism underpinning TTS onset and leading to endothelial dysfunction and platelet activation. Even if the use of low dose acetylsalycilic acid (ASA) in this clinical setting is based on both clinical presentation and unfavorable long-term prognosis, its efficacy has been recently challenged. AIM: This study was designed to assess endothelial function, residual thromboxane formation and platelet aggregation in TTS women on low-dose ASA treatment at long-term follow-up. METHODS: Twenty-eight females with previously diagnosis of TTS syndrome were enrolled. Data were compared to those obtained from 23 coronary artery disease (CAD) women with a history of acute myocardial infarction, and 26 control subjects with no TTS or clinically evident CAD. Psychological and clinical profile were assessed in all study groups at the enrollment. Main metabolites involved in L-arginine/nitric oxide pathway, urinary prostacyclin, serum and urine thromboxane metabolites were measured by LCMS/MS methods. Thrombomodulin levels were quantified using an ELISA kit, and platelet aggregation, carried out on platelet rich-plasma, was induced by ADP or by epinephrine (EPI), norepinephrine (NORE) and TRAP-6, alone or in association with ADP and evaluated by Born's method. RESULTS: In TTS women an endothelial derangement, characterized by reduced citrulline production and increased thrombomodulin concentration, with no perturbation in prostacyclin levels, was evidenced. In addition, despite ASA treatment, TTS displayed a higher residual thromboxane formation, in parallel with an enhanced platelet response to compared to CAD. CONCLUSIONS: Our study highlighted the presence of endothelial perturbation in TTS patients even at long-term from the index event. The residual thromboxane production and platelet aggregation still leave open the question about the use of low dose ASA in this clinical setting.

Depressive and Anxiety Symptoms Screening in Cardiac Inpatients: A Virtuous Italian Approach to Psychocardiology.

Despite the fact that American Heart Association (AHA) recommended a systematic screening for depression in cardiovascular inpatients, poor attention has been given to this issue. Furthermore, no specific guidelines exist for anxiety screening in cardiovascular inpatients. Thus, the aims of this study were to verify the feasibility of a depressive and anxiety symptoms screening protocol in an Italian hospital specializing in cardiovascular diseases and to evaluate both anxiety and depressive symptoms prevalence. A group of 2009 consecutive inpatients completed the 9-item Patient Health Questionnaire (PHQ-9) and the 7-item Generalized Anxiety Disorder (GAD-7). The rates of depressive and anxiety symptoms were almost 9% and 16% respectively. Men were less likely than women to experience both depressive and anxiety symptoms. Patients who were admitted to the heart failure unit reported higher risk of experiencing both symptoms compared to patients in other wards. Similarly, patients admitted to the cardiac surgery unit showed a higher risk of experiencing anxiety symptoms compared to other patients. The proposed screening procedure showed a good feasibility and acceptance. This study highlighted the importance of implementing a short screening procedure in hospitals dealing with cardiovascular inpatients to identify those individuals who require specific attention and interventions.

Spontaneous Participation in Secondary Prevention Programs: The Role of Psychosocial Predictors.

Disease prevention is a multifaceted construct that has been widely studied. Nevertheless, in spite of its importance, it is still not sufficiently considered by the general population. Since the reasons for this lack of consideration are not yet fully understood, we created an Online Prevention Survey (OPS) to investigate the role of both sociodemographic and psychological factors in predicting individuals' spontaneous participation in secondary prevention programs. The results revealed that younger people, men, manual workers, unemployed people, and those who do not regularly practise physical activity were less likely to spontaneously participate in such programs. Furthermore, an analysis of the psychological determinants of the willingness to participate in secondary prevention programs showed that depressive symptoms negatively predict it, while an individual's perception of receiving high social support acts as a positive predictor. Based on these results, we suggest the need for implementing new tailored approaches to promote prevention initiatives to those segments of the population which are more reluctant to spontaneously undertake prevention paths.

Effects of ß2-receptor stimulation by indacaterol in chronic heart failure treated with selective or non-selective ß-blockers: a randomized trial.

Alveolar ß2-receptor blockade worsens lung diffusion in heart failure (HF). This effect could be mitigated by stimulating alveolar ß2-receptors. We investigated the safety and the effects of indacaterol on lung diffusion, lung mechanics, sleep respiratory behavior, cardiac rhythm, welfare, and exercise performance in HF patients treated with a selective (bisoprolol) or a non-selective (carvedilol) ß-blocker. Study procedures were performed before and after indacaterol and placebo treatments according to a cross-over, randomized, double-blind protocol in forty-four patients (27 on bisoprolol and 17 on carvedilol). No differences between indacaterol and placebo were observed in the whole population except for a significantly higher VE/VCO2 slope and lower maximal PETCO2 during exercise with indacaterol, entirely due to the difference in the bisoprolol group (VE/VCO2 31.8 ± 5.9 vs. 28.5 ± 5.6, p < 0.0001 and maximal PETCO2 36.7 ± 5.5 vs. 37.7 ± 5.8 mmHg, p < 0.02 with indacaterol and placebo, respectively). In carvedilol, indacaterol was associated with a higher peak heart rate (119 ± 34 vs. 113 ± 30 bpm, with indacaterol and placebo) and a lower prevalence of hypopnea during sleep (3.8 [0.0;6.3] vs. 5.8 [2.9;10.5] events/hour, with indacaterol and placebo). Inhaled indacaterol is well tolerated in HF patients, it does not influence lung diffusion, and, in bisoprolol, it increases ventilation response to exercise.

Red Blood Cell Morphodynamics: A New Potential Marker in High-Risk Patients.

In the last years, a substantial contribution of red blood cells (RBCs) in cardiovascular homeostasis has been evidenced, as these cells are able to regulate cardiovascular function by the export of adenosine triphosphate and nitric oxide as well as to maintain redox balance through a well-developed antioxidant system. Recently a link between high-risk plaque (HRP) features and myocardial ischemia, in the absence of severe lumen stenosis, has been evidenced. Nonobstructive coronary artery disease (nonob CAD) has been associated in fact with a greater 1-year risk of myocardial infarction and all-cause mortality compared with no apparent CAD. This new evidence increases interest in searching new triggers to identify these high-risk patients, in the absence/or on top of traditional hazard markers. In this study, we investigated the existence of any association between RBC morphodynamics and HRP features in individuals with different grades of coronary stenosis detected by coronary computed tomography angiography (CCTA). Ninety-one consecutive individuals who underwent CCTA [33 no CAD; 26 nonobstructive (nonob), and 32 obstructive (ob) CAD] were enrolled. RBC morphodynamic features, i.e., RBC aggregability and deformability, were analyzed by means of Laser Assisted Optical Rotation Cell Analyzer (LoRRca MaxSis). The putative global RBC morphodynamic (RMD) score and the related risk chart, associating the extent of HRP (e.g., the non-calcified plaque volume) with both the RMD score and the max % stenosis were computed. In nonob CAD group only positive correlations between RBC rigidity, osmotic fragility or aggregability and HRP features (plaque necrotic core, fibro-fatty and fibro-fatty plus necrotic core plaque volumes) were highlighted. Interestingly, in this patient cohort three of these RBC morphodynamic features result to be independent predictors of the presence of non-calcified plaque volume in this patients group. The risk chart created shows that only in nonob CAD plaque vulnerability increases according to the score quartile. Findings of this work, by evidencing the association between erythrocyte morphodynamic characteristics assessed by LoRRca and plaque instability in a high-risk cohort of nonob CAD, suggest the use of these blood cell features in the identification of high-risk patients, in the absence of severe coronary stenosis.

Variability in pulmonary diffusing capacity in heart failure.

BACKGROUND: As pulmonary diffusing capacity is related to mortality risk and prognosis in patients with heart failure (HF), it is measured frequently. As such, it would be essential to know the week-to-week variability (reproducibility) of pulmonary diffusing capacity for carbon monoxide (DLCO) and nitric oxide (DLNO). This variability would let clinicians understand what a clinically measurable change in DLCO and DLNO would be in these patients. METHODS: On three different days spanning over ten weeks, 40 H F patients underwent testing for DLCO and DLNO. DLCO was determined after a 4 s and 10 s breath-hold maneuver, while DLNO was determined after a 4 s breath-hold maneuver. RESULTS: Forty heart failure patients (66 ± 10 years; BMI = 28.4 ± 4.6 kg∙m-2; 28 males), that were referred to our clinic were able to complete the protocol. DLCO (4 s breath-hold) and DLNO (4 s breath-hold) were 79 ± 19 % and 59 ± 14 % predicted, respectively. Fifty percent of patients (n = 20) were below the lower limit of normal (LLN, below the 5th percentile) for predicted DLCO (4 s), while 78 % of patients (n = 31) were below the LLN for predicted DLNO. All 16 patients that were below the LLN for DLCO were also below the LLN for DLNO. Over a ten week period, the reproducibility of DLNO (4 s) DLCO (4 s) and DLCO (10 s) was 18.9, 8.2, and 5.9 mL min mmHg-1, respectively. CONCLUSIONS: The week-to-week fluctuation in DLNO (4 s), as a percentage, is less than DLCO (4 s) in patients with HF. The reproducibility of DLNO in patients with HF is like that of healthy subjects.

Iron deficiency in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

BACKGROUND: Iron deficiency (ID) is a known co-morbidity and a potential therapeutic target in heart failure. Whether ID is frequent also in ST-segment elevation acute myocardial infarction (STEMI) patients and is associated with worse in-hospital outcomes has never been evaluated. METHODS: We defined ID as a serum ferritin < 100 µg/L or transferrin saturation < 20% at hospital admission. We assessed the association between ID and the primary endpoint (a composite of in-hospital mortality and Killip class ≥ 3). We explored the potential association between ID, circulating cell-free mitochondrial DNA (mtDNA), and cardiac magnetic resonance (CMR) parameters. RESULTS: Four-hundred-twenty STEMI patients undergoing primary percutaneous coronary intervention (pPCI) were included. Of them, 237 (56%) had ID. They had significantly higher admission high-sensitivity troponin and mtDNA levels as compared to non-ID patients (145 ±â€¯35 vs. 231 ±â€¯66 ng/L, P < 0.001; 917 [404-1748] vs. 1368 [908-4260] copies/µL; P < 0.003, respectively). A lower incidence of the primary endpoint (10% vs. 18%, P = 0.01) was observed in ID patients (adjusted OR 0.50 [95% CI 0.27-0.93]; P = 0.02). At CMR (n = 192), ID patients had a similar infarct size (21 ±â€¯18 vs. 21 ±â€¯19 g; P = 0.95), but a higher myocardial salvage index (0.56 ±â€¯0.30 vs. 0.43 ±â€¯0.27; P = 0.002), and a smaller microvascular obstruction extent (3.6 ±â€¯2.2 vs. 6.9 ±â€¯3.9 g; P < 0.001). CONCLUSIONS: Iron deficiency is frequent in STEMI patients, it is coupled with mitochondrial injury, and, paradoxically, with a better in-hospital outcome. This unexpected clinical result seems to be associated with a smaller myocardial reperfusion injury. The mechanisms underlying our findings and their potential clinical implications warrant further investigation.

Aortic Valve Sclerosis Adds to Prediction of Short-Term Mortality in Patients with Documented Coronary Atherosclerosis.

AIMS: Aortic valve sclerosis (AVSc), a non-uniform thickening of leaflets with an unrestricted opening, is characterized by inflammation, lipoprotein deposition, and matrix degradation. In the general population, AVSc predicts long-term cardiovascular mortality (+50%) even after adjustment for vascular risk factors and clinical atherosclerosis. We have hypothesized that AVSc is a risk-multiplier able to predict even short-term mortality. To address this issue, we retrospectively analyzed 90-day mortality of all patients who underwent isolated coronary artery bypass grafting (CABG) at Centro Cardiologico Monzino over a ten-year period (2006-2016). METHODS: We analyzed 2246 patients and 90-day all-cause mortality was 1.5% (31 deaths). We selected only patients deceased from cardiac causes (n = 29) and compared to alive patients (n = 2215). A cardiologist classified the aortic valve as no-AVSc (n = 1352) or AVSc (n = 892). Cox linear regression and integrated discrimination improvement (IDI) analyses were used to evaluate AVSc in predicting 90-day mortality. RESULTS: AVSc 90-day survival (97.6%) was lower than in no-AVSc (99.4%; p < 0.0001) with a hazard ratio (HR) of 4.0 (95%CI: 1.78, 9.05; p < 0.0001). The HR for AVSc, adjusted for propensity score, was 2.7 (95%CI: 1.17, 6.23; p = 0.02) and IDI statistics confirmed that AVSc significantly adds (p < 0.001) to the identification of high-risk patients than EuroSCORE II alone. CONCLUSION: Our data supports the hypothesis that a risk stratification strategy based on AVSc, added to ESII, may allow better recognition of patients at high-risk of short-term mortality after isolated surgical myocardial revascularization. Results from this study warrant further confirmation.

Activation of Nrf2/HO-1 Pathway and Human Atherosclerotic Plaque Vulnerability:an In Vitro and In Vivo Study.

Reactive oxygen species (ROS) induce nuclear factor erythroid 2-related factor 2 (Nrf2) activation as an adaptive defense mechanism, determining the synthesis of antioxidant molecules, including heme-oxygenase-1 (HO-1). HO-1 protects cells against oxidative injury, degrading free heme and inhibiting ROS production. HO-1 is highly expressed in macrophages during plaque growth. Macrophages are morpho-functionally heterogeneous, and the prevalence of a specific phenotype may influence the plaque fate. This heterogeneity has also been observed in monocyte-derived macrophages (MDMs), a model of macrophages infiltrating tissue. The study aims to assess oxidative stress status and Nrf2/HO-1 axis in MDM morphotypes obtained from healthy subjects and coronary artery disease (CAD) patients, in relation to coronary plaque features evaluated in vivo by optical coherence tomography (OCT). We found that MDMs of healthy subjects exhibited a lower oxidative stress status, lower Nrf2 and HO-1 levels as compared to CAD patients. High HO-1 levels in MDMs were associated with the presence of a higher macrophage content, a thinner fibrous cap, and a ruptured plaque with thrombus formation, detected by OCT analysis. These findings suggest the presence of a relationship between in vivo plaque characteristics and in vitro MDM profile, and may help to identify patients with rupture-prone coronary plaque.

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

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