Neglected cardiometabolic risk factors and subclinical target organ damage in post-menopausal women with normal glucose tolerance.

BACKGROUND: Menopausal transition is a crucial step in the women's cardiovascular health, and the risk stratification in apparently health post-menopausal females has been rarely assessed. Heart ultrasonography, unusually performed in such subjects, would be able to detect initial signs of organ damage. We described the cardiovascular risk profile of non-diabetic post-menopausal women, evaluating how easily computed, biochemistry-derived scores were related to ultrasonographic measures of target organ damage. METHODS: We analyzed the characteristics of a cohort of two-hundred and seventy-three women consecutively referring to a prevention program of Azienda Ospedaliero-Universitaria Pisana (years 2017-2022) who underwent clinical evaluation, complete routine biochemical analyses with proxies of insulin resistance, heart and carotid ultrasonography. The cohort was further divided into four groups according to presence of isolated hypercholesterolemia (HC, 37%), isolated hypertension (HT, 5%), both HC/HT (38%), or none of them. RESULTS: In HC and HC/HT, LDL cholesterol was sharply above the recommended values (149 [134-171] mg/dL and 141 [123-159] mg/dL, respectively). E/e' ratio and left atrium size were augmented in HT women and further worsened in HT/HC, with an independent effect of hypertension (E/e' ß=0.055, P=0.013, left atrium volume ß=0.059, P=0.003). Presence of carotid plaques was independently linked to hypertension (ß=0.474, P=0.003). In HC and HC/HT, the Triglycerides-Glucose Index, a surrogate of insulin resistance, was higher than in the other classes (P=0.0013), and it was associated with E/A in HC and HT/HC, with a significative interaction (P=0.0004) with hypertension. Past hormone replacement therapy did not influence clinical, biochemical or echocardiographic parameters. CONCLUSIONS: Postmenopausal women display a high cardiovascular risk burden; a simple clinical and biochemistry screening would be advisable to identify and treat those more at risk. Cardiac ultrasonographic parameters were worse in hypertensive, hypercholesterolemic and insulin-resistant subjects, who may also deserve a deep and early instrumental characterization, especially when these conditions are associated.

Response to semaglutide of non-drinker subjects with type 2 diabetes.

BACKGROUND: Metabolic dysfunction-associated Steatotic Liver Disease (MASLD) displays a worse prognosis in subjects with type 2 diabetes (T2D); effective treatments are, so far, scanty. Semaglutide showed efficacy in improving steatohepatitis. We longitudinally observed a MASLD cohort of T2D subjects starting semaglutide, to detect an improvement of non-invasive surrogates of steatosis and fibro-inflammatory liver involvement, evaluating the role of mild alcohol consumption. PATIENTS AND METHODS: In 62 overweight/obese T2D subjects with MASLD (36 non-drinker and 26 mild alcohol consumers), anthropometric, bio-humoral and transient elastography (TE) data were collected before (T0) and after an average time of 6.4 month (T1) from injective semaglutide prescription. Circulating levels of hormones (GIP, GLP-1, glucagon, insulin) and inflammatory markers (TNFα, MCP-1, IL-18, IL-10) were measured. Steatotic and necro-inflammatory liver involvement was evaluated with FibroScan controlled attenuation parameter (CAP) and liver stiffness (LS), respectively. RESULTS: Significant (p < 0.006) T0-T1 reductions of BMI, waist circumference, fasting glucose, and HbA1c were observed. AST (-10 ± 3 IU/L), ALT (-18 ± 5 IU/L), GGT (-33 ± 15 IU/L), CAP (-25 ± 8 dB/m) and LS (-0.8 ± 0.4 kPa) were reduced, too. GLP-1 increased (+ 95.9 pM, p < 0.0001) and IL-18 was reduced (-46.6 pg/ml, p = 0.0002). After adjustment for confounders, CAP improving was only related to GLP-1 increase (ß=-0.437, p = 0.0122). Mild alcohol intake did not influence these relations. CONCLUSION: Use of semaglutide in subjects with T2D and MASLD is associated with a significant decline of liver steatosis and necroinflammation proxies; mild alcohol assumption did not exert any influence. An independent effect of GLP-1 raise was observed on reduction of steatosis, irrespective of alcohol consumption.

DEep LearnIng-based QuaNtification of epicardial adipose tissue predicts MACE in patients undergoing stress CMR.

BACKGROUND AND AIMS: This study investigated the additional prognostic value of epicardial adipose tissue (EAT) volume for major adverse cardiovascular events (MACE) in patients undergoing stress cardiac magnetic resonance (CMR) imaging. METHODS: 730 consecutive patients [mean age: 63 ± 10 years; 616 men] who underwent stress CMR for known or suspected coronary artery disease were randomly divided into derivation (n = 365) and validation (n = 365) cohorts. MACE was defined as non-fatal myocardial infarction and cardiac deaths. A deep learning algorithm was developed and trained to quantify EAT volume from CMR. EAT volume was adjusted for height (EAT volume index). A composite CMR-based risk score by Cox analysis of the risk of MACE was created. RESULTS: In the derivation cohort, 32 patients (8.7 %) developed MACE during a follow-up of 2103 days. Left ventricular ejection fraction (LVEF) < 35 % (HR 4.407 [95 % CI 1.903-10.202]; p<0.001), stress perfusion defect (HR 3.550 [95 % CI 1.765-7.138]; p<0.001), late gadolinium enhancement (LGE) (HR 4.428 [95%CI 1.822-10.759]; p = 0.001) and EAT volume index (HR 1.082 [95 % CI 1.045-1.120]; p<0.001) were independent predictors of MACE. In a multivariate Cox regression analysis, adding EAT volume index to a composite risk score including LVEF, stress perfusion defect and LGE provided additional value in MACE prediction, with a net reclassification improvement of 0.683 (95%CI, 0.336-1.03; p<0.001). The combined evaluation of risk score and EAT volume index showed a higher Harrel C statistic as compared to risk score (0.85 vs. 0.76; p<0.001) and EAT volume index alone (0.85 vs.0.74; p<0.001). These findings were confirmed in the validation cohort. CONCLUSIONS: In patients with clinically indicated stress CMR, fully automated EAT volume measured by deep learning can provide additional prognostic information on top of standard clinical and imaging parameters.

MRI pattern characterization of cerebral cardioembolic lesions following atrial fibrillation ablation.

Background: Recognizing etiology is essential for treatment and secondary prevention of cerebral ischemic events. A magnetic resonance imaging (MRI) pattern suggestive of an embolic etiology has been described but, to date, there are no uniformly accepted criteria. Aim: The purpose of the study is to describe MRI features of ischemic cerebral lesions occurring after transcatheter ablation of atrial fibrillation (AF). Methods: A systematic review and meta-analysis of studies performing brain imaging investigations before and after AF transcatheter ablation was performed. The incidence of cerebral ischemic lesions after AF transcatheter ablation was the primary endpoint. The co-primary endpoints were the prevalence of the different neuroimaging features regarding the embolic cerebral ischemic lesions. Results: A total of 25 studies, encompassing 3,304 patients, were included in the final analysis. The incidence of ischemic cerebral lesions following AF transcatheter ablation was 17.2% [95% confidence interval (CI) 12.2%-23.8%], of which a minimal fraction was symptomatic [0.60% (95% CI 0.09%-3.9%)]. Only 1.6% of the lesions (95% CI 0.9%-3.0%) had a diameter >10 mm, and in 20.5% of the cases the lesions were multiple (95% CI 17.1%-24.4%). Brain lesions were equally distributed across the two hemispheres and the different lobes; cortical location was more frequent [64.0% (95% CI 42.9%-80.8%)] while the middle cerebral artery territory was the most involved 37.0% (95% CI 27.3-48.0). Conclusions: The prevailing MRI pattern comprises a predominance of small (<10 mm) cortical lesions, more prevalent in the territory of the middle cerebral artery.

Myocardial Bridging: Review on the Role of Coronary Computed Tomography Angiography.

Myocardial bridging (MB) is a congenital coronary anomaly in which a segment of a coronary artery, most frequently the left anterior descending artery, deviates from its epicardial route by passing through the myocardium. The advent of cardiac computed tomography angiography (CCTA), equipped with its multiplane and three-dimensional functionalities, has notably enhanced the ability to identify MBs. Furthermore, novel post-processing methods have recently emerged to extract functional insights from anatomical evaluations. MB is generally considered a benign entity with very good survival rates; however, there is an increasing volume of evidence that certain MB characteristics may be associated with cardiovascular morbidity. This review is intended to depict the diagnostic and prognostic role of CCTA in the MB context.

Cardiac computed tomography: from anatomy to function.

Ischaemic heart disease (IHD) is one of the world's leading causes of morbidity and mortality. Likewise, the diagnosis and risk stratification of patients with coronary artery disease (CAD) have always been based on the detection of the presence and extent of ischaemia by physical or pharmacological stress tests with or without the aid of imaging methods (e.g. exercise stress, test, stress echocardiography, single-photon emission computed tomography, or stress cardiac magnetic resonance). These methods show high performance to assess obstructive CAD, whilst they do not show accurate power to detect non-obstructive CAD. The introduction into clinical practice of coronary computed tomography angiography, the only non-invasive method capable of analyzing the coronary anatomy, allowed to add a crucial piece in the puzzle of the assessment of patients with suspected or chronic IHD. The current review evaluates the technical aspects and clinical experience of coronary computed tomography in the evaluation of atherosclerotic burden with a special focus about the new emerging application such as functional relevance of CAD with fractional flow reserve computed tomography (CT)-derived (FFRct), stress CT perfusion, and imaging inflammatory makers discussing the strength and weakness of each approach.

Quantification of extracellular volume with cardiac computed tomography in patients with dilated cardiomyopathy.

BACKGROUND: Cardiac computed tomography (CCT) was recently validated to measure extracellular volume (ECV) in the setting of cardiac amyloidosis, showing good agreement with cardiovascular magnetic resonance (CMR). However, no evidence is available with a whole-heart single source, single energy CT scanner in the clinical context of newly diagnosed left ventricular dysfunction. Therefore, the aim of this study was to test the diagnostic accuracy of ECVCCT in patients with a recent diagnosis of dilated cardiomyopathy, having ECVCMR as the reference technique. METHODS: 39 consecutive patients with newly diagnosed dilated cardiomyopathy (LVEF <50%) scheduled for clinically indicated CMR were prospectively enrolled. Myocardial segment evaluability assessment with each technique, agreement between ECVCMR and ECVCCT, regression analysis, Bland-Altman analysis and interclass correlation coefficient (ICC) were performed. RESULTS: Mean age of enrolled patients was 62 â€‹± â€‹11 years, and mean LVEF at CMR was 35.4 â€‹± â€‹10.7%. Overall radiation exposure for ECV estimation was 2.1 â€‹± â€‹1.1 â€‹mSv. Out of 624 myocardial segments available for analysis, 624 (100%) segments were assessable by CCT while 608 (97.4%) were evaluable at CMR. ECVCCT demonstrated slightly lower values compared to ECVCMR (all segments, 31.8 â€‹± â€‹6.5% vs 33.9 â€‹± â€‹8.0%, p â€‹< â€‹0.001). At regression analysis, strong correlations were described (all segments, r â€‹= â€‹0.819, 95% CI: 0.791 to 0.844). On Bland-Altman analysis, bias between ECVCMR and ECVCCT for global analysis was 2.1 (95% CI: -6.8 to 11.1). ICC analysis showed both high intra-observer and inter-observer agreement for ECVCCT calculation (0.986, 95%CI: 0.983 to 0.988 and 0.966, 95%CI: 0.960 to 0.971, respectively). CONCLUSIONS: ECV estimation with a whole-heart single source, single energy CT scanner is feasible and accurate. Integration of ECV measurement in a comprehensive CCT evaluation of patients with newly diagnosed dilated cardiomyopathy can be performed with a small increase in overall radiation exposure.

The Role of Cardiac Magnetic Resonance in Aortic Stenosis and Regurgitation.

Cardiac magnetic resonance (CMR) imaging is a well-set diagnostic technique for assessment of valvular heart diseases and is gaining ground in current clinical practice. It provides high-quality images without the administration of ionizing radiation and occasionally without the need of contrast agents. It offers the unique possibility of a comprehensive stand-alone assessment of the heart including biventricular function, left ventricle remodeling, myocardial fibrosis, and associated valvulopathies. CMR is the recognized reference for the quantification of ventricular volumes, mass, and function. A particular strength is the ability to quantify flow, especially with new techniques which allow accurate measurement of stenosis and regurgitation. Furthermore, tissue mapping enables the visualization and quantification of structural changes in the myocardium. In this way, CMR has the potential to yield important prognostic information predicting those patients who will progress to surgery and impact outcomes. In this review, the fundamentals of CMR in assessment of aortic valve diseases (AVD) are described, together with its strengths and weaknesses. This state-of-the-art review provides an updated overview of CMR potentials in all AVD issues, including valve anatomy, flow quantification, ventricular volumes and function, and tissue characterization.

Left atrial appendage morphology at transesophageal echocardiography: how to improve reproducibility?

BACKGROUND: Left atrial appendage (LAA) morphology, investigated by computed tomography and magnetic resonance imaging, has proved to relate to the risk of cerebrovascular events in patients with atrial fibrillation (AF). The aim of the present study was to assess reproducibility of transesophageal echocardiography (TEE) imaging in describing LAA morphology. METHODS: Two-hundred consecutive patients referred for TEE were enrolled. In the first group of 47 (23.5%) patients LAA morphology was analyzed by conventional TEE and described as ChickenWing, Windsock, Cactus or Cauliflower. In the second group of 153 (76.5%) patients, instead, a 3D-Xplane diagnostic algorithm was performed to stratify LAA morphology as linear (ChickenWing) or complex (Windsock/Cactus and Cauliflower). Interobserver variability within three independent readers was assessed in both groups of patients and stratified by operator's experience and training. In a subgroup of 19 (12.4%) patients, the agreement of LAA morphology description by 3D-Xplane diagnostic algorithm was compared to cardiac magnetic resonance. RESULTS: By conventional TEE the agreement among operators on LAA morphology classification was poor (ρ<0.13). The 3D-XPlane diagnostic algorithm, significantly increased interobserver agreement up to ρ=0.32 within all readers and up to ρ=0.82 among the experienced and specifically trained operators. LAA morphology description in this latter group provided strong agreement with cardiac magnetic resonance (up to ρ=0.77). CONCLUSIONS: LAA morphology assessment is challenging by conventional TEE. To improve reproducibility, the use of the 3D-Xplane technique combined with a specific diagnostic algorithm and training of the operators is fundamental.

Subclinical Left Ventricular Dysfunction in Severe Obesity and Reverse Cardiac Remodeling after Bariatric Surgery.

AIM: Obesity is associated with an increased cardiovascular risk. This study aimed to assess the role of echocardiography in the early detection of subclinical cardiac abnormalities in a cohort of obese patients with a preserved ejection fraction (EF) undergoing bariatric surgery. METHODS AND RESULTS: Forty consecutive severely obese patients (body mass index≥35 kg/m2) referring to our center for bariatric surgery were enrolled in this prospective cohort study. Despite a baseline EF of 61% ± 3%, almost half patients (43%) had a systolic dysfunction (SD) defined as global longitudinal strain (GLS)>-18%, and most of them (60%) had left ventricular hypertrophy (LVH) or concentric remodeling (CR). At 10-months after surgery, body weight decreased from 120 ± 15 kg to 83 ± 12 kg, body mass index from 44 ± 5 kg/m2 to 31 ± 5 kg/m2 (both P < 0.001). Septal and left ventricular posterior wall thickness decreased respectively from 10 ± 1 mm to 9 ± 1 mm (P = 0.004) and from 10 ± 1 mm to 9 ± 1 mm (P = 0.007). All systolic parameters improved: EF from 61% ± 3% to 64% ± 3% (P = 0.002) and GLS from -17% ± 2% to -20% ± 1% (P < 0.001). Epicardial fat thickness reduction (from 4.7 ± 1 mm to 3.5 ± 0.7 mm, P < 0.001) correlated with the reduction of left atrial area (P < 0.001 R = 0.35) and volume (P = 0.02 R = 0.25). Following bariatric surgery, we observed a reduced prevalence of LVH/CR (before 60%, after 22%, P = 0.001) and a complete resolution of preclinical SD (before 43%, after 0%, P < 0.001). Moreover, a postoperative reduction of at least 30 kg correlated with regression of septal hypertrophy (P < 0.001). CONCLUSIONS: Obese patients candidate to bariatric surgery have an high prevalence of preclinical SD and LVH/CR, early detectable with echocardiography. Bariatric surgery is associated with reverse cardiac remodeling; it might also have a preventive effect on atrial fibrillation occurrence by reducing its substrate.

A pacemaker lead in the left ventricle: An "unexpected" finding?

Inadvertent malposition of a pacemaker lead in the left ventricle is uncommon, but it should not be misdiagnosed. We report the case of a 68-year-old woman with symptomatic sick-sinus syndrome requiring pacemaker implantation. Shortly afterwards the lead was extracted and a new pacemaker was contralaterally implanted due to pocket hematoma and suspected lead fracture. Three months later, she was referred to our echocardiography laboratory complaining of asthenia. At transthoracic echocardiography an echo-bright linear structure was recognized in left atrium, passing through the mitral valve and leaning against the posterior left ventricular wall. In short-axis and apical views, the lead apparently crossed the interatrial septum through patent foramen ovale. The QRS-paced electrocardiogram showed right bundle branch block morphology. The lead was apparently well positioned, examining the chest X-ray postero-anterior view. On the contrary, by latero-lateral view and left-anterior oblique view, lead curvature was consistent with misplacement into the left ventricle. Malposition was confirmed by transesophageal echocardiography. Given the relatively recent implant, system revision with lead extraction was scheduled and completed without complications. This case report is intended to improve our awareness in the prevention and in the prompt detection of misplaced pacemaker leads in order to manage an immediate correction. .

Left Atrial Function after Atrial Fibrillation Cryoablation Concomitant to Minimally Invasive Mitral Valve Repair: A Pilot Study on Long-Term Results and Clinical Implications.

Background and Objectives: Surgical atrial fibrillation (AF) ablation concomitant to minimally invasive mitral valve repair has been proven to offer improved short- and long-term sinus rhythm (SR) maintenance compared to mitral valve surgery only. The objective of the present study was to explore, by thorough echocardiographic assessment, long-term morphological and functional left atrial (LA) outcomes after this combined surgical procedure. Materials and Methods: From October 2006 to November 2015, 48 patients underwent minimally invasive mitral valve repair and concomitant surgical AF cryoablation. Results: After 3.8 ± 2.2 years, 30 (71.4%) of those completing the follow-up (n = 42, 87.5%) presented SR. During follow-up, four (9.5%) patients suffered from cerebrovascular accidents and two of these subjects had a long-standing persistent AF relapse and were in AF at the time of the event, while the other two were in SR. An echocardiographic study focused on LA characteristics was performed in 29 patients (69.0%). Atrial morphology and function (e.g., maximal LA volume indexed to body surface area and total LA emptying fraction derived from volumes) in patients with stable SR (60.6 ± 13.1 mL/mq and 25.1 ± 7.3%) were significantly better than in those with AF relapses (76.8 ± 16.2 mL/mq and 17.5 ± 7.4%; respectively, p = 0.008 and p = 0.015). At follow-up, patients who suffered from ischemic cerebral events had maximal LA volume indexed to body surface area 61 ± 17.8 mL/mq, with total LA emptying fraction derived from volumes 23.6 ± 13.7%; patients with strokes in SR showed very enlarged LA volume (>70 mL/mq). Conclusions: AF cryoablation concomitant with minimally invasive mitral valve repair provides a high rate of SR maintenance and this relates to improved long-term morphological and functional LA outcomes. Further prospective studies are needed to define the cut-off values determining an increase in the risk for thromboembolic complications in patients with restored stable SR.

Is trazodone more effective than clomipramine in major depressed outpatients? A single-blind study with intravenous and oral administration.

OBJECTIVE: Some antidepressants, such as trazodone or clomipramine, can be administered intravenously in patients with major depressive disorder (MDD), with potential benefits compared to the standard oral treatment, but available data about their efficacy are limited. The present study was aimed to compare the effectiveness of trazodone and clomipramine (intravenous [i.v.] followed by oral administration). METHODS: Some 42 patients with a diagnosis of MDD according to the DSM-5 were selected and treated with i.v. trazodone or clomipramine according to clinical judgment. The Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, and the Montgomery-Åsberg Depression Rating Scale were administered at baseline, after 2 weeks, and after 6 weeks, as well as after 1 week of intravenous antidepressant administration. Raters were blinded to type of treatment. RESULTS: No significant differences were found between treatment groups in terms of effectiveness at endpoint. Borderline statistical significance was found in terms of number of responders in favor of trazodone. In addition, patients treated with trazodone reported fewer total side effects than those treated with clomipramine. CONCLUSION: Both i.v. trazodone and clomipramine are rapid and effective options for improving depressive symptoms, although trazodone appears to be tolerated better. Further studies with larger samples and double-blind conditions are warranted to confirm our results.

Efficacy of oral trazodone slow release following intravenous administration in depressed patients: a naturalistic study.

BACKGROUNDS: Up to date, no studies in literature assessed the efficacy of a treatment schedule including i.v. trazodone followed by its oral administration. In light of this lack of evidence, the aim of the present study was to evaluate the efficacy and tolerability of trazodone, administered first i.v. and then orally in a sample of Major Depressive Disorder (MDD) patients. METHODS: Thirty four patients underwent i.v. administration of trazodone (75-100 mg in 250 mL of saline) for 1 week. During the second week, oral extended-release formulation (150-300 mg per day) was added to the i.v. administration. Finally, extended-release trazodone was orally administration at doses of 150-300 mg per day. Psychometric scales were performed at baseline (T0), after 2 weeks (T1), 6 weeks (T2), after 3 months (T3), and 6 months (T4). RESULTS: The total sample included 34 subjects (14 males and 20 females). There was a statistically significant decrease in Hamilton Depression Rating Scale total scores from T0 to T1 (t=9.06; df=33), from T1 to T2 (t=4.96; df=29), from T2 to T3 (t=4.08; df=19), and from T3 to T4 (t=2.25; df=19); in Hamilton Anxiety Rating Scale total scores from T0 to T1 (t=8.79; df=33) and from T1 to T2 (t=5.61; df=29); in Montgomery-Asberg Depression Rating Scale total scores from T0 to T1 (t=9.30; df=33), from T1 to T2 (t=5.69; df=29), and from T2 to T3 (t=3.16; df=19). CONCLUSIONS: This finding confirms previous results on depression with concomitant anxiety symptoms: focusing on trazodone prolonged-release formulation, available data documented its efficacy in MDD.

THE USE OF LONG-ACTING ANTIPSYCHOTICS FOR THE MANAGEMENT OF AGGRESSIVENESS IN SCHIZOPHRENIA: A CLINICAL OVERVIEW.

Aggressive behaviour represents a challenge in the treatment of patients with schizophrenia, being often associated with clinical predictors of severity of illness such as poor insight, psychotic re-exacerbation, concomitant substance misuse or comorbidity with personality disorders. As psychotic relapses and consequent risk of aggressive behaviour are often associated with a poor compliance, purpose of the present manuscript is to give an overview of the available data about the use of depot antipsychotics for the management of violence in patients with schizophrenia. A research in the main database sources has been conducted to identify relevant papers about the topic. Few studies (most of them retrospective and with small sample sizes) have investigated the effectiveness of depot antipsychotic for the treatment of aggressive behaviour in schizophrenia. Aripiprazole depot appears to be promising for the management of aggressive behaviour of subjects with schizophrenia, however data about its efficacy in the long-term are absent and lack of evidence prevents the recommendation of this compound for the treatment of aggressiveness in subjects affected by schizophrenia. In addition, there is not sufficient evidence to conclude that a specific depot antipsychotic may have a better efficacy on aggressive behaviour of patients affected by schizophrenia. Prospective comparative studies (e.g. with oral clozapine and aripiprazole depot) are needed to assess the real clinical advantage of the use of depot antipsychotic versus oral alternatives for the prevention of violent behaviour in schizophrenia.

Intraindividual and Interindividual Variability of Olanzapine Trough Concentrations in Patients Treated With the Long-Acting Injectable Formulation.

BACKGROUND: A long-acting injectable (LAI) formulation of olanzapine has been developed as an alternative to oral regimens. A therapeutic range of 20 to 80 ng/mL for oral olanzapine trough concentrations has been proposed. Here, we sought to investigate the intraindividual and interindividual variability of olanzapine concentrations with time in patients on maintenance therapy with the LAI formulation carried out in the routine clinical practice. METHODS: To address this issue, we carried out a retrospective analysis of therapeutic drug monitoring of olanzapine concentrations in 21 schizophrenic patients on maintenance LAI olanzapine. Drug concentrations were correlated with LAI olanzapine doses, duration of treatment, and main clinical characteristics. RESULTS: Fifty percent of the patients had olanzapine trough concentrations lower than 20 ng/mL. Only drug doses significantly correlated with olanzapine exposure. Mean interindividual and intraindividual coefficients of variations of olanzapine concentrations were 56% (range, 21%-97%) and 34% (range, 15%-69%), respectively. CONCLUSIONS: We have documented that, in a real-life setting, a large proportion of patients treated with olanzapine LAI had drug trough concentrations of less than 20 ng/mL; wide intraindividual and interindividual variability of olanzapine concentrations has been also observed. Our results could provide the rationale for the design of larger prospective, concentration-controlled clinical trials specifically designed with the goal to identify ad hoc therapeutic ranges of drug concentrations for olanzapine LAI.

Clinical outcomes of overlapping versus non-overlapping everolimus-eluting absorb bioresorbable vascular scaffolds: An analysis from the multicentre prospective RAI registry (ClinicalTrials.gov identifier: NCT02298413).

OBJECTIVES: To compare clinical outcomes of patients treated with overlapping versus non-overlapping Absorb BVS. BACKGROUND: Limited data are available on the clinical impact of stent overlap with the Absorb BVS bioresorbable stent. METHODS: We compared outcomes of patients receiving overlapping or non-overlapping Absorb BVS in the multicenter prospective RAI Registry. RESULTS: Out of 1,505 consecutive patients treated with Absorb BVS, 1,384 were eligible for this analysis. Of these, 377 (27%) were in the overlap group, and 1,007 (73%) in the non-overlap group. The most frequent overlap configuration was the marker-to-marker type (48%), followed by marker-over-marker (46%) and marker-inside-marker (6%) types. Patients of the overlap group had higher prevalence of multivessel disease and higher SYNTAX score, and required more frequently the use of intravascular imaging. At a median follow-up of 368 days, no difference was observed between overlap and non-overlap groups in terms of a device-related composite endpoint (cardiac death, TV-MI, ID-TLR) (5.8% vs. 4.1%, P = 0.20) or of a patient-related composite endpoint (any death, any MI, any revascularization) (15.4% vs. 12.5%, P = 0.18). Cardiac death (1.0% vs. 1.3%, P = 0.54), MI (4.5% vs. 3.6%, P = 0.51), TVR (4.5% vs. 3.6%, P = 0.51) and stent thrombosis (1.1 vs. 1.5%, P = 1.00) were also comparable between groups. When assessing outcomes of the overlap population according to overlap configurations used, no difference was observed in terms of the device- or patient-related composite endpoints. CONCLUSIONS: Outcomes of patients with or without overlapping BVS were comparable at mid-term follow-up despite higher angiographic complexity of the overlap subset. © 2017 Wiley Periodicals, Inc.

Effect of N-Desalkylquetiapine/Quetiapine Plasma Level Ratio on Anxiety and Depression in Bipolar Disorder: A Prospective Observational Study.

BACKGROUND: The aim of this study was to analyze the relationships between quetiapine and N-desalkylquetiapine plasma levels and clinical improvement, particularly, in regard to depressive and anxious symptoms and to hostility. METHODS: This was a prospective observational study that involved 37 outpatients diagnosed as having bipolar disorder I or II. All the patients were observed during a clinical acute and postacute phase. Patients were prescribed 50-800 mg of quetiapine. Patients were evaluated at baseline, after 15 days and after 3 months using the Brief Psychiatry Rating Scale with particular reference to the dimensions of depression, anxiety, and hostility. The plasma concentrations of quetiapine and N-desalkylquetiapine were determined after 3 months using blood samples taken at steady state. RESULTS: There was a significant relationship between the N-desalkylquetiapine/quetiapine ratio and the improvement in the depression dimension, and there was not a significant relationship between the N-desalkylquetiapine/quetiapine ratio and anxiety and hostility improvement. Quetiapine treatment was well tolerated, and there were no extrapyramidal, anticholinergic, or other side effects to note. There was no relationship between plasma quetiapine or N-desalkylquetiapine concentrations and side effects. CONCLUSIONS: Our findings confirm the efficacy of quetiapine on depressive symptoms, and the available data support that quetiapine's antidepressant activity is mediated by the active metabolite norquetiapine, and it exemplifies the case of an active metabolite that can make a drug like quetiapine originally introduced as an antipsychotic a useful antidepressant agent.