Effectiveness and Tolerability of Supratherapeutic Dosing of Vortioxetine in Patients With Treatment-Resistant Depression.

Objective: To evaluate the effectiveness and tolerability of vortioxetine at supratherapeutic dosages in patients with treatment-resistant depression.Methods: A retrospective observational naturalistic study was conducted in 56 depressed patients resistant to standard care treatment from September 2020 to April 2021. Effectiveness of the vortioxetine treatments was evaluated through Clinical Global Impressions (CGI) score, comparing CGI values at the beginning (T0) of the vortioxetine treatment with CGI values at the earliest of these 2 time points (T1): (1) 8 weeks of treatment with supratherapeutic dosages and (2) day of vortioxetine discontinuation or daily dosage reduction to ≤ 20 mg due to side effects. The tolerability and safe of vortioxetine were also monitored.Results: Fifty-six patients (32 females and 24 males, mean ± SD age of 51.1 ± 9.3 years) were included in the study. Thirty-seven patients received vortioxetine 30 mg/d, while 19 patients were treated with a 40-mg/d dosage. CGI scores significantly decreased (P < .001) in patients treated with 30 mg/d and 40 mg/d, respectively. No severe side effects were reported. Weight gain and nausea were the most common reported side effects. Nausea and limited efficacy were recorded as the most frequent reasons for vortioxetine dose reduction. None of the patients required vortioxetine discontinuation.Conclusions: Supratherapeutic doses of vortioxetine were relatively well-tolerated and effective in patients with treatment-resistant depression.

[Prevalence of cardiac and extracardiac incidental findings in the evaluation of coronary artery disease by multidetector computed tomography]. / Prevalenza di reperti occasionali cardiaci ed extracardiaci nella valutazione delle coronarie con tomografia computerizzata multidetettore.

BACKGROUND: With the widespread use of multidetector computed tomography (MDCT) coronary angiography, cardiac and extracardiac incidental findings in cardiac imaging might be detected. The aim of this study was to determine the prevalence of cardiac and extracardiac incidental findings in a population of consecutive patients undergoing coronary MDCT. METHODS: A total of 840 consecutive patients with known or suspected heart disease underwent cardiac MDCT. All patients were assessed with 64-slice MDCT; the examination was performed by limiting the anatomical region examined between the bifurcation of the trachea and the cardiac apex with the aim of obtaining excellent image quality and low cardiac radiological exposure. RESULTS: Overall, 81 incidental findings in 72 patients (9%) were identified, of which 18 were cardiac (2%) and 63 extracardiac (7%). Extracardiac incidental findings were mainly represented by pulmonary nodules (19%). CONCLUSIONS: A significant number of cardiac and extracardiac incidental findings were observed at cardiac MDCT, with the prevalence depending on technical aspects of image acquisition and patient characteristics. Incidental findings should be carefully searched for and reported because they may have an impact on clinical follow-up indications that is not without cost and risk.

Left ventricular rotation and twist assessed by four-dimensional speckle tracking echocardiography in healthy subjects and pathological remodeling: a single center experience.

BACKGROUND: Left ventricular (LV) twist represents a main aspect of ejection. It is defined as the difference between the apical and basal rotation and can be assessed by speckle tracking echocardiography (STE). Twist may be underestimated when assessed by two-dimensional-echocardiography due to the difficulty of identifying the real apex. Aim of this study was to evaluate the LV twist by means of three-dimensional (3D)-STE and verify if the inclusion of the apex can modify the assessment of the global twist. METHODS: LV volume acquisition with a fully sampled matrix array transducer was performed in 30 healthy subjects and 79 patients with cardiomyopathy secondary to different etiologies. Thirty-nine patients had a LV ejection fraction (EF) ≥50% (Group A), 16 showed an EF between 40 and 50% (Group B), and 24 patients had an EF ≤40%(Group C). LV rotation was assessed by 3D-STE at basal, medium, apical, and apical-cap levels. Twist was computed considering the apex either at the apical level (Twist(Api) ) or at the apical-cap level (Twist(AC) ). RESULTS: LV rotation resulted to be progressively higher from base to apical-cap (P < 0.0001) with a significant difference between the apex and the apical-cap level (6.20 ± 3.90° vs. 10.23 ± 7.52°; P < 0.001). Such a difference was constantly found in all Groups (P < 0.01 for Group A, P < 0.05 for Group B and C). Twist(Api) was also significantly lower than Twist(AC) both in the overall population (6.2 ± 3.89° vs. 10.23 ± 7.51°; P < 0.001) and in the different subgroups ( CONTROLS: 9.61 ± 3.39° vs. 13.75 ± 6.51°; Group A: 10.49 ± 4.77° vs. 16.37 ± 8.49°; Group B: 6.67 ± 3.44° vs. 9.14 ± 5.55°; Group C: 33 ± 2.62° vs. 5.26 ± 3.74°; P < 0.05 for all the comparisons). CONCLUSIONS: Identification and inclusion of apical-cap is relevant for twist assessment and can be carried out efficiently by 3D-STE. The inclusion of the true apex in the calculation significantly affects the analysis of twist both in normal individuals and patients with different myocardial diseases.

Evaluation of Brugada syndrome by cardiac magnetic resonance.

Brugada syndrome (BrS) has been originally considered to occur in structural normal hearts. However recent pathological and imaging data suggest that structural and functional changes may be present in this syndrome. This study was designed to elucidate whether any macroscopic heart abnormality is detectable in patients with BrS. For this purpose we used cardiac magnetic resonance (CMR). Twenty-nine patients displaying the BrS type-1 ECG pattern and 29 healthy controls underwent CMR (1.5 Tesla). Left (LV) and right ventricular (RV) dimensions, function and regional contractility were evaluated. Late-gadolinium-enhancement (LGE) imaging was obtained in 24 patients. We found no difference between BrS patients and controls regarding LV and RV dimensions and ejection fraction. RV wall motion abnormalities (WMA) were detected in 19 patients (65.5%) and in 22 control subjects (75.9%). The majority of these WMA were attributable to areas of hypokinesia and found in the RV inferior wall. None of the patients showed LGE. No differences were detected between controls and the different subgroups of BrS patients according to symptoms, family history and spontaneous type-1 ECG pattern. BrS patients do not differ from normal subjects with regard to dimensions and global function of both LV and RV. BrS patients may show RV-WMA, however similar changes are also present in healthy subjects and may therefore represent a physiological behaviour of RV. The lack of LGE further confirms the absence of myocardial structural damage. Our results indicate that BrS seems to occur in individuals with structurally and functionally normal heart.

Three-dimensional simultaneous strain-volume analysis describes left ventricular remodelling and its progression: a pilot study.

AIMS: Three-dimensional (3D)-echocardiography speckle imaging allows the evaluation of frame-by-frame strain and volume changes simultaneously. The aim of the present investigation was to describe the strain-volume combined assessment in different patterns of cardiac remodelling. METHODS AND RESULTS: Fifty patients received a 3D acquisition. Patients were classified as follows: healthy subjects (CNT), previous AMI, and normal ejection fraction (EF; group A); ischaemic cardiomyopathy with reduced EF (group B); hypertrophic/infiltrative cardiomyopathy (group C). Values of 3D strain were plotted vs. volume for each frame to build a strain-volume curve for each case. Peak of radial, longitudinal, and circumferential systolic strain (Rεp, Lεp, and Cεp, respectively), slopes of the curves (RεSl, LεSl, CεSl), and strain to end-diastolic volume (EDV) ratio (Rε/V, Lε/V, Cε/V) were computed for the analysis. Strain-volume curves of the CNT group were steep and clustered, whereas, due to progressive dilatation and reduction of strains, progressive flattening could be demonstrated in groups A and B. Quantitative data supported visual assessment with progressive lower slopes (P< 0.05 for RεSl, CεSl, P= 0.06 for LεSl) and significantly lower ratios (P< 0.01 for Rε/V, Lε/V, and Cε/V). Group C showed an opposite behaviour with slopes and ratios close to those of normal subjects. Correlation coefficients between EDV and slopes of the curves were significant for all the directions of strain (CεSl: r = 0.891; RєSl: r = 0.704; LєSl: r = 0.833; P< 0.0001 for all). CONCLUSION: We measured left ventricular volumes and strain by 3D-echo and obtained strain-volume curve to evaluate their behaviour in remodelling. A distinctive and progressive pattern consistent with pathophysiology was observed. The analysis here shown could represent a new non-invasive method to assess myocardial mechanics and its relationship with volumes.

Does preoperative tethering symmetry affect left ventricular reverse remodeling after restrictive annuloplasty?

BACKGROUND: We hypothesized that a preoperative symmetric pattern with anterior mitral leaflet (AML) tethering predominance is related to lack of LVRR after restrictive annuloplasty. METHODS: In 300 patients with surgical annuloplasty for chronic ischemic mitral regurgitation the AML and posterior mitral leaflet (PML) tethering angles were quantified and patients were divided on the basis of the preoperative anterior/posterior tethering angle ratio: there were 144 patients with symmetric (Group 1) and 156 with asymmetric (Group 2) preoperative tethering pattern patients underwent echocardiography preoperatively, at discharge and at follow-up appointments (6 months [IQR 5-8 months]; late, 48 months [15-63 months]). Reverse remodeling was defined as a reduction in left ventricular end systolic volume index >15%. RESULTS: LVRR was higher in the asymmetric group at discharge (69.2% vs. 9.7%, p<0.001), early (70.55% vs. 10.45%, p<0.001 and late follow up (81.4% vs. 4.8%, p<0.001). At multivariable regression analysis corrected by significant key factors of LVRR, symmetric leaflet tethering (OR, 4.8 [95% CI 2.9-5.6], p<0.001), anterior tethering angle alpha'<39.5 degrees (OR, 5.0 [95% CI 2.0-6.6], p<0.001), coaptation height<11 mm (OR, 2.5 [95% CI 1.1-3.3], p=0.006) and coaptation length > or =8 mm at the end of procedure (OR, 2.0 [CI 0.8-3.0], p=0.01) were independent predictors of LVRR. Compared with patients with asymmetric pattern (adjusted OR 0.2 [95% CI 0.03-1.6), those with symmetric pattern had >4-fold odds for lack of LVRR. CONCLUSIONS: The preoperative symmetric pattern with AML prevalence was strongly associated with lack of reverse remodeling after annuloplasty. An accurate echocardiographic evaluation of the tethering mechanisms should be incorporated into clinical risk assessment and prediction models.

Insights on left ventricular and valvular mechanisms of recurrent ischemic mitral regurgitation after restrictive annuloplasty and coronary artery bypass grafting.

BACKGROUND: We investigated leaflet and subvalvular configurations to identify mechanisms leading to recurrent mitral regurgitation after combined undersized mitral annuloplasty and coronary artery bypass and to preoperatively recognize patients who are unlikely to benefit from this approach. METHODS: Among 261 subjects with chronic ischemic mitral regurgitation undergoing undersized annuloplasty and coronary bypass surgery at one institution between September 2001 and September 2007, 31 were excluded: 4 had intraoperative annuloplasty failure, 12 showed residual regurgitation, and 15 had incomplete echocardiograms available. The study population consisted of 230 patients who were divided into 2 groups: patients without (group 1, n = 176) or with (group 2, n = 54) late recurrent mitral regurgitation. Fifty healthy subjects were used as control subjects. Serial echocardiographic analysis was performed preoperatively, at discharge, and at follow-up appointments (early: median, 6 months [interquartile range, 5-6 months; late: median, 33 months [interquartile range, 17-51 months]). RESULTS: Subjects with late regurgitation had preoperatively more symmetric tethering (P < .001), more accentuated anterior mitral leaflet tethering (P < .001), and more restricted anterior leaflet excursion (P = .003) than patients in group 1. Postoperatively, tethering of the posterior leaflet increased (P < .001) and was predominant in both groups, whereas tethering of the anterior leaflet was reduced at discharge (P = .01 and P = .03, respectively), remaining constant afterward. Multivariable analysis showed an anterior tethering angle of 39.5 degrees or greater (P < .001), an anterior/posterior tethering angle ratio of 0.76 or greater (P < .001), an anterior leaflet excursion angle of 35 degrees or less (P = .001), and a coaptation height of 11 mm or greater (P = .04) to be predictors of recurrent mitral regurgitation. CONCLUSIONS: Preoperative symmetric tethering with anterior mitral leaflet predominance was strongly associated with recurrence of mitral regurgitation. Measures of leaflet tethering resulted in fundamental findings to identify ischemic patients who can really benefit from restrictive annuloplasty. Further larger studies are necessary to confirm our results.