Quantitative assay of capreomycin oleate levels in a drug formulation for inhalation with a fully validated HPLC method

Capreomycin sulfate (CS), a mixture of 4 closely related compounds (powder mainly comprised of 2 forms), commonly injected intramuscularly is intended to be administer by inhalation for the treatment of pulmonary tuberculosis.In order to increase the drug residence time in the lung, capreomycin hydrophobicity was enhanced by substituting sulfate with oleate, thus obtaining capreomycin oleate (CO). The generation of a more hydrophobic ion-pair allows the reduction of the drug solubilisation in the bronchoalveolar fluids as well as its systemic absorption.The aim of the present study was to quantify CO in an in-house prepared drug formulation for inhalation. In this regard, a Hydrophilic Liquid Interaction Chromatography (HILIC) method was optimized with acetonitrile (ACN)/water containing eluents and a diol-type stationary phase. The optimal eluent composition [ACN/water-80/20 (v/v), 20 mM ammonium formate, 3.0 wspH] produced a good separation (α equal to 1.15) between the two main peaks. The developed HILIC method succeeded in the quantitative assay of CO in the drug formulation and was fully validated. Very good precision and accuracy in the short- and long-period along with appreciably low LOD and LOQ values (respectively 1.75 and 5.25 μg/mL) turned out.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

2D/3D echocardiographic determinants of left ventricular reverse remodelling after mitraclip implantation

AIMS: The aim of this study was to describe incidence and determinants of left ventricular reverse remodelling (r-LVR) at 6 months follow-up after MitraClip implantation in patients with secondary severe mitral regurgitation (MR) and reduced left ventricular ejection fraction (LVEF). METHODS AND RESULTS: Forty-five patients, undergoing MitralClip implantation with low ejection fraction and high surgical risk were enrolled in this study. Three of them died before the scheduled 6 months follow-up period and one patient had cardiac surgery due to MitraClip detachment. All patients underwent transthoracic 2D and 3D echocardiography before and 6 months after the procedure. A significant MR severity reduction and an improvement in New York Heart Association (NYHA) class were detected in all patients. The study population was divided in two groups according to the presence of r-LVR (51%, n = 23 patients) or not (non-rLVR group, 18 patients). Non-significant differences in MR aetiology and number of clips implanted were found. Left ventricular reverse remodelling patients showed significant lower values of logistic EuroSCORE and STS score, left ventricular end-diastolic volume index (LVEDV/i), right ventricular end systolic area, and pulmonary artery systolic pressure (PASp) at baseline evaluation. At multivariable analysis, baseline PASp value resulted to be the only independent predictor of r-LVR [odds ratio 95% confidence interval 0.94 (0.89-0.99), P = 0.021]. In r-LVR patients, a significant improvement in LVEF and global longitudinal strain and a reduction in left atrial volume index were detected after 6 months, whereas in non-rLVR subgroup a significant increase in both LVEDV/i and left ventricular end-systolic volume index was observed at follow-up. CONCLUSION: Even if a reduction of MR was detected in all patients after MitralClip implant, our findings suggest that end-stage patients presenting with higher left ventricular volumes, logistic scores, and PASp may not benefit from the procedure at longer follow-up in terms of left ventricular function

Mid-term repair durability after MitraClip implantation in patients with functional mitral regurgitation

BACKGROUND: The aim of this study was to identify variables that are associated with the durability of percutaneous repair of secondary mitral regurgitation at 6-month follow-up. METHODS AND RESULTS: Thirty-five consecutive patients with functional mitral regurgitation scheduled for MitraClip implant were enrolled. Left ventricular (LV) volumes and function and mitral valve characteristics were assessed before and immediately after MitraClip implantation using three-dimensional transesophageal echocardiography. Five patients with an unsuccessful procedure were excluded. The other patients were subdivided according to repair durability: group 1 with a durable repair (19 patients, 65%) and group 2 with significant mitral regurgitation recurrence (11 patients, 35%). At baseline, group 1 patients had smaller and more elliptical mitral valve annulus (1055 ± 241 vs. 1273 ± 359 mm, P = 0.02 and 125 ± 11 vs. 117 ± 16%, P = 0.02), a smaller left atrial volume (54.1 ± 26 vs. 71.5 ± 20 ml, P = 0.005) and lower systolic pulmonary artery pressure (38 ± 11 vs. 49 ± 12 mmHg, P = 0.03). Baseline LV end systolic volume had a linear correlation with the 3D annulus area (P = 0.048) and an inverse correlation with annulus ellipticity (P = 0.021). Group 1 patients showed an increase in annulus ellipticity after MitraClip (125 ± 17 vs. 141 ± 23%, P = 0.014). CONCLUSION: Percutaneous mitral valve repair leads to a significant and stable mitral regurgitation reduction in a large number of patients. Annulus dimensions and remodeling as well as left atrial area and pulmonary hypertension seem to be associated with durability of the procedure

3D Echo Characterization of Proportionate and Disproportionate Functional Mitral Regurgitation before and after Percutaneous Mitral Valve Repair

Background: The impact of percutaneous mitral valve repair (PMVr) on long-term prognosis in patients with functional mitral regurgitation (FMR) is still unclear. Recently, a new conceptual framework classifying FMR as proportionate (P-MR) and disproportionate (D-MR) was proposed, according to the effective regurgitant orifice area/left ventricular end-diastolic volume (EROA/LVEDV) ratio. The aim was to assess its possible influence on PMVr efficacy. Methods: A total of 56 patients were enrolled. MV annulus, LV volumes and function were assessed. Global longitudinal strain (GLS) was also calculated. Patients were divided into two groups, according to the EROA/LVEDV ratio. Echocardiographic follow-up was performed after 6 months, and adverse events were collected after 12 months. Results: D-MR patients (n = 28, 50%) had a significantly more elliptical MV annulus (p = 0.048), lower tenting volume (p = 0.01), higher LV ejection fraction (LVEF: 32 ± 7 vs. 26 ± 5%, p = 0.003), lower LVEDV, LV end-systolic volume (LVESV) and mass (LVEDV/i: 80 ± 20 vs. 126 ± 27 mL, p = 0.001; LVESV/i: 60 ± 20 vs. 94 ± 23 mL, p < 0.001; LV mass: 249 ± 63 vs. 301 ± 69 gr, p = 0.035). GLS was more impaired in P-MR (p = 0.048). After 6 months, P-MR patients showed a higher rate of MR recurrence. After 12 months, the rate of CV death and rehospitalization due to HF was significantly higher in P-MR patients (46% vs. 7%, p < 0.001). P-MR status was strongly associated with CV death/rehospitalization (HR = 3.4, CI 95% = 1.3–8.6, p = 0.009). Conclusions: Patients with P-MR seem to have worse outcomes after PVMr than D-MR patients. Our study confirms the importance of the EROA/LVEDV ratio in defining different subsets of FMR based on the anatomical characteristic of MV and LV

Prognostic role of pre- and post-interventional myocardial injury in patients undergoing transcatheter aortic valve implantation

Chronic pre-procedural and acute post-procedural myocardial injury are frequently observed in patients with aortic stenosis undergoing trans-catheter aortic valve implantation (TAVI). The aim of our study was to investigate the prognostic role of high sensitivity cardiac troponins (hs-cTns) elevation before and after TAVI

Is intravascular ultrasound beneficial for percutaneous coronary intervention of bifurcation lesions? Evidence from a 4,314-patient registry

Coronary bifurcations remain a challenging lesion subset for percutaneous coronary intervention (PCI). It is unclear whether intravascular ultrasound (IVUS) guidance can improve PCI results in bifurcations. We aimed to compare IVUS-guided PCI versus standard PCI in a large registry of patients undergoing PCI for bifurcations in the drug-eluting stent era

Impact of Complete Revascularization on Development of Heart Failure in Patients With Acute Coronary Syndrome and Multivessel Disease: A Subanalysis of the CORALYS Registry

Background The impact of complete revascularization (CR) on the development of heart failure (HF) in patients with acute coronary syndrome and multivessel coronary artery disease undergoing percutaneous coronary intervention remains to be elucidated. Methods and Results Consecutive patients with acute coronary syndrome with multivessel coronary artery disease from the CORALYS (Incidence and Predictors of Heart Failure After Acute Coronary Syndrome) registry were included. Incidence of first hospitalization for HF or cardiovascular death was the primary end point. Patients were stratified according to completeness of coronary revascularization. Of 14 699 patients in the CORALYS registry, 5054 presented with multivessel disease. One thousand four hundred seventy‐three (29.2%) underwent CR, while 3581 (70.8%) did not. Over 5 years follow‐up, CR was associated with a reduced incidence of the primary end point (adjusted hazard ratio [HR], 0.66 [95% CI, 0.51–0.85]), first HF hospitalization (adjusted HR, 0.67 [95% CI, 0.49–0.90]) along with all‐cause death and cardiovascular death alone (adjusted HR, 0.74 [95% CI, 0.56–0.97] and HR, 0.56 [95% CI, 0.38–0.84], respectively). The results were consistent in the propensity‐score matching population and in inverse probability treatment weighting analysis. The benefit of CR was consistent across acute coronary syndrome presentations (HR, 0.59 [95% CI, 0.39–0.89] for ST‐segment elevation myocardial infarction and HR, 0.71 [95% CI, 0.50–0.99] for non‐ST‐elevation acute coronary syndrome) and in patients with left ventricular ejection fraction >40% (HR, 0.52 [95% CI, 0.37–0.72]), while no benefit was observed in patients with left ventricular ejection fraction ≤40% (HR, 0.77 [95% CI, 0.37–1.10], P for interaction 0.04). Conclusions CR after acute coronary syndrome reduced the risk of first hospitalization for HF and cardiovascular death, as well as first HF hospitalization, and cardiovascular and overall death both in patients with ST‐segment elevation myocardial infarction and non‐ST‐elevation acute coronary syndrome. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT 04895176