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Congestion is the main therapeutic target of acute heart failure (HF) treatment, and loop diuretics (LDs) are widely used drugs for this purpose. Despite their extensive use, these agents remain largely understudied in terms of modality administration, treatment duration, and escalation dose for subjects responding poorly to therapy. LDs were initially investigated in several edematous statuses such as cirrhosis, nephrotic syndrome, and congestive HF and initially approved for the treatment of cardiogenic congestion in 1966. Despite the long history and the undoubted role in congestion management, the use of LDs in the acute phase is mostly based on the physician's experience, the oral amount chronically administered, and clinical decongestion response. Recent literature suggests monitoring diuretic activity by the evaluation of daily diuresis, weight loss, and sample urinary sodium assessment after early intravenous LD administration. More recently, the measurement of urinary sodium integrated with urinary and blood creatinine values and fluid status has been suggested as optimal marker to predict whole diuretic efficiency and to target the optimal dose. However, this method is not easily available in the chronic setting or in patients with recurrent hospitalization taking a high loop diuretic amount. Since high loop diuretic dose is related to diuretic resistance (DR) and poorer outcome, additional diuretics acting in different nephron sites are often required. Current sequential nephron blockade can stimulate diuresis by synergic mechanisms. This strategy is attempted in patients with poor response, revealing good results in the early period, but the effects of neuro-endocrine stimulation and electrolyte balance across long-term follow-up are still questioned. This paper reviews the historical course of loop diuretics and highlights the need for a universal approach based on clinical conditions, cardio–renal interactions, and HF phenotypes. [ABSTRACT FROM AUTHOR]

Background: SGLT2 inhibitors have been shown to reduce hospitalisation in patients with chronic heart failure (CHF). The cardioprotective mechanisms of gliflozins however have not been fully elucidated. The aim of this study was therefore to evaluate the effect of SGLT2 inhibitors on right and left ventricular function in patients with diabetes and HF. Methods: Seventy‐eight patients with diabetes and CHF were enroled in the study and followed up; 38 started treatment with SGLT2i, while the remaining 40 continued their previous antidiabetic therapy. All patients underwent conventional, TDI and strain echocardiography in an ambulatory setting, at the beginning and after 3 months of therapy with SGLT2i. Results: After 3 months of therapy with SGLT2i, echocardiographic parameters assessing both left and right ventricular dimensions and function were found as significantly improved in patients switching to SGLT2i than control group: LVEF (45 ± 9% vs. 40 ± 8%, p < 0.001), LVEDD (54 ± 6.5 vs. 56 ± 6.5 mm, p < 0.01), GLS (−13 ± 4% vs. −10 ± 3%, p < 0.001), TAPSE (21 ± 3 vs. 19 ± 3 mm, p < 0.001), RV S' (12.9 ± 2.5 vs 11.0 ± 1.9 cm/sec, p < 0.001) and PAsP (24 ± 8 vs. 31 ± 9 mmHg, p < 0.001). Also mitral (1.0 ± 0.5 vs. 1.3 ± 0.5, p < 0.01) and tricuspid regurgitation (1.0 ± 0.5 vs. 1.3 ± 0.5, p < 0.01) improved after SGLT2i therapy. Changes were not statistically significant in patients not treated with SGLT2i (p n.s. in all cases). Conclusions: In a real‐world scenario, treatment with SGLT2i in patients with CHF and diabetes is associated with an improvement in both left and right ventricular function assessed at echocardiography. These data may explain potential anti‐remodelling effects of gliflozins. [ABSTRACT FROM AUTHOR]

Aims: Sodium‐glucose cotransporter type 2 inhibitors (SGLT‐2i) represent a unique class of anti‐hyperglycaemic agents for type 2 diabetes mellitus that selectively inhibit renal glucose reabsorption, thereby increasing urinary excretion of glucose. Several studies have demonstrated the cardioprotective effects of SGLT‐2i in patients with heart failure (HF), unrelated to its glucosuric effect. It is unclear whether the benefits of SGLT‐2i therapy also rely on the improvement of left ventricular (LV) and/or right ventricular (RV) function in patients with HF. This study aimed to evaluate the effect of SGLT‐2i on LV and RV function through conventional and advanced echocardiographic parameters with a special focus on RV function in patients with HF. Methods and results: The Biventricular Evaluation of Gliflozins effects In chroNic Heart Failure (BEGIN‐HF) study is an international multicentre, prospective study that will evaluate the effect of SGLT‐2i on echocardiographic parameters of myocardial function in patients with chronic stable HF across the left ventricular ejection fraction (LVEF) spectrum. Patients with New York Heart Association Class II/III symptoms, estimated glomerular filtration rate > 25 mL/min/1.73 m2, age > 18 years, and those who were not previously treated with SGLT‐2i will be included. All patients will undergo conventional, tissue‐derived imaging (TDI), and strain echocardiography in an ambulatory setting, at time of enrolment and after 6 months of SGLT‐2i therapy. The primary endpoint is the change in LV function as assessed by conventional, TDI, and myocardial deformation speckle tracking parameters. Secondary outcomes include changes in RV and left atrial function as assessed by conventional and deformation speckle tracking echocardiography. Univariate and multivariate analyses will be performed to identify predictors associated with primary and secondary endpoints. Conclusions: The BEGIN‐HF will determine whether SGLT‐2i therapy improves LV and/or RV function by conventional and advanced echocardiography in patients with HF irrespective of LVEF. [ABSTRACT FROM AUTHOR]

Aims: Sacubitril/valsartan has changed the treatment of heart failure with reduced ejection fraction (HFrEF), due to the positive effects on morbidity and mortality, partly mediated by left ventricular (LV) reverse remodelling (LVRR). The aim of this multicenter study was to identify echocardiographic predictors of LVRR after sacubitril/valsartan administration. Methods and results: Patients with HFrEF requiring therapy with sacubitril/valsartan from 13 Italian centres were included. Echocardiographic parameters including LV global longitudinal strain (GLS) and global peak atrial longitudinal strain by speckle tracking echocardiography were measured to find the predictors of LVRR [= LV end‐systolic volume reduction ≥10% and ejection fraction (LVEF) improvement ≥10% at follow‐up] at 6 month follow‐up as the primary endpoint. Changes in symptoms [New York Heart Association (NYHA) class] and neurohormonal activations [N‐terminal pro‐brain natriuretic peptide (NT‐proBNP)] were also evaluated as secondary endpoints; 341 patients (excluding patients with poor acoustic windows and missing data) were analysed (mean age: 65 ± 10 years; 18% female, median LVEF 30% [inter‐quartile range: 25−34]). At 6 month follow‐up, 82 (24%) patients showed early complete response (LVRR and LVEF ≥ 35%), 55 (16%) early incomplete response (LVRR and LVEF < 35%), and 204 (60%) no response (no LVRR and LVEF < 35%). Non‐ischaemic aetiology, a lower left atrial volume index, and a higher GLS were all independent predictors of LVRR at multivariable logistic analysis (all P < 0.01). A baseline GLS < −9.3% was significantly associated with early response (area under the curve 0.75, P < 0.0001). Left atrial strain was the best predictor of positive changes in NYHA class and NT‐proBNP (all P < 0.05). Conclusions: Speckle tracking echocardiography parameters at baseline could be useful to predict LVRR and clinical response to sacubitril–valsartan and could be used as a guide for treatment in patients with HFrEF. [ABSTRACT FROM AUTHOR]

(1) Background: Previous studies showed left ventricular (LV) and left atrial (LA) improvement and reverse remodeling after therapy with Sacubitril/Valsartan (S/V) in patients affected by heart failure with reduced ejection fraction (HFrEF). Therefore, we sought to investigate predictors of LA structural and functional reverse remodeling (LARR) in this setting of patients after therapy with S/V, focusing on left atrial strain parameters, such as peak atrial longitudinal strain (PALS). (2) Methods: Patients with HFrEF underwent clinical and echocardiographic evaluation at baseline and after six months of therapy with S/V. Measures of LA structure (LA volume index, LAVi) and function (LA emptying fraction (LAEF), PALS, LA conduit strain and peak atrial contraction strain (PACS) were also analyzed. Patients were divided in two groups, those with a LARR (relative reduction in LAVi > 15%, LARR+) and those without (LARR−). (3) Results: A total of 47 consecutive patients (66 ± 8 years, 85% male, mean LVEF 28 ± 6%) were enrolled in the study and followed up. A significant increase of LAEF (46 ± 13 vs. 37 ± 11%, p < 0.001) and a significant reduction of LAVi (42 ± 15 vs. 45 ± 15 mL/m2, p = 0.008) were found after 6 months of S/V therapy; 47% of the population showed LA reverse remodeling. LA strain parameters, PALS (19 ± 8 vs. 15 ± 7 %, p < 0.001) and LA conduit (−9.7 ± 5.2% vs. −7.6 ± 4.1%, p = 0.007) significantly improved after 6 months of S/V therapy. At multivariable stepwise regression analysis, changes in LV End Diastolic Volume (LVEDV) and PALS were significantly proportional to changes in LAVi values. (4) Conclusions: Six months of treatment with S/V in patients with HFrEF was associated with an improvement in LA functional reverse remodeling in a real-world scenario. LARR was not significantly correlated to baseline echocardiographic variables, but was proportional to changes in LV volumes and LA strain parameters. Finally, after S/V therapy, a strict connection between LA and LV reverse remodeling and between LA anatomical and functional reverse remodeling seems to be outlined. [ABSTRACT FROM AUTHOR]

Penetrating injuries of the heart, named penetrating cardiac injury (PCI), may cause hemorrhagic shock as well as cardiac tamponade, leading to death if not treated immediately. This systematic review aims to highlight the main aspects of penetrating cardiac injuries after firearm wounds. The cases of 39 subjects (age 37.05 + 15.4) were selected (6 fatal cases). Specifically, 4/39 cases involved subjects under 18 y.o.; analyzing the entrance wound, in 30/39 cases it was located in the anterior chest, 4/39 in the posterior chest, 3/39 in the shoulder/axilla area, 1/39 in the neck, and 1/39 in the pelvis (gluteus). The exit wound was found in only 3/39 cases. Several factors may influence the prognosis: firstly, prompt intervention represents a crucial point, then considering the complications related to PCI, the most important are myocardial infarction, and projectile migration with embolization. The mortality rate is related to: (1) area and severity of the heart injury; (2) duration of transport and intervention; (3) contemporary lesion to other organ/s; (4) the quantity of blood lost; (5) and presence/absence of cardiac tamponade. Based on these findings, a correct approach in the management of PCI may be considered important from a forensic point of view, both as regards to medical liability and from the trial perspective. [ABSTRACT FROM AUTHOR]

Aims: The angiotensin receptor‐neprilysin inhibitor (ARNI) sacubitril/valsartan (Sac/Val) demonstrated to be superior to enalapril in reducing hospitalizations, cardiovascular and all‐cause mortality in patients with ambulatory heart failure and reduced ejection fraction (HFrEF), in particular when it is maximally up‐titrated. Unfortunately, the target dose is achieved in less than 50% of HFrEF patients, thus undermining the beneficial effects on the outcomes. In this study, we aimed to evaluate the role of Sac/Val and its titration dose on reverse cardiac remodelling and determine which echocardiographic index best predicts the up‐titration success. Methods and results: From January 2020 to June 2021, we retrospectively identified 95 patients (65.6 [59.1–72.8] years; 15.8% females) with chronic HFrEF who were prescribed Sac/Val from the HF Clinics of 5 Italian University Hospitals and evaluated the tolerability of Sac/Val high dose (the ability of the patient to achieve and stably tolerate the maximum dose) as the primary endpoint in the cohort. We used a multivariable logistic regression analysis, with a stepwise backward selection method, to determine the independent predictors of Sac/Val maximum dose tolerability, using, as candidate predictors, only variables with a P‐value < 0.1 in the univariate analyses. Candidate predictors identified for the multivariable backward logistic regression analysis were age, sex, body mass index (BMI), chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), dyslipidaemia, atrial fibrillation, systolic blood pressure (SBP), baseline tolerability of ACEi/ARBs maximum dose, left ventricle global longitudinal strain (LVgLS), LV ejection fraction (EF), tricuspid annulus plane systolic excursion (TAPSE), right ventricle (RV) fractional area change (FAC), RV global and free wall longitudinal strain (RVgLS and RV‐FW‐LS). After the multivariable analysis, only one categorical (ACEi/ARBs maximum dose at baseline) and three continuous (younger age, higher SBP, and higher TAPSE), resulted significantly associated with the study outcome variable with a strong discriminatory capacity (area under the curve 0.874, 95% confidence interval (CI) (0.794–0.954) to predict maximum Sac/Val dose tolerability. Conclusions: Our study is the first to analyse the potential role of echocardiography and, in particular, of RV dysfunction, measured by TAPSE, in predicting Sac/Val maximum dose tolerability. Therefore, patients with RV dysfunction (baseline TAPSE <16 mm, in our cohort) might benefit from a different strategy to titrate Sac/Val, such as starting from the lowest dose and/or waiting for a more extended period of observation before attempting with the higher doses. [ABSTRACT FROM AUTHOR]

Background: Observational studies have demonstrated that treatment with sacubitril/valsartan may improve left ventricular (LV) systolic and diastolic function in subjects with reduced LV ejection fraction (LVEF) in real‐world studies. Subjects with heart failure and reduced EF (HFrEF), however, are also characterized by an impaired right ventricular (RV) function. We therefore aimed to evaluate whether also RV function may improve after S/V therapy and possible predictors of RV improvement could be identified at echocardiography and tissue Doppler imaging. Methods: Fifty consecutive patients (67 ± 8 years, LVEF 28 ± 6%, male 86%) with chronic HFrEF and NYHA class II‐III were followed up for 6 months after therapy with S/V. LV&RV function was assessed at baseline and after 6 months of therapy. Results: After 6‐month therapy with S/V a significant improvement was shown in the following echocardiography parameters assessing RV function: PAsP (31 ± 11 vs. 35 ± 10 mmHg, p < 0.001), TAPSE (19 ± 3 vs. 18 ± 3 mm, p < 0.001), RV FAC (38 ± 7 vs. 34 ± 6 mm, p < 0.001), RV S' (12 ± 2 vs. 10 ± 2 cm/s, p < 0.001), RV‐FW‐LS (−20 ± 5 vs. −18 ± 5%, p < 0.001), RV‐4Ch‐LS (−16 ± 5 vs. −14 ± 5%, p < 0.001). At multivariable analysis improvement in RV‐FW‐LS was associated to baseline levels of RV S' (r 0.75, p < 0.01) and RAV (r –0.32, p < 0.05). Conclusions: In a real‐world scenario, 6‐month therapy with S/V was associated with an improved RV function in HFrEF. RV function improvement may be predicted by assessing baseline RV S' and right atrial volume values. [ABSTRACT FROM AUTHOR]

A high-performance liquid chromatographic method for the simultaneous determination of di(2-ethylhexyl)phthalate (DEHP) and its major metabolite mono(2-ethylhexyl)phthalate (MEHP) in seminal plasma was developed and validated. The method involves liquid-liquid extraction followed by isocratic reversed-phase chromatography with diode-array detection. The recovery, selectivity, linearity, precision and accuracy of the method were evaluated from the analysis of spiked seminal plasma samples. The effect of mobile-phase composition and pH on the retention of the target analytes was investigated. The limits of detection were 0.010 and 0.015 µg/mL, for DEHP and MEHP, respectively. This method was used to analyze real samples in support of clinical studies on these potential endocrine disruptors. Copyright © 2007 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Di-(2-ethylhexyl)phthalate (DEHP) is the most commonly used plasticizer in flexible polyvinylchloride formulations, and is a widespread ubiquitous environmental contaminant. A potential role of exposure to DEHP and its primary metabolite, monoethylhexylphthalate (MEHP), on women's reproductive function is suggested in the current study. The aim of the study was to test serum concentrations of DEHP and/or MEHP in women with uterine fibromatosis. Two groups of women were enrolled in the study: (i) women with uterine fibromatosis undergoing surgical menopause ( n = 15) and (ii) healthy women ( n = 20). Serum DEHP and MEHP concentrations were measured by high-performance liquid chromatography. Serum MEHP distribution was found to be non-Gaussian ( p = 0.001) while serum DEHP distribution was compatible with a normal curve ( p = 0.141). Patients with uterine fibromatosis showed significantly lower serum MEHP concentrations (median [interquartile range]: 0 [0–0] µg/ml, range: 0–0.57 µg/ml) than controls (0.42 [0–0.51] µg/ml, range: 0–1.20 µg/ml, z = -2.93, p = 0.0034). Likewise, serum DEHP concentrations in women with fibromatosis were found to be significantly lower than in controls (patients: 0.27 ± 0.096 µg/ml (mean ± standard deviation (SD)), range: 0.14–0.59 µg/ml vs. controls: 0.30 ± 0.14 µg/ml (mean ± SD), range: 0–0.63 µg/ml; t = 3.212, df = 33, difference: -0.325 (95% confidence interval: -0.5309, -0.1191), p = 0.0029). In conclusion, the present findings indicate for the first time that serum DEHP and MEHP concentration are lower in women with uterine fibromatosis, suggesting a possible correlation between phthalate esters and fibromatosis pathology. [ABSTRACT FROM AUTHOR]

In the present work are reported the results of a monitoring on a vast scale, carried out through evaluation of opportune chemical parameters, of the pollution state of the agricultural-industrial settlement of the Fucino Plain. The parameters took into consideration have been the presence of wide consumption pesticides and of ionic species as Cl-, NO2-, NO3-, NH4+ the quantification of the dissolved oxygen, of the temperature, of the conductivity, of pH and eH. Collected data are used for chemometric elaboration. The water systems examined, by means of drawing campaigns carried out at regular intervals in winter, spring, summer, and autumnal seasons, are represented by superficial waters constituting a network of irrigation canals fed by stratum and meteoric waters. In this work are reported the results relative to the drawing campaigns. [ABSTRACT FROM AUTHOR]

A sensitive high performance liquid chromatographic(HPLC) method with ultraviolet absorption detection(230 nm) was developed and validated for the determination of a phosphodiesterase V inhibitor, Sildenafil, in seminal plasma. A single step liquid–liquid extraction procedure using ethyl acetate was performed to recover sildenafil from 1.0 mL of seminal plasma combined with 200 µL of NaOH 0.1 M. A symmetry C18 column(150 × 4.6 mm I.D. 5 µm) was used as a stationary phase and the mobile phase consisted of 32% acetonitrile and 68% phosphoric acid(0.016 M; pH 5.3) at a flow rate of 1.0 mL/min. The quantitation limit was 5 ng/mL. Intra- and inter-day relative standard deviation(RSD) did not exceed 6.6%. This HPLC method has been successfully used in medical laboratories to assay seminal plasma samples for studies on the treatment with sildenafil. [ABSTRACT FROM AUTHOR]

A method for the simultaneous determination of di(2-ethylhexyl)phthalate and its major metabolite mono(2-ethylhexyl)phthalate in human plasma by high-performance liquid chromatography is described. The procedure, linear in the concentration range 0.05–5.0 ppm, is simple and rapid and allows accurate and precise results. The limits of detection for di(2-ethylhexyl)phthalate and mono(2-ethylhexyl)phthalate were 0.05 ppm. [ABSTRACT FROM AUTHOR]

The development and validation of a reversed-phase liquid chromatographic method for the determination of lomefloxacin in seminal plasma is described. Lomefloxacin was extracted on a solid-phase cartridge and separated on a reversed-phase column with acetonitrile in phosphate buffer at pH 7.0 as mobile phase. The solid-phase extraction showed high recovery for lomefloxacin from seminal plasma samples. The chromatographic peaks height ratio of lomefloxacin and internal standard, obtained by fluorimetric detection, was used for quantitative analysis. The proposed method was validated with respect to accuracy, precision, linearity, and specificity. Also, the method was determined to be robust with regards to the following parameters: mobile phase, apparent pH; mobile phase organic content. The percent recoveries of lomefloxacin, the limit of detection (LOD) and limit of quantitation (LOQ) for the HPLC method have been determined. This high-performance liquid chromatographic method has been successfully used in medical laboratories to assay seminal plasma samples for studies on the treatment of chronic bacterial infections with lomefloxacin. [ABSTRACT FROM AUTHOR]