The Changing Role of Loop Diuretics in Heart Failure Management across the Last Century.

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.

Rationale and design of the Biventricular Evaluation of Gliflozins effects In chroNic Heart Failure: BEGIN-HF study.

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.

Left Atrial Functional Remodeling in Patients with Chronic Heart Failure Treated with Sacubitril/Valsartan.

(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.

Systematic Review of Penetrating Cardiac Injury by a Firearm: Forensic Implications.

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.

The Evolving Phenotypes of Cardiovascular Disease during COVID-19 Pandemic.

COVID-19 pandemic has negatively impacted the management of patients with acute and chronic cardiovascular disease: acute coronary syndrome patients were often not timely reperfused, heart failure patients not adequately followed up and titrated, atrial arrhythmias not efficaciously treated and became chronic. New phenotypes of cardiovascular patients were more and more frequent during COVID-19 pandemic and are expected to be even more frequent in the next future in the new world shaped by the pandemic. We therefore aimed to briefly summarize the main changes in the phenotype of cardiovascular patients in the COVID-19 era, focusing on new clinical challenges and possible therapeutic options.

Deformation Imaging by Strain in Chronic Heart Failure Over Sacubitril-Valsartan: A Multicenter Echocardiographic Registry.

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.

Sacubitril/valsartan reduces indications for arrhythmic primary prevention in heart failure with reduced ejection fraction: insights from DISCOVER-ARNI, a multicenter Italian register.

Aims: This sub-study deriving from a multicentre Italian register [Deformation Imaging by Strain in Chronic Heart Failure Over Sacubitril-Valsartan: A Multicenter Echocardiographic Registry (DISCOVER)-ARNI] investigated whether sacubitril/valsartan in addition to optimal medical therapy (OMT) could reduce the rate of implantable cardioverter-defibrillator (ICD) indications for primary prevention in heart failure with reduced ejection fraction (HFrEF) according to European guidelines indications, and its potential predictors. Methods and results: In this observational study, consecutive patients with HFrEF eligible for sacubitril/valsartan from 13 Italian centres were included. Lack of follow-up or speckle tracking data represented exclusion criteria. Demographic, clinical, biochemical, and echocardiographic data were collected at baseline and after 6 months from sacubitril/valsartan initiation. Of 351 patients, 225 (64%) were ICD carriers and 126 (36%) were not ICD carriers (of whom 13 had no indication) at baseline. After 6 months of sacubitril/valsartan, among 113 non-ICD carriers despite having baseline left ventricular (LV) ejection fraction (EF) ≤ 35% and New York Heart Association (NYHA) class = II-III, 69 (60%) did not show ICD indications; 44 (40%) still fulfilled ICD criteria. Age, atrial fibrillation, mitral regurgitation > moderate, left atrial volume index (LAVi), and LV global longitudinal strain (GLS) significantly varied between the groups. With receiver operating characteristic curves, age ≥ 75 years, LAVi ≥ 42 mL/m2 and LV GLS ≥-8.3% were associated with ICD indications persistence (area under the curve = 0.65, 0.68, 0.68, respectively). With univariate and multivariate analysis, only LV GLS emerged as significant predictor of ICD indications at follow-up in different predictive models. Conclusions: Sacubitril/valsartan may provide early improvement of NYHA class and LVEF, reducing the possible number of implanted ICD for primary prevention in HFrEF. Baseline reduced LV GLS was a strong marker of ICD indication despite OMT. Early therapy with sacubitril/valsartan may save infective/haemorrhagic risks and unnecessary costs deriving from ICDs.

Predictors of sacubitril/valsartan high dose tolerability in a real world population with HFrEF.

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.

Pharmacological Anti-Remodelling Effects of Disease-Modifying Drugs in Heart Failure with Reduced Ejection Fraction.

Cardiac remodelling is an adverse phenomenon linked to heart failure progression and an important contributor to heart failure severity. Cardiac remodelling could represent the real therapeutic goal in the treatment of patients with heart failure with reduced ejection fraction, being potentially reversed through different pharmacotherapies. Currently, there are well-established drugs such as angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers and ß-blockers with anti-remodelling effects; recently, angiotensin receptor neprilysin inhibitor effects on inhibiting cardiac remodelling (improving N-terminal pro-B-type natriuretic peptide levels, echocardiographic parameters of reverse cardiac remodelling and right ventricular function in patients with heart failure with reduced ejection fraction) were demonstrated. More recently, hemodynamic consequences of gliflozins, reduced cardiac hydrostatic pressure as a possible cause of ventricular remodelling and hypertrophy were proposed to explain potential anti-remodelling effects of gliflozins. Gliflozins exert their cardioprotective effects by attenuating myofibroblast activity and collagen-mediated remodelling. Another postulated mechanism is represented by the reduction in sympathetic activity, through the reduction in renal afferent nervous activity and the suppression of central reflex mechanisms. Benefits of gliflozins on left ventricular hypertrophy, dilation, and systolic and diastolic function were also described. In this review, we aimed to provide a wide overview on cardiac remodelling with a particular focus on possible anti-remodelling effects of angiotensin receptor neprilysin inhibitors and gliflozins.

Remodelling is inversely proportional to left ventricular dimensions in a real-life population of patients with chronic heart failure after therapy with sacubitril/valsartan.

BACKGROUND: Left ventricular (LV) remodelling is a major mechanism underlying disease progression in patients with heart failure (HF) with reduced ejection fraction (EF). Previous studies that LVEF improvement and reverse remodelling can be achieved after therapy with Sacubitril/Valsartan in real-world settings. Therefore, we sought to investigate possible predictors of LV remodelling, in particular echocardiographic parameters derived by Tissue Doppler Imaging. METHODS: Patients with chronic HF, LV dysfunction (EF < 35%), NYHA class II-III were followed up between September 2016 and January 2019. All patients underwent clinical and echocardiography follow up at baseline and after 12 months of therapy with sacubitril/valsartan. RESULTS: Fifty-four consecutive outpatients were enrolled in the study. At follow-up visit LVEF (38 ± 9 vs. 30 ± 5%, p < 0.0001), LVEDD (61 ± 8 vs. 62 ± 8 mm, p = 0.0085), LVESV (114 ± 57 vs. 130 ± 56 mm3, p = 0.0001), mitral regurgitation severity (1 ± 1 vs. 2 ± 1, p < 0.0001), and left atrial area (23 ± 6 vs. 24 ± 6 mm2, p = 0.0121) changed compared to the baseline value. Changes in LVEF (follow up vs baseline) correlated with baseline levels of heart rate (r = 0.24, p = 0.048), LVEDD (r= -0.33, p = 0.004), LVEDV (r= -0.39, p = 0.001), LVESV (r = 0.37, p = 0.002), and changes in LVESV (r=-0.34, p = 0.006). Correlations remained significant even after correction at multivariate analysis including age and gender. CONCLUSIONS: Treatment with sacubitril/valsartan in patients with systolic dysfunction is associated with an improvement in LVEF in a real world scenario. Smaller LV volumes are associated with better reverse LV remodelling.

Switch to SGLT2 Inhibitors and Improved Endothelial Function in Diabetic Patients with Chronic Heart Failure.

PURPOSE: The use of sodium-glucose-cotransporter-type-2 inhibitors (SGLT2i) was associated in previous studies with an improved vascular function in non-human experimental models. We therefore sought to evaluate possible changes in endothelial function assessed by flow-mediated dilation (FMD) in patients with chronic heart failure (CHF) and type-2 diabetes mellitus (T2DM), switching from other oral hypoglycemic agents to SGLT2i in an observational study. METHODS: Twenty-two consecutive outpatients with CHF and T2DM were enrolled after switching to SGLT2i therapy, and compared with 23 consecutive controls from the same registry comparable for principal clinical characteristics. In all patients, endothelial function was assessed by FMD at baseline and after 3 months of follow-up. RESULTS: Three months of therapy with SGLT2i were associated with a statistically significant improvement in endothelial function (19.0 ± 5.7% vs 8.5 ± 4.1%, p < 0.0001); baseline levels of FMD were comparable between groups (p n.s.). Therapy with SGLT2i was significantly associated to improved FMD levels even at multivariable stepwise regression analysis (p < 0.001). CONCLUSIONS: Switch to SGLT2i in patients with CHF and T2DM was associated in an observational non-randomized study with an improved endothelial function.

Predictors of right ventricular function improvement with sacubitril/valsartan in a real-life population of patients with chronic heart failure.

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.

New Targets in Heart Failure Drug Therapy.

Despite recent advances in chronic heart failure management (either pharmacological or non-pharmacological), the prognosis of heart failure (HF) patients remains poor. This poor prognosis emphasizes the need for developing novel pathways for testing new HF drugs, beyond neurohumoral and hemodynamic modulation approaches. The development of new drugs for HF therapy must thus necessarily focus on novel approaches such as the direct effect on cardiomyocytes, coronary microcirculation, and myocardial interstitium. This review summarizes principal evidence on new possible pharmacological targets for the treatment of HF patients, mainly focusing on microcirculation, cardiomyocyte, and anti-inflammatory therapy.

Serum Uric Acid and Left Ventricular Mass in Essential Hypertension.

Serum uric acid (sUA) has been associated with cardiovascular risk. Although the recent mechanistic hypothesis poses the basis for the association between sUA and left ventricular mass index (LVMi), the issue remains poorly investigated in a clinical setup. Through a retrospective analysis of the database of the departmental Hypertension Clinic of University Hospital of Salerno Medical School, we identified 177 essential hypertensives (age 60.3 ± 13.3 years; 85 men), free from uric acid-modulating medications and severe chronic kidney disease, and whose sUA values, anthropometric, clinical, and echocardiographic data were available. In the studied cohort, the average duration of hypertension was 8.4 ± 7.1 years. LVMi associated with classical determinants, such as age, blood pressure, and kidney function, although after multivariate correction, only age remained significant. Also, sUA correlated positively with LVMi, as well as body size, metabolism, and kidney function. In a multivariate analysis, sUA confirmed the independent association with LVMi. Also, levels of sUA >5.6 mg/dl are associated with larger cardiac size. We confirmed our data in a replicate analysis performed in a larger population (1,379 hypertensives) from an independent clinic. Our results demonstrate that sUA increases with LVMi, and a cutoff of 5.6 mg/dl predict larger LV sizes. Our data suggest that hyperuricemia might help to stratify the risk of larger cardiac size in hypertensives.

Switch to direct anticoagulants and improved endothelial function in patients with chronic heart failure and atrial fibrillation.

BACKGROUND: Chronic heart failure (CHF) is characterized by higher rates of atrial fibrillation (AF) and endothelial dysfunction (ED). First line anticoagulant therapy in AF is represented by direct oral anticoagulants (DOACs); several patients, however, are still treated with vitamin-K inhibitors. The use of DOACs is associated in previous studies with an improved vascular function. We therefore sought to evaluate possible changes in endothelial function assessed by flow-mediated dilation (FMD) in patients with CHF and AF shifting from warfarin to DOACs. METHODS: Forty-three consecutive outpatients were enrolled in the study. FMD was assessed at baseline and after 4 months. Patients were compared according to AC therapy. RESULTS: After the first measurement of FMD, 18 patients "switched" to DOACs because of poor compliance to warfarin therapy or time in therapeutic range, 19 patients continued to use DOACs, 6 warfarin. "Switched" patients to DOACs therapy showed an improved FMD (19.0 ± 6.6% vs 3.8 ± 1.3%, p < 0.0001); C-reactive protein (CRP) levels decreased in "switched" patients from 1.4 ± 0.5 to 1.0 ± 0.7 mg/dl (p < 0.05). FMD and CRP changes were not significant in patients who did not changed anticoagulant therapy. In switched patients, changes in CRP levels were proportional to FMD changes (r = -0.50, p < 0.05). Shifting from warfarin to DOACs was significantly correlated to improved FMD levels even at multivariable analysis (p < 0.05). CONCLUSIONS: Switch from warfarin to DOACs in patents with CHF and AF was associated in an observational non randomized study with an improved endothelial function. Changes in FMD values were related to changes in CRP levels.

Sacubitril/valsartan improves right ventricular function in a real-life population of patients with chronic heart failure: The Daunia Heart Failure Registry.

BACKGROUND: Previous studies and case-series showed improvement in left ventricular (LV) function and reverse remodeling after sacubitril/valsartan therapy in real-world studies. We therefore aimed to evaluate whether also right ventricular (RV) function may improve after sacubitril/valsartan therapy. METHODS: Sixty consecutive patients with chronic heart failure and NYHA class II-III were followed up for 12 months after therapy with sacubitril/valsartan. Left and (RV) function was assessed at baseline and after 12 months of therapy. RESULTS: At 12-month control, therapy with sacubitril/valsartan was associated with a significant improvement in a series of echo parameters: LVEF (p < 0.05), LV end-systolic volume (p < 0.01), left atrium area (p < 0.05).Right ventricular echo parameters were also improved after sacubitril/valsartan therapy: PAsP (31.0 ± 12.8 vs 34.7 ± 12.5 mmHg, p < 0.05), TAPSE (17.8 ± 3.9 vs 16.5 ± 4.0 mm, p < 0.001); mean PAsP reduction was 3.7 ± 11.4 mmHg (-6.3 ± 37.7%), mean TAPSE increase 1.3 ± 2.5 mm (+9.5 ± 15.7%).Indexed (%) improvement in PAsP (r 0.33, p < 0.01) and TAPSE (r -0.42, p < 0.01) values were proportional to baseline levels. Improvement in PAsP and TAPSE were independent of left ventricular improvements except for PAsP and end-systolic volumes (r 0.44, p < 0.01). CONCLUSIONS: In a real world scenario, sacubitril/valsartan was associated with an improved RV function.

Liver disease and heart failure.

INTRODUCTION: Several systemic conditions, inflammatory disease, infections and alcoholism, may affect both the heart and the liver. Common conditions, such as the non-alcoholic fatty liver disease (NAFLD), may increase the risk of cardiac dysfunction. Patients with acute decompensated HF (ADHF) may develop acute ischemic hepatitis and, chronic HF patients may develop congestive hepatopathy (CH). EVIDENCE ACQUISITION: Laboratory anomalies of hepatic function may predict the outcome of patients with advanced HF and the evaluation of both cardiac and hepatic function is very important in the management of these patients. In clinically apparent ischemic hepatitis more than 90% of patients have some right-sided HF. There are systemic disorders characterized by the accumulation of metals or by metabolism defects that may affect primarily the liver but also the heart leading to symptomatic hypertrophic cardiomyopathy (HCM). EVIDENCE SYNTHESIS: Abnormal LFTs indicate the mechanism of liver injury: liver congestion or liver ischemia. In AHF, it's important an adequate evaluation of heart and liver function in order to choose the treatment in order to ensure stable hemodynamic as well as optimal liver function. CONCLUSIONS: Measurements of LFTs should be recommended in the early phase of ADHF management. Physicians with interest in HF should be trained in the evaluation of LFTs. It's very important for cardiologists to know the systemic diseases affecting both heart and liver and the first imaging or laboratory findings useful for a diagnosis. it is very important for internists, nephrologists, cardiologists, primary physicians and any physicians with interest in treating HF to recognize such signs and symptoms belong to rare diseases and liver diseases that could be mistaken for HF.

Medical Records Quality as Prevention Tool for Healthcare-Associated Infections (HAIs) Related Litigation: a Case Series.

BACKGROUND: Healthcare-associated infections are one of the most serious Public Health concern, as they prolong the length of hospitalization, reduce the quality of life, and increase morbidity and mortality. Despite they are not completely avoidable, the number of healthcare-associated infections related to negligence claims has risen over the last years, contributing to remarkable economic and reputation losses of Healthcare System. METHODS: In this regard, several studies suggested a key role of medical records quality in determining medical care process, risk management and preventing liability. Clinical documentation should be able to demonstrate that clinicians met their duty of care and did not compromise patient's safety. RESULTS: Therefore, it has a key role in assessing healthcare workers' liability in malpractice litigation. Our risk management experience has confirmed the role of medical records accuracy in preventing hospital liability and improving the quality of medical care. CONCLUSION: In the presented healthcare-associated infections cases, evidence-based and guidelinesbased practice, as well as a complete/incomplete medical record, have shown to significantly affect the verdict of the judicial court and inclusion/exclusion of hospital liability in healthcare-associated infections related claims.

The Italian version of the quick mild cognitive impairment (Qmci-I) screen: normative study on 307 healthy subjects.

OBJECTIVE: To devise an Italian version of the quick mild cognitive impairment screen (Qmci) and to obtain normative data. METHODS: An Italian version of the Qmci screen (Qmci-I) was administered to 307 subjects free from cognitive impairment. The normative sample was divided into three age levels (50-59; 60-69 and 70-80 years) and four education levels (3-5; 6-8; 9-13; >13 years of school attendance). Multiple regression analyses were used to evaluate the effect of age, sex and schooling on Qmci-I scores (overall and by domains) and to calculate cut-off values, with reference to the confidence interval on the fifth centile. RESULTS: The mean Qmci-I score was 64/100 (SD = 11). The age variable showed a significant negative effect on the overall Qmci-I score, with older people performing worse than younger ones. Conversely, education was associated with higher scores. Significant effects of age and education affected logical memory alone. For the other domains, the following effects were found: (1) higher age associated with lower scores on delayed recall; (2) higher education levels associated with higher scores on immediate recall, clock drawing and word fluency. The adjusted cut-off score for the Qmci-I screen in this sample was 49.4. Qmci-I scores were weakly correlated with those of MMSE (rho = 0.20). CONCLUSIONS: The Qmci-I is a rapid and multi-domain short cognitive screening instrument useful for evaluating cognitive functions. However, like other screening tools, it is significantly influenced by age and education, requiring normative data and correction of values when used in the clinical practice.