[ANMCO Position paper: Obesity in adults - A clinical primer]. / Position paper ANMCO: Obesità nell'adulto ­ Clinical primer.

Obesity is a chronic and relapsing disease due to the coexistence of a patient with predisposing individual characteristics and an obesogenic environment. The recent acquisition of detailed knowledge on the mechanisms underlying the energetic homeostasis paved the way to more effective therapeutic hypotheses as compared to traditional treatments. Since obesity is a complex issue, it requires a multidisciplinary approach which is difficult to implement. However, new drugs appear promising. Currently, therapeutic success is discrete in the short term, but unsatisfying in the long term due to the high probability of body weight gain. Cardiologists play a key role in managing patients with obesity, but they are not used to manage them. The aim of this document is to summarize knowledge that clinicians need to have to appropriately manage these patients. The paper emphasizes the pivotal role of an appropriate relationship with the patient to embark on a successful treatment journey. We analyze the criteria commonly used to diagnose obesity and point out strengths and limitations of different criteria. Furthermore, we discuss the figure of the obesitologist and the role of the cardiologist. In addition, we report the main components of an effective therapeutic strategy, from educational questions to pharmacological options.

Hyperkalaemia in Cardiological Patients: New Solutions for an Old Problem.

Hyperkalaemia is one of the most common electrolyte disorders in patients with cardiovascular disease (CVD). The true burden of hyperkalaemia in the real-world setting can be difficult to assess, but in population-based cohort studies up to 4 in 10 patients developed hyperkalaemia. In addition to drugs interfering with potassium metabolism and food intake, several conditions can cause or worsen hyperkalaemia, such as advanced age, diabetes, and chronic kidney disease. Mortality, cardiovascular morbidity, and hospitalisation are higher in patients with hyperkalaemia. Hyperkalaemia represents a major contraindication or a withholding cause for disease-modifying therapies like renin-angiotensin-aldosterone inhibitors (RAASi), mainly mineralocorticoid receptor antagonists. Hyperkalaemia can be also classified as acute and chronic, according to the onset. Acute hyperkalaemia is often a life-threatening emergency requiring immediate treatment to avoid lethal arrhythmias. Therapy goal is cell membrane stabilisation by calcium administration, cellular intake, shift of extracellular potassium to the intracellular space (insulin, beta-adrenergic agents, sodium bicarbonate), and increased elimination with diuretics or dialysis. Chronic hyperkalaemia was often managed with dietary counselling to prevent potassium-rich food intake and tapering of potassium-increasing drugs, mostly RAASi. Sodium polystyrene sulphonate, a potassium binder, was the only therapeutic option. Recently, new drugs such as patiromer and sodium zirconium cyclosilicate give new opportunities for the treatment of hyperkalaemia, as they proved to be safe, well tolerated, and effective. Aim of this review is to describe the burden of hyperkalaemia in cardiovascular patients, its direct and indirect effects, and the therapeutic options now available in the acute and chronic setting.

Pharmacoutilization and adherence to sacubitril/valsartan in real world: the REAL.IT study in HFrEF.

AIMS: The current European Society of Cardiology (ESC) guidelines provide clear indications for the treatment of acute and chronic heart failure (HF). Nevertheless, there is a constant need for real-world evidence regarding the effectiveness, adherence, and persistence of drug therapy. We investigated the use of sacubitril/valsartan for the treatment of HF with reduced ejection fraction in real-world clinical practice in Italy. METHODS AND RESULTS: An observational, retrospective, non-interventional cohort study based on electronic medical records from nine specialized hospital HF centres in Italy was carried out on patients with prescription of sacubitril/valsartan. Overall, 948 patients had a prescription of sacubitril/valsartan, with 924 characterized over 6 months and followed up for 12 months. Pharmacoutilization data at 1 year of follow-up were available for 225 patients {mean age 69.7 years [standard deviation (SD) = 10.8], 81.8% male}. Of those, 398 (45.2%) reached the target dose of sacubitril/valsartan of 97/103 mg in a mean time of 6.9 (SD = 6.2) weeks. Blood pressure and hypotension in 61 patients (65%) and worsening of chronic kidney disease in 10 patients (10.6%) were the main reasons for not reaching the target dose. Approximatively 50% of patients had a change in sacubitril/valsartan dose during follow-up, and 158 (70.2%) were persistent with the treatment during the last 3 months of follow-up. A sensitivity analysis (persistence during the last 4 months of follow-up) showed persistence for 162 patients (72.0%). Adherence data, available for 387 patients, showed full adherence for 205 (53%). Discontinuation (102/717 patients, 14.2%) was mainly due to hypotension and occurred after a mean time of 34.3 (SD = 28.7) weeks. During follow-up, out of 606 patients with available data, 434 patients (71.6%) had an HF add-on drug or drugs concomitant with sacubitril/valsartan. HF-related hospitalization during follow-up was numerically higher in non-persistent (16/67 patients, 23.9%) vs. patients persistent to sacubitril/valsartan (30/158, 19%) (P = 0.405). CONCLUSIONS: Real-world data on the use of sacubitril/valsartan in clinical practice in Italy show a rapid titration to the target dose, high therapeutic adherence enabling a good level of therapeutic management in line with ESC guidelines for patients with reduced ejection fraction.

Improvement in Left and Right Ventricular Function after Introduction of SGLT2 Inhibitors in Heart Failure Outpatients with Reduced Ejection Fraction.

BACKGROUND: Type 2 sodium-glucose cotransporter inhibitors (SGLT2i) are among the main therapeutic options for patients with chronic heart failure with reduced ejection fraction (HFrEF). The aim of this study was to evaluate the effects of SGLT2i on the echocardiographic parameters of left (LV) and right (RV) ventricular function among outpatients with a long history of HFrEF, in optimized therapy. METHODS: We evaluated consecutive patients affected by HFrEF in whom the SGLT2i therapy was prescribed. Following a baseline evaluation (T0), in which SGLT2i was prescribed, patients were re-evaluated at 3 (T3), 6 (T6), and 12 (T12) months. RESULTS: We considered 60 patients for the analysis with a median history of HFrEF of more than seven years in optimal medical and electrical therapy. After SGLT2i therapy, LV ejection fraction and LV global longitudinal strain improved from baseline at T3, T6, and T12. Analogously, RV global and free wall longitudinal strain improved at T3 and T6. CONCLUSIONS: Our study shows that the addition of SGLT2i to the optimized therapy for HFrEF was associated with a significant improvement in both LV and RV function, thus highlighting a possible mechanism responsible for the benefit obtained with this class of drugs.

The Role of Genetics in the Management of Heart Failure Patients.

Over the last decades, the relevance of genetics in cardiovascular diseases has expanded, especially in the context of cardiomyopathies. Its relevance extends to the management of patients diagnosed with heart failure (HF), given its capacity to provide invaluable insights into the etiology of cardiomyopathies and identify individuals at a heightened risk of poor outcomes. Notably, the identification of an etiological genetic variant necessitates a comprehensive evaluation of the family lineage of the affected patients. In the future, these genetic variants hold potential as therapeutic targets with the capability to modify gene expression. In this complex setting, collaboration among cardiologists, specifically those specializing in cardiomyopathies and HF, and geneticists becomes paramount to improving individual and family health outcomes, as well as therapeutic clinical results. This review is intended to offer geneticists and cardiologists an updated perspective on the value of genetic research in HF and its implications in clinical practice.

Introduction of SGLT2 Inhibitors and Variations in Other Disease-Modifying Drugs in Heart Failure Patients: A Single-Centre Real-World Experience.

BACKGROUND: The sodium-glucose cotransporter-2 inhibitors (SGLT2i) have emerged as a crucial therapeutic option for patients with chronic heart failure with reduced ejection fraction (HFrEF). The aim of this study was to evaluate, in a real-world population from a single centre, the feasibility of introducing SGLT2i and their interaction with other recommended drug classes. METHODS: Consecutive patients affected by chronic heart failure (CHF) were evaluated beginning in January 2022. At the baseline clinical visit, both the patient's current medication and the prescribed treatments were recorded. Over a 6- to 12-month follow-up, changes in concomitant therapy were analysed. RESULTS: At baseline, among 350 patients evaluated, only 17 (5%) were already taking SGLT2i: 13 with HFrEF, five with mildly reduced (HFmrEF), preserved (HFpEF) or improved (HFimpEF) ejection fraction. After the baseline assessment, SGLT2i were prescribed to 224 (64%) of the patients, including 179 (84%) with HFrEF, 27 (42%) with HFmrEF/HFimpEF, and 18 (22%) with HFpEF/HFimpEF. After follow-up, SGLT2i therapy was well tolerated and was associated with a significant increase in sacubitril/valsartan prescriptions and a decrease in diuretic use. Finally, a significant improvement in functional status and left ventricular systolic function after SGLT2i therapy was observed. CONCLUSIONS: In this single-centre, real-world study, SGLT2i were primarily prescribed to HFrEF patients who were already on other recommended drug classes for their treatment. Additionally, there was a noticeable enhancement in the prescribed therapy during a short-term follow-up. These findings further bolster the inclusion of this therapeutic approach in regular clinical practice.

The optimal healthy ranges of thyroid function defined by the risk of cardiovascular disease and mortality: systematic review and individual participant data meta-analysis.

BACKGROUND: Reference intervals of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) are statistically defined by the 2·5-97·5th percentiles, without accounting for potential risk of clinical outcomes. We aimed to define the optimal healthy ranges of TSH and FT4 based on the risk of cardiovascular disease and mortality. METHODS: This systematic review and individual participant data (IPD) meta-analysis identified eligible prospective cohorts through the Thyroid Studies Collaboration, supplemented with a systematic search via Embase, MEDLINE (Ovid), Web of science, the Cochrane Central Register of Controlled Trials, and Google Scholar from Jan 1, 2011, to Feb 12, 2017 with an updated search to Oct 13, 2022 (cohorts found in the second search were not included in the IPD). We included cohorts that collected TSH or FT4, and cardiovascular outcomes or mortality for adults (aged ≥18 years). We excluded cohorts that included solely pregnant women, individuals with overt thyroid diseases, and individuals with cardiovascular disease. We contacted the study investigators of eligible cohorts to provide IPD on demographics, TSH, FT4, thyroid peroxidase antibodies, history of cardiovascular disease and risk factors, medication use, cardiovascular disease events, cardiovascular disease mortality, and all-cause mortality. The primary outcome was a composite outcome including cardiovascular disease events (coronary heart disease, stroke, and heart failure) and all-cause mortality. Secondary outcomes were the separate assessment of cardiovascular disease events, all-cause mortality, and cardiovascular disease mortality. We performed one-step (cohort-stratified Cox models) and two-step (random-effects models) meta-analyses adjusting for age, sex, smoking, systolic blood pressure, diabetes, and total cholesterol. The study was registered with PROSPERO, CRD42017057576. FINDINGS: We identified 3935 studies, of which 53 cohorts fulfilled the inclusion criteria and 26 cohorts agreed to participate. We included IPD on 134 346 participants with a median age of 59 years (range 18-106) at baseline. There was a J-shaped association of FT4 with the composite outcome and secondary outcomes, with the 20th (median 13·5 pmol/L [IQR 11·2-13·9]) to 40th percentiles (median 14·8 pmol/L [12·3-15·0]) conveying the lowest risk. Compared with the 20-40th percentiles, the age-adjusted and sex-adjusted hazard ratio (HR) for FT4 in the 80-100th percentiles was 1·20 (95% CI 1·11-1·31) for the composite outcome, 1·34 (1·20-1·49) for all-cause mortality, 1·57 (1·31-1·89) for cardiovascular disease mortality, and 1·22 (1·11-1·33) for cardiovascular disease events. In individuals aged 70 years and older, the 10-year absolute risk of composite outcome increased over 5% for women with FT4 greater than the 85th percentile (median 17·6 pmol/L [IQR 15·0-18·3]), and men with FT4 greater than the 75th percentile (16·7 pmol/L [14·0-17·4]). Non-linear associations were identified for TSH, with the 60th (median 1·90 mIU/L [IQR 1·68-2·25]) to 80th percentiles (2·90 mIU/L [2·41-3·32]) associated with the lowest risk of cardiovascular disease and mortality. Compared with the 60-80th percentiles, the age-adjusted and sex-adjusted HR of TSH in the 0-20th percentiles was 1·07 (95% CI 1·02-1·12) for the composite outcome, 1·09 (1·05-1·14) for all-cause mortality, and 1·07 (0·99-1·16) for cardiovascular disease mortality. INTERPRETATION: There was a J-shaped association of FT4 with cardiovascular disease and mortality. Low concentrations of TSH were associated with a higher risk of all-cause mortality and cardiovascular disease mortality. The 20-40th percentiles of FT4 and the 60-80th percentiles of TSH could represent the optimal healthy ranges of thyroid function based on the risk of cardiovascular disease and mortality, with more than 5% increase of 10-year composite risk identified for FT4 greater than the 85th percentile in women and men older than 70 years. We propose a feasible approach to establish the optimal healthy ranges of thyroid function, allowing for better identification of individuals with a higher risk of thyroid-related outcomes. FUNDING: None.

DAPA-HF applicability: the point of view of a cardiology setting.

Randomised clinical trials, observational studies, and meta-analyses have shown that sodium-glucose cotransporter 2 inhibitors (SGLT2-i) reduce the risk of hospitalisation for heart failure (HF), chronic kidney disease (CKD) progression, and mortality in patients with HF, irrespective of the presence of type 2 diabetes mellitus. However, real-world epidemiology may differ from clinical trial populations, thereby limiting generalisability and delaying the introduction of novel treatments in clinical practice.The aim of the present study was to assess the prevalence of DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) inclusion criteria in a population of HF with reduced ejection fraction (HFrEF) patients enrolled in the Italian Network on Heart Failure (IN-HF) registry.Overall, 3415 IN-HF patients matched the 4744 patients in DAPA-HF, overlapping for most baseline characteristics (e.g. similar average ejection fraction), with a slightly lower prevalence of type 2 diabetes and of HF ischaemic aetiology and a higher percentage of NYHA class II patients. The theoretical eligibility to DAPA-HF in a cardiology setting resulted to be 73%.The availability of an easily accessible database from a large nationwide prospective registry allows to provide insights to clinicians and policy makers on the applicability of the DAPA HF findings to a contemporary population of HFrEF patients followed by cardiologists. It is reasonable to assume that the results of this analysis can be applicable to the entire SGLT2-ir class of drugs.

Atrial paced rhythm and heart rate-dependent worsening of left atrial and ventricular function.

BACKGROUND AND AIM OF THE STUDY: The response to the increase in heart rate (HR) could be characterized by failure in both left ventricular (LV) and left atrial (LA) functions. This study aimed to evaluate the relationship between the increase in paced HR and the changes in LV and LA functions, assessed by two-dimensional speckle tracking analysis. METHODS: In a group of patients with an implantable cardioverter defibrillator (ICD) or pacemaker, the atrial paced rhythm was progressively increased from 60 to 70, from 70 to 80, and from 80 to 90 beats per minute (bpm). For each paced HR, using two-dimensional speckle tracking analysis, LA reservoir (LAr), LA conduit (LAc), LA contraction (LAct), and LV global longitudinal strain (LV-GLS) were evaluated every 10 bpm. RESULTS: Of the 45 patients enrolled, a significant reduction in LAr was observed at higher HR. However, when the patients were dichotomized according to the HR-related response of LV-GLS, the worsening of LAr was observed in those with LV-GLS worsening and not in those without (maximum LAR absolute changes -2.7 ± 7.2% vs. +2.7 ± 7.2%, respectively, p .028). Moreover, the worsening of LA and LV strain measures was associated with an increase in the estimated filling pressures. CONCLUSIONS: In patients with atrial paced rhythm, the increase in HR could be associated with worsening of LA and LV functions, as assessed by two-dimensional speckle tracking analyses. These results offer new data on HR-related atrioventricular function and could be useful for guiding the optimal HR responsiveness of the implanted devices.

Relationship between the strain measures of left atrial function and heart failure worsening.

BACKGROUND: Two-dimensional speckle tracking evaluation (2D-STE) is a useful tool to evaluate the complexity of atrial function by the analysis of the different phases of atrial deformation and by the combination with Doppler measurements of diastolic function. AIM OF THE STUDY: To evaluate the role of the left atrial (LA) strain parameters to predict worsening chronic heart failure (CHF). METHODS: We enrolled outpatients affected by CHF referred to our heart failure unit. Each patient underwent a medical visit, an electrocardiogram (ECG), and an echocardiographic examination. LA function was assessed by 2D-STE. The three phases of LA strain, that is, the reservoir (LAr), the conduit (LAcd), and the contraction (LAct)-were evaluated. Moreover, the ratio between E and LAr (E/LAr) and those between LAr and septal (LAr/Ees), lateral (LAr/Eel), and septal-lateral (LAr/Eem) E/e' were measured. During follow-up, the events related to worsening of heart failure were evaluated. RESULTS: Two hundred eleven patients were enrolled. During a mean follow-up of 14 ± 7 months, 37 patients showed at least one event related to heart failure worsening. At univariate Cox regression analysis, LAr, LAcd, LAct, E/LAr, LAr/Ees, LAr/Eel, and LAr/Eem were all associated with events related to heart failure worsening, but at multivariate regression analyses, only LAr (Hazard Ratio, HR: .95; 95% Confidence Interval, CI: .92-.99; p: .031), LAct (HR: 1.06; 95% CI: 1.01-1.12; p: .027), E/LAr (HR: 1.10; 95%CI: 1.0-1.16; p < .001), LAr/Ees (HR: .57; 95% CI: .37-.87; p: .010), and LAr/Eem (HR: .71; 95% CI: .53-.96; p: .026) remained significantly associated with the events. Finally, in a predictive model including the other relevant echocardiographic parameters LAr < 18%, LAct > -10.0%, LAr/Ees < 1.28, and E/LAr > 3.70 were associated with a statistically significant overall net reclassification improvement. CONCLUSIONS: In CHF patients, the measure of the LA reservoir and contraction by 2D-STE is independently associated with heart failure worsening, but the accuracy in predicting the events is even greater when the reservoir is combined with the Doppler measures of diastolic function.

Renal Oxygen Demand and Nephron Function: Is Glucose a Friend or Foe?

The kidneys and heart work together to balance the body's circulation, and although their physiology is based on strict inter dependence, their performance fulfills different aims. While the heart can rapidly increase its own oxygen consumption to comply with the wide changes in metabolic demand linked to body function, the kidneys physiology are primarily designed to maintain a stable metabolic rate and have a limited capacity to cope with any steep increase in renal metabolism. In the kidneys, glomerular population filters a large amount of blood and the tubular system has been programmed to reabsorb 99% of filtrate by reabsorbing sodium together with other filtered substances, including all glucose molecules. Glucose reabsorption involves the sodium-glucose cotransporters SGLT2 and SGLT1 on the apical membrane in the proximal tubular section; it also enhances bicarbonate formation so as to preserve the acid-base balance. The complex work of reabsorption in the kidney is the main factor in renal oxygen consumption; analysis of the renal glucose transport in disease states provides a better understanding of the renal physiology changes that occur when clinical conditions alter the neurohormonal response leading to an increase in glomerular filtration pressure. In this circumstance, glomerular hyperfiltration occurs, imposing a higher metabolic demand on kidney physiology and causing progressive renal impairment. Albumin urination is the warning signal of renal engagement over exertion and most frequently heralds heart failure development, regardless of disease etiology. The review analyzes the mechanisms linked to renal oxygen consumption, focusing on sodium-glucose management.

Metabolic Regulation in the Development of Cardiovascular Disease and Heart Failure.

The Special Issue "Metabolic Regulation in the Development of Cardiovascular Disease and Heart Failure" focused on how metabolic diseases could cause a predisposition to cardiovascular diseases and, in particular, heart failure due to systolic or diastolic dysfunction or a combination thereof [...].

SGLT2 Inhibitors: Statins or ACE-Inhibitors of the 21st Century?

Current guidelines propose therapeutic algorithms based on left ventricular ejection fraction values and clinical presentations; however, these guidelines do not specify which of the four pillar drugs to start first [...].

Anaemia and Congestion in Heart Failure: Correlations and Prognostic Role.

The aim of this study was to evaluate the relationship between anaemia and biomarkers of central/peripheral congestion in heart failure (HF) and the impact on mortality. We retrospectively evaluated 434 acute/chronic HF (AHF/CHF) patients. Anaemia was defined as haemoglobin levels <12 g/dL (women) or <13 g/dL (men). The brain natriuretic peptide (BNP) and hydration index (HI) were measured. The endpoint of the study was all-cause mortality. Anaemia occurred in 59% of patients with AHF and in 35% with CHF (p < 0.001) and showed a significant correlation with the NYHA functional class and renal function. BNP and HI were significantly higher in patients with anaemia than in those without anaemia. Independent predictors of anaemia included BNP, estimated creatinine clearance (eCrCL), and HI. The all-cause mortality rate was 21%, which was significantly higher in patients with anaemia than in those without anaemia (30% vs. 14%, p < 0.001; hazard ratio: 2.6). At multivariate Cox regression analysis, BNP, eCrCL, and HI were independent predictors for mortality (Hazard ratios: 1.0002, 0.97, and 1.05, respectively), while anaemia was not. Anaemia correlates with HF status, functional class, renal function, BNP, and HI. Anaemia was not an independent predictor for mortality, acting as a disease severity marker in congestive patients rather than as a predictor of death.

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.

[Renal effects of sodium-glucose cotransporter 2 inhibitors in patients with cardiovascular disease with and without chronic kidney disease]. / Gli effetti renali degli inibitori del cotrasportatore sodio-glucosio di tipo 2 in pazienti con malattia cardiovascolare con e senza insufficienza renale cronica.

The kidney plays an important role in maintaining glucose homeostasis which is used as a metabolic substrate, generated through the mechanism of gluconeogenesis and reabsorbed in the glomerular filtrate through the action of sodium-glucose cotransporters 1 and 2 (SGLT1/2) located in the proximal tubule. Recent studies have shown that inhibition of renal glucose reabsorption, achieved through the administration of sodium-glucose cotransporter inhibitors, significantly reduces renal adverse events and exacerbations of heart failure, not only in diabetic patients, with and without confirmed cardiovascular damage, but also in patients with advanced chronic renal failure and in patients with heart failure with reduced ejection fraction regardless of the presence of diabetes. The extent of the benefit was relevant in the various clinical conditions studied, and led to a significant reduction in the major adverse cardiovascular outcomes recorded in each study. In all controlled studies, the efficacy of sodium-glucose cotransporter inhibitors was strongly associated with the reduction in progression of renal damage, as evidenced by the significant reduction in overall mortality obtained in the two studies that enrolled populations of diabetic and non-diabetic patients with advanced chronic renal failure. Both studies were stopped early at the interim analysis due to the evident superiority of the therapy in the treated arm.The purpose of this review is to examine the role of SGLT2/1 both in physiological conditions that in the course of cardio-nephropathy associated or not with type 2 diabetes mellitus and the effect of SGLT2/1 inhibition on clinical outcomes in different cardiovascular risk population enrolled in different randomized controlled clinical trials.

[Rationale and significance of the Italian Network for Cardiac Amyloidosis]. / Razionale e valore fondamentale della Rete Italiana integrata dell'Amiloidosi Cardiaca.

The perspective on amyloidosis has changed deeply over the last 10 years following major advances in diagnosis and treatment options, especially in cardiac amyloidosis. This intrinsically heterogeneous disease exposes to the risk of fragmentation of knowledge and requires the interaction among experts of different specialties and subspecialties. Suspicion of disease, timely recognition and confirmation of final diagnosis, prognostic stratification, clinical management and therapeutic strategies represent essential steps to be taken. Missing or delaying the diagnosis may have dramatic impact on patient outcome, as in the case of chemotherapy in unrecognized light-chain amyloidosis. Therefore, there is an urgent need for the foundation of an Italian Amyloidosis Network to deal with the challenges of this condition and orient clinical management at national and local levels. The present consensus document aims to provide the rationale and scopes of the Italian Amyloidosis Network, which has been conceived as an organizational framework for professionals managing patients with amyloidosis.

Renal resistance index independently predicts worsening of renal function after coronary angiography.

The renal resistance index (RRI) has been demonstrated to be a useful parameter that can detect patients at a high risk of worsening of renal function (WRF). This study was designed to evaluate the role of the RRI in predicting WRF mediated by the intravascular administration of contrast media. We enrolled patients who were referred for coronary angiography. Renal arterial echo-color Doppler was performed to calculate the RRI. WRF was defined as an increase of > 0.3 mg/dL and at least 25% of the baseline value in creatinine concentration 24-48 h after coronary angiography. Among the 148 patients enrolled in this study, 18 (12%) had WRF. In the multivariate logistic analysis, the RRI was independently associated with WRF (odds ratio [OR]: 1.22; 95% confidence interval [CI]: 1.09-1.36; p = 0.001). After angiography, the RRI significantly increased in both patients with and without WRF. In the receiver operating characteristic curve analyses for WRF, the RRI at baseline and after angiography showed similar accuracy, and the best cutoff value for predicting WRF was 70%. In patients undergoing coronary angiography, the RRI is independently associated with WRF, probably because it provides more accurate information about cardiorenal pathophysiological factors and reflects kidney hemodynamic status and flow reserve.

Does the Measurement of Ejection Fraction Still Make Sense in the HFpEF Framework? What Recent Trials Suggest.

Left ventricular ejection fraction (LVEF) is universally accepted as a cardiac systolic function index and it provides intuitive interpretation of cardiac performance. Over the last two decades, it has erroneously become the leading feature used by clinicians to characterize the left ventricular function in heart failure (HF). Notably, LVEF sets the basis for structural and functional HF phenotype classification in current guidelines. However, its diagnostic and prognostic role in patients with preserved or mildly reduced contractile function is less clear. This is related to several concerns due to intrinsic technical, methodological and hemodynamic limitations entailed in LVEF measurement that do not describe the chamber's real contractile performance as expressed by pressure volume loop relationship. In patients with HF and preserved ejection fraction (HFpEF), it does not reflect the effective systolic function because it is prone to preload and afterload variability and it does not account for both longitudinal and torsional contraction. Moreover, a repetitive measurement could be assessed over time to better identify HF progression related to natural evolution of disease and to the treatment response. Current gaps may partially explain the causes of negative or neutral effects of traditional medical agents observed in HFpEF. Nevertheless, recent pooled analysis has evidenced the positive effects of new therapies across the LVEF range, suggesting a potential role irrespective of functional status. Additionally, a more detailed analysis of randomized trials suggests that patients with higher LVEF show a risk reduction strictly related to overall cardiovascular (CV) events; on the other hand, patients experiencing lower LVEF values have a decrease in HF-related events. The current paper reports the main limitations and shortcomings in LVEF assessment, with specific focus on patients affected by HFpEF, and it suggests alternative measurements better reflecting the real hemodynamic status. Future investigations may elucidate whether the development of non-invasive stroke volume and longitudinal function measurements could be extensively applied in clinical trials for better phenotyping and screening of HFpEF patients.