[Secondary hypertension: diagnosis and treatment]. / Ipertensione arteriosa secondaria: diagnosi e trattamento.

Hypertension does not recognize obvious pathogenic causes in the majority of patients (essential hypertension). However, a secondary underlying cause of hypertension can be recognized in 5-10% of unselected hypertensive patients, and this prevalence may increase to more than 20% in patients with hypertension that is difficult to control or frankly resistant to treatment. In children, secondary hypertension is most often due to aortic coarctation, distal thoracic or abdominal aortic stenosis, or specific gene mutations. In adults or elderly individuals, secondary hypertension is most often due to atherosclerotic renal artery stenosis, primary hyperaldosteronism, and Cushing's disease or syndrome. Parenchymal nephropathy and hyperparathyroidism can cause hypertension at all ages, while pheochromocytoma and paraganglioma tend to occur more often in adolescents or young adults. In general, secondary hypertension should be suspected in subjects with: (a) onset of hypertension under 30 years of age especially if in the absence of hypertensive family history or other risk factors for hypertension; (b) treatment-resistant hypertension; c) severe hypertension (>180/110 mmHg), malignancy, or hypertensive emergencies; d) rapid rise in blood pressure values in previously well controlled patients. Any clinical signs suspicious or suggestive of hypertension from endocrine causes, a "reverse dipping" or "non-dipping'" profile at 24 h ambulatory blood pressure monitoring not justified by other factors, signs of obvious organ damage may be helpful clues for diagnosis. Finally, patients snoring or with clear sleep apnea should also be considered for possible secondary hypertension.

Rationale and design of ELIXIR, a randomized, controlled trial to evaluate efficacy and safety of XyloCore, a glucose-sparing solution for peritoneal dialysis.

Peritoneal dialysis adoption and technique survival is affected by limitations related to peritoneal membrane longevity and metabolic alterations. Indeed, almost all peritoneal dialysis fluids exploit glucose as an osmotic agent that rapidly diffuses across the peritoneal membrane, potentially resulting in metabolic abnormalities such as hyperglycemia, hyperinsulinemia, obesity, and hyperlipidemia. Moreover, glucose-degradation products generated during heat sterilization, other than glucose itself, induce significant morphological and functional changes in the peritoneum leading to ultrafiltration failure. The partial substitution of glucose with osmotic agents characterized by a better local and systemic biocompatibility has been suggested as a potential strategy to innovate peritoneal dialysis fluids. The approach aims to minimize glucose-associated toxicity, preserving the peritoneal membrane welfare and counteracting common comorbidities. In this work, we report the clinical trial design of ELIXIR, a phase III randomized, controlled, blinded outcome assessment study comparing Xylocore®, an innovative formulation based on Xylitol and l-carnitine, to standard glucose-based regimens, in end-stage kidney disease patients treated with continuous ambulatory peritoneal dialysis; 170 patients will be randomized (1:1) to receive XyloCore® or to continue their pre-randomization peritoneal dialysis (PD) therapy with glucose-only PD solutions, for 6 months. The primary study's objective is to demonstrate the noninferiority of XyloCore® in terms of Kt/V urea, for which a clinically acceptable noninferiority margin of -0.25 has been determined, assuming that all patients will be treated aiming to a minimum target of 1.7 and an optimal target of 2.0.

Risk of Cardiovascular Events in Metabolically Healthy Overweight or Obese Adults: Role of LDL-Cholesterol in the Stratification of Risk.

The objective of this study was to investigate the longitudinal association of metabolically healthy overweight/obese adults with major adverse cardiovascular events (MACE) and the effect of LDL-cholesterol levels on this association. This study was conducted with 15,904 participants from the URRAH study grouped according to BMI and metabolic status. Healthy metabolic status was identified with and without including LDL-cholesterol. The risk of MACE during 11.8 years of follow-up was evaluated with multivariable Cox regressions. Among the participants aged <70 years, high BMI was associated with an increased risk of MACE, whereas among the older subjects it was associated with lower risk. Compared to the group with normal weight/healthy metabolic status, the metabolically healthy participants aged <70 years who were overweight/obese had an increased risk of MACE with an adjusted hazard ratio of 3.81 (95% CI, 1.34-10.85, p = 0.012). However, when LDL-cholesterol < 130 mg/dL was included in the definition of healthy metabolic status, no increase in risk was found in the overweight/obese adults compared to the normal weight individuals (hazard ratio 0.70 (0.07-6.71, p = 0.75). The present data show that the risk of MACE is increased in metabolically healthy overweight/obese individuals identified according to standard criteria. However, when LDL-cholesterol is included in the definition, metabolically healthy individuals who are overweight/obese have no increase in risk.

Serum Uric Acid, Hypertriglyceridemia, and Carotid Plaques: A Sub-Analysis of the URic Acid Right for Heart Health (URRAH) Study.

High levels of serum uric acid (SUA) and triglycerides (TG) might promote high-cardiovascular-risk phenotypes, including subclinical atherosclerosis. An interaction between plaques xanthine oxidase (XO) expression, SUA, and HDL-C has been recently postulated. Subjects from the URic acid Right for heArt Health (URRAH) study with carotid ultrasound and without previous cardiovascular diseases (CVD) (n = 6209), followed over 20 years, were included in the analysis. Hypertriglyceridemia (hTG) was defined as TG ≥ 150 mg/dL. Higher levels of SUA (hSUA) were defined as ≥5.6 mg/dL in men and 5.1 mg/dL in women. A carotid plaque was identified in 1742 subjects (28%). SUA and TG predicted carotid plaque (HR 1.09 [1.04-1.27], p < 0.001 and HR 1.25 [1.09-1.45], p < 0.001) in the whole population, independently of age, sex, diabetes, systolic blood pressure, HDL and LDL cholesterol and treatment. Four different groups were identified (normal SUA and TG, hSUA and normal TG, normal SUA and hTG, hSUA and hTG). The prevalence of plaque was progressively greater in subjects with normal SUA and TG (23%), hSUA and normal TG (31%), normal SUA and hTG (34%), and hSUA and hTG (38%) (Chi-square, 0.0001). Logistic regression analysis showed that hSUA and normal TG [HR 1.159 (1.002 to 1.341); p = 0.001], normal SUA and hTG [HR 1.305 (1.057 to 1.611); p = 0.001], and the combination of hUA and hTG [HR 1.539 (1.274 to 1.859); p = 0.001] were associated with a higher risk of plaque. Our findings demonstrate that SUA is independently associated with the presence of carotid plaque and suggest that the combination of hyperuricemia and hypertriglyceridemia is a stronger determinant of carotid plaque than hSUA or hTG taken as single risk factors. The association between SUA and CVD events may be explained in part by a direct association of UA with carotid plaques.

Prognostic impact of hypertension grading.

BACKGROUND: Most Hypertension Guidelines grade hypertension according to various cut-off values. We sought to investigate the prognostic impact of Grades 1 (140-159 and/or 90-99 mmHg), 2 (160-179 and/or 100-109 mmHg) and 3 (≥180 and/or ≥110 mmHg). METHODS: We followed for an average of 10 years a cohort of 3,150 initially untreated hypertensive patients (mean age 50 years, 44 % women) with no previous cardiovascular disease at entry. All patients underwent diagnostic tests including 24-hour ambulatory blood pressure (BP) monitoring. RESULTS: At entry, average clinic BP was 156/97 mmHg and average 24-hour BP was 137/87 mmHg. During follow-up, 314 patients experienced a first major cardiovascular event (composite of non-fatal myocardial infarction or stroke, cardiovascular death, or hospitalization for heart failure). Event rate was not formally dissimilar between Grade 1 and Grade 2 (0.73 vs 0.95 per 100 patient-years, respectively; p = 0.06). It was higher in Grade 3 (1.93 per 100 patient-years; p < 0.01 vs Grade 1 and Grade 2). After adjustment for a robust set of covariables, the hazard ratio was not dissimilar between Grade 1 and Grade 2 (p = 0.27), and higher in Grade 3 than in Grade 1 (p < 0.01), but the excess risk in Grade 3 was no longer significant (hazard ratio: 1.25, 95 % CI 0.87-1.78; p = 0.22) after adjustment for 24-hour ambulatory systolic BP. CONCLUSIONS: We were unable to find a significant difference in the relative hazard of cardiovascular events tied to hypertension Grades 1 and 2. Conversely, Grade 3 (clinic BP ≥180/110 mmHg) portends a higher cardiovascular risk, which is associated with higher levels of 24-hour ambulatory BP.

Molecular Targets of Novel Therapeutics for Diabetic Kidney Disease: A New Era of Nephroprotection.

Diabetic kidney disease (DKD) is a chronic microvascular complication in patients with diabetes mellitus (DM) and the leading cause of end-stage kidney disease (ESKD). Although glomerulosclerosis, tubular injury and interstitial fibrosis are typical damages of DKD, the interplay of different processes (metabolic factors, oxidative stress, inflammatory pathway, fibrotic signaling, and hemodynamic mechanisms) appears to drive the onset and progression of DKD. A growing understanding of the pathogenetic mechanisms, and the development of new therapeutics, is opening the way for a new era of nephroprotection based on precision-medicine approaches. This review summarizes the therapeutic options linked to specific molecular mechanisms of DKD, including renin-angiotensin-aldosterone system blockers, SGLT2 inhibitors, mineralocorticoid receptor antagonists, glucagon-like peptide-1 receptor agonists, endothelin receptor antagonists, and aldosterone synthase inhibitors. In a new era of nephroprotection, these drugs, as pillars of personalized medicine, can improve renal outcomes and enhance the quality of life for individuals with DKD.

Managing hyperkalemia in patients with heart failure on guideline-directed medical therapy: challenges and opportunities.

Heart failure is a chronic and invalidating syndrome that affects tens of millions of people worldwide with significant socio-economic ramifications for the health care systems. Significant progress in the understanding of the pathophysiology of heart failure has allowed the gradual introduction of several drug classes for the management of such patients. Beta-blockers, mineralocorticoid receptor antagonists, angiotensin receptor neprilysin inhibitors, and sodium-glucose-cotransporter 2 inhibitors are all considered pillars of the guideline-directed medical therapy for heart failure. Despite remarkable improvements in the morbidity and mortality of heart failure, however, many patients still develop clinically significant hyperkalemia during combined treatment with those four pharmacological pillars. The consequence is often a down-titration or discontinuation of one or more crucial drugs, which in turns leads to a considerable increase in the risk of cardiovascular events, dialysis, and all-cause mortality. This paper will explore novel approaches for the management of hyperkalemia in heart failure, including closer monitoring of potassium levels, early review of drugs that might increase the risk of hyperkalemia, and pharmacological treatment of hyperkalemia, with a special emphasis on sodium-glucose-cotransporter 2 inhibitors and potassium-binding agents, including patiromer and sodium zirconium cyclosilicate.

[Non-inferiority trials]. / Gli studi di non-inferiorità.

Superiority trials are designed to test the hypothesis that a given diagnostic or therapeutic strategy is better than (i.e. "superior to") placebo or an active control. Conversely, non-inferiority trials test the hypothesis that a newer (i.e. alternative) strategy is not "unacceptably worse" than a control (i.e. "traditional", or "older") strategy. Non-inferiority trials are increasingly conducted in clinical medicine more often when a "newer" strategy is supposed to offer a relevant advantage in terms other than clinical efficacy (i.e. better tolerability, less cost, simpler regimen, etc.) versus a "gold standard" traditional strategy. The principle underlying non-inferiority trials is that the above advantage justifies the preferential use of the newer strategy in the clinical practice even if the clinical efficacy of the "new" appears to be a bit worse than that of the "old", albeit not unacceptably worse (i.e. not beyond a pre-specified value). The demonstration of non-inferiority requires that the confidence interval of the point estimate (e.g. the hazard ratio) does not cross a pre-specified limit. The definition of such pre-specified limit, the so called "non-inferiority margin", is a pivotal point when planning non-inferiority trials. It denotes the maximally tolerated worse effect of the alternative strategy, compared with the traditional one, required to conclude that an alternative strategy is non-inferior to the traditional "gold standard". The non-inferiority margin is derived from previous trials evaluating the efficacy of the traditional strategy vs placebo. We reviewed the principles and the practical aspects in the design and conduct of non-inferiority trials.

Serum Uric Acid/Serum Creatinine Ratio and Cardiovascular Mortality in Diabetic Individuals-The Uric Acid Right for Heart Health (URRAH) Project.

Several studies have detected a direct association between serum uric acid (SUA) and cardiovascular (CV) risk. In consideration that SUA largely depends on kidney function, some studies explored the role of the serum creatinine (sCr)-normalized SUA (SUA/sCr) ratio in different settings. Previously, the URRAH (URic acid Right for heArt Health) Study has identified a cut-off value of this index to predict CV mortality at 5.35 Units. Therefore, given that no SUA/sCr ratio threshold for CV risk has been identified for patients with diabetes, we aimed to assess the relationship between this index and CV mortality and to validate this threshold in the URRAH subpopulation with diabetes; the URRAH participants with diabetes were studied (n = 2230). The risk of CV mortality was evaluated by the Kaplan-Meier estimator and Cox multivariate analysis. During a median follow-up of 9.2 years, 380 CV deaths occurred. A non-linear inverse association between baseline SUA/sCr ratio and risk of CV mortality was detected. In the whole sample, SUA/sCr ratio > 5.35 Units was not a significant predictor of CV mortality in diabetic patients. However, after stratification by kidney function, values > 5.35 Units were associated with a significantly higher mortality rate only in normal kidney function, while, in participants with overt kidney dysfunction, values of SUA/sCr ratio > 7.50 Units were associated with higher CV mortality. The SUA/sCr ratio threshold, previously proposed by the URRAH Study Group, is predictive of an increased risk of CV mortality in people with diabetes and preserved kidney function. While, in consideration of the strong association among kidney function, SUA, and CV mortality, a different cut-point was detected for diabetics with impaired kidney function. These data highlight the different predictive roles of SUA (and its interaction with kidney function) in CV risk, pointing out the difference in metabolic- and kidney-dependent SUA levels also in diabetic individuals.

Triglyceride-glucose Index and Mortality in a Large Regional-based Italian Database (Urrah Project).

PURPOSE: Recently, a novel index (triglyceride-glucose index-TyG) was considered a surrogate marker of insulin resistance (IR); in addition, it was estimated to be a better expression of IR than widely used tools. Few and heterogeneous data are available on the relationship between this index and mortality risk in non-Asian populations. Therefore, we estimated the predictive role of baseline TyG on the incidence of all-cause and cardiovascular (CV) mortality in a large sample of the general population. Moreover, in consideration of the well-recognized role of serum uric acid (SUA) on CV risk and the close correlation between SUA and IR, we also evaluated the combined effect of TyG and SUA on mortality risk. METHODS: The analysis included 16,649 participants from the URRAH cohort. The risk of all-cause and CV mortality was evaluated by the Kaplan-Meier estimator and Cox multivariate analysis. RESULTS: During a median follow-up of 144 months, 2569 deaths occurred. We stratified the sample by the optimal cut-off point for all-cause (4.62) and CV mortality (4.53). In the multivariate Cox regression analyses, participants with TyG above cut-off had a significantly higher risk of all-cause and CV mortality, than those with TyG below the cut-off. Moreover, the simultaneous presence of high levels of TyG and SUA was associated with a higher mortality risk than none or only one of the two factors. CONCLUSIONS: The results of this study indicate that these TyG (a low-cost and simple non-invasive marker) thresholds are predictive of an increased risk of mortality in a large and homogeneous general population. In addition, these results show a synergic effect of TyG and SUA on the risk of mortality.

The lowest well tolerated blood pressure: A personalized target for all?

The optimal blood pressure (BP) target for prevention of cardiovascular complications of hypertension remains uncertain. Most Guidelines suggest different targets depending on age, comorbidities and treatment tolerability, but the underlying evidence is not strong. Results of randomized strategy trials comparing lower (i.e., more intensive) versus higher (i.e., less intensive) BP targets should drive the definition. However, these trials tested different BP targets based on systolic BP, diastolic BP or combined systolic and diastolic BP goals. Overall, the more intensive treatment targets reduced the risk of major cardiovascular complications of hypertension when compared with the less intensive targets, despite a higher incidence of unwanted effects including, but not limited to, hypotension, electrolyte abnormalities and renal dysfunction. Consequently, some Guidelines defined low BP thresholds (i.e., 120/70 mmHg) not to exceed downward because of the expectation that unwanted effects may outweigh the outcome benefits. The present review discusses the evidence underlying the choice of BP targets, which remains an important step in the management of hypertensive patients. We conclude that, on the ground of the heterogeneity of available data in support to fixed BP targets, their definition should be personalized in all patients and based on best trade-off between efficacy and safety, i.e., the lowest well tolerated BP.

Prognostic Value and Relative Cutoffs of Triglycerides Predicting Cardiovascular Outcome in a Large Regional-Based Italian Database.

BACKGROUND: Despite longstanding epidemiologic data on the association between increased serum triglycerides and cardiovascular events, the exact level at which risk begins to rise is unclear. The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension has conceived a protocol aimed at searching for the prognostic cutoff value of triglycerides in predicting cardiovascular events in a large regional-based Italian cohort. METHODS AND RESULTS: Among 14 189 subjects aged 18 to 95 years followed-up for 11.2 (5.3-13.2) years, the prognostic cutoff value of triglycerides, able to discriminate combined cardiovascular events, was identified by means of receiver operating characteristic curve. The conventional (150 mg/dL) and the prognostic cutoff values of triglycerides were used as independent predictors in separate multivariable Cox regression models adjusted for age, sex, body mass index, total and high-density lipoprotein cholesterol, serum uric acid, arterial hypertension, diabetes, chronic renal disease, smoking habit, and use of antihypertensive and lipid-lowering drugs. During 139 375 person-years of follow-up, 1601 participants experienced cardiovascular events. Receiver operating characteristic curve showed that 89 mg/dL (95% CI, 75.8-103.3, sensitivity 76.6, specificity 34.1, P<0.0001) was the prognostic cutoff value for cardiovascular events. Both cutoff values of triglycerides, the conventional and the newly identified, were accepted as multivariate predictors in separate Cox analyses, the hazard ratios being 1.211 (95% CI, 1.063-1.378, P=0.004) and 1.150 (95% CI, 1.021-1.295, P=0.02), respectively. CONCLUSIONS: Lower (89 mg/dL) than conventional (150 mg/dL) prognostic cutoff value of triglycerides for cardiovascular events does exist and is associated with increased cardiovascular risk in an Italian cohort.

Kidney Fibrosis and Oxidative Stress: From Molecular Pathways to New Pharmacological Opportunities.

Kidney fibrosis, diffused into the interstitium, vessels, and glomerulus, is the main pathologic feature associated with loss of renal function and chronic kidney disease (CKD). Fibrosis may be triggered in kidney diseases by different genetic and molecular insults. However, several studies have shown that fibrosis can be linked to oxidative stress and mitochondrial dysfunction in CKD. In this review, we will focus on three pathways that link oxidative stress and kidney fibrosis, namely: (i) hyperglycemia and mitochondrial energy imbalance, (ii) the mineralocorticoid signaling pathway, and (iii) the hypoxia-inducible factor (HIF) pathway. We selected these pathways because they are targeted by available medications capable of reducing kidney fibrosis, such as sodium-glucose cotransporter-2 (SGLT2) inhibitors, non-steroidal mineralocorticoid receptor antagonists (MRAs), and HIF-1alpha-prolyl hydroxylase inhibitors. These drugs have shown a reduction in oxidative stress in the kidney and a reduced collagen deposition across different CKD subtypes. However, there is still a long and winding road to a clear understanding of the anti-fibrotic effects of these compounds in humans, due to the inherent practical and ethical difficulties in obtaining sequential kidney biopsies and the lack of specific fibrosis biomarkers measurable in easily accessible matrices like urine. In this narrative review, we will describe these three pathways, their interconnections, and their link to and activity in oxidative stress and kidney fibrosis.

Anticoagulation in atrial fibrillation. A large real-world update.

INTRODUCTION: In a large nationwide administrative database including ∼35 % of Italian population, we analyzed the impact of oral anticoagulant treatment (OAT) in patients with a hospital diagnosis of non-valvular atrial fibrillation (NVAF). METHODS AND RESULTS: Of 170404 OAT-naïve patients (mean age 78.7 years; 49.4 % women), only 61.1 % were prescribed direct oral anticoagulants, DOACs, or vitamin-K antagonists, VKAs; 14.2 % were given aspirin (ASA), and 24.8 % no anti-thrombotic drugs (No Tx). We compared ischemic stroke (IS), IS and systemic embolism (IS/SE), intracranial hemorrhage (ICH), major bleeding (MB), major gastro-intestinal bleeding, all-cause deaths and the composite outcome, across four propensity-score matched treatment cohorts with >15400 patients each. Over 2.9±1.5 years, the incidence of IS and IS/SE was slightly less with VKAs than with DOACs (1.62 and 1.84 vs 1.81 and 1.99 events.100 person-years; HR=0.85, 95%CI=0.76-0.95 and HR=0.87, 95%CI=0.78-0.97). This difference disappeared in a sensitivity analysis which excluded those patients treated with low-dose of apixaban, edoxaban, or rivaroxaban (41.7% of DOACs cohort). Compared with DOACs, VKAs were associated with greater incidence of ICH (1.09 vs 0.81; HR=1.38, 95%CI=1.17-1.62), MB (3.78 vs 3.31; HR=1.14, 95%CI=1.02-1.28), all-cause mortality (9.66 vs 10.10; HR=1.07, 95%CI=1.02-1.11), and composite outcome (13.72 vs 13.32; HR=1.04, 95%CI=1.01-1.08). IS, IS/SE, and mortality were more frequent with ASA or No Tx than with VKAs or DOACs (p<0.001 for all comparisons). CONCLUSIONS: Beyond confirming the association with a better net clinical benefit of DOACs over VKAs, our findings substantiate the large proportion of NVAF patients still inappropriately anticoagulated, thereby reinforcing the need for educational programs.

The Results of the URRAH (Uric Acid Right for Heart Health) Project: A Focus on Hyperuricemia in Relation to Cardiovascular and Kidney Disease and its Role in Metabolic Dysregulation.

The relationship between Serum Uric Acid (UA) and Cardiovascular (CV) diseases has already been extensively evaluated, and it was found to be an independent predictor of all-cause and cardiovascular mortality but also acute coronary syndrome, stroke and heart failure. Similarly, also many papers have been published on the association between UA and kidney function, while less is known on the role of UA in metabolic derangement and, particularly, in metabolic syndrome. Despite the substantial number of publications on the topic, there are still some elements of doubt: (1) the better cut-off to be used to refine CV risk (also called CV cut-off); (2) the needing for a correction of UA values for kidney function; and (3) the better definition of its role in metabolic syndrome: is UA simply a marker, a bystander or a key pathological element of metabolic dysregulation?. The Uric acid Right for heArt Health (URRAH) project was designed by the Working Group on uric acid and CV risk of the Italian Society of Hypertension to answer the first question. After the first papers that individuates specific cut-off for different CV disease, subsequent articles have been published responding to the other relevant questions. This review will summarise most of the results obtained so far from the URRAH research project.

Use of Oral Anticoagulants in Patients with Atrial Fibrillation: Preliminary Data from the Italian Atrial Fibrillation (ITALY-AF) Registry.

BACKGROUND: Atrial fibrillation (AFIB), the most frequent cardiac arrhythmia, is a major risk factor for stroke, heart failure, and death. Because of the recent advances in AFIB management and the availability of new oral anticoagulants (OACs), there is a need for a systematic and predefined collection of contemporary data regarding its management and treatment. METHODS: The objective of the ongoing ITALY-AFIB registry is to evaluate the long-term morbidity and mortality in patients with AFIB and to verify the implementation of the current guidelines for stroke prevention in these patients. The registry includes consecutive in- and out-patients with first diagnosed, paroxysmal, persistent, or permanent AFIB. In patients in sinus rhythm at entry, the qualifying episode of AFIB, confirmed by ECG diagnosis, had to have occurred within 1 year before entry. The clinical record form is web-based and accessible by personal keyword. RESULTS: Enrolment into the registry started in the year 2013. In a current cohort of 2470 patients (mean age 75 ± 11 years, males 56%), the mean CHA2DS2-VASc score was 3.7 ± 1.8, and the mean HAS-BLED was 1.6 ± 0.9. There were no significant sex differences in the AFIB subtypes. At the end of the inclusion visit and after receiving knowledge of the web-based electronic estimate of risk for stroke and bleeding, the proportion of patients discharged with OACs was 80%. After exclusion of patients with first diagnosed AFIB (n = 397), the proportion of patients with prescription of OACs rose from 66% before the visit to 82% on discharge (p < 0.0001). Prescription of aspirin or other antiplatelet drugs fell from 18% before the visit to 10% on discharge (p < 0.0001). CONCLUSIONS: A web-based management of AFIB with automated estimation of risk profiles appears to favorably affect adherence to AFIB guidelines, based on a high proportion of patients treated with OACs and a substantial decline in the use of antiplatelet drugs.

Left ventricular remodeling response to SGLT2 inhibitors in heart failure: an updated meta-analysis of randomized controlled studies.

BACKGROUND: Randomized controlled trials (RCTs) reported contrasting results about reverse left ventricular remodeling (LVR) after sodium-glucose co-transporter-2 inhibitors (SGLT2i) therapy in patients with heart failure (HF). METHODS AND RESULTS: We performed a metanalysis of RCTs of SGLT2i administration in HF outpatients published until June 2022 searching four electronic databases. The protocol has been published in PROSPERO. Primary LVR outcome was change in absolute LV end-diastolic (LVEDV) and end-systolic volume (LVESV) from baseline to study endpoint. Secondary outcomes included changes in LVEDV and LVESV indexed to body surface area, LV Mass index (LVMi), LV ejection fraction (LVEF), and N-terminal pro-B-type natriuretic peptide (NTproBNP). Mean differences (MDs) with 95% CIs were pooled. A total of 9 RCTs (1385 patients) were analyzed. All of them reported data on LVEF. Six trials reported data on LVESV and LVEDV (n = 951); LVMi was available in 640. SGLT2i treatment significantly reduced LVEDV [MD= -10.59 ml (-17.27; -3.91), P = 0.0019], LVESV [MD= -8.80 ml (-16.91; -0.694), P = 0.0334], and LVMI [MD= -5.34 gr/m2 (-9.76; -0.922), P = 0.0178], while LVEF significantly increased [MD = + 1.98% (0.67; 0.306), P = 0.0031]. By subgroup analysis, the beneficial effects of SGLT2i on LVEF did not differ by imaging method used, time to follow-up re-evaluation, or HF phenotype. Reduction in LV volumes tended to be greater in HF with reduced EF (HFrEF) than in those with preserved EF (HFpEF), while the opposite was observed for LVMi. CONCLUSIONS: Treatment with SGLT2i significantly reversed cardiac volumes, improving LV systolic function and LV mass, particularly in HFrEF patients.

Worldwide impact of COVID-19 on hospital admissions for non-ST-elevation acute coronary syndromes (NSTACS): a systematic review with meta-analysis of 553,038 cases.

BACKGROUND: How COVID-19 impacted non-ST-segment elevation acute coronary syndromes (NSTACS) is object of controversial reports. AIM: To systematically review studies reporting NSTACS hospitalizations during COVID-19 pandemic, and analyze whether differences in COVID-19 epidemiology, methodology of report, or public health-related factors could contribute to discrepant findings. METHODS: Comprehensive search (MedLine, Embase, Scopus, Web-of-Science, Cochrane Register), of studies reporting NSTACS hospitalizations during COVID-19 pandemic compared with a reference period, following Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Data were independently extracted by multiple investigators and pooled using a random-effects model. Health-related metrics were from publicly available sources, and analyzed through multiple meta-regression modelling. RESULTS: We retrieved 102 articles (553 038 NSTACS cases, 40 countries). During peak COVID-19 pandemic, overall Incidence Rate-Ratio (IRR) of NSTACS hospitalizations over reference period decreased (0.70, 95% CI 0.66-0.75; p < 0.00001). Significant heterogeneity was detected among studies (I2= 98%; p < 0.00001). Importantly, wide variations were observed among, and within, countries. No significant differences were observed by study quality, whereas comparing different periods within 2020 resulted in greater decrease ((IRR: 0.61; CI: 0.53-0.71) than comparing 2020 vs previous years (IRR: 0.74; CI 0.69-0.79). Among many variables, major predictors of heterogeneity were: Sars-Cov-2 reproduction rate/country, number of hospitals queried, reference period length; country stringency index and socio-economical indicators did not significantly contribute. CONCLUSIONS: During COVID-19 pandemic NSTACS hospitalizations decreased significantly worldwide. However, substantial heterogeneity emerged among countries, and within the same country. Factors linked to public health management, but also to methodologies to collect results may have contributed to this heterogeneity. Trial registration: The protocol was registered in PROSPERO International Prospective Register of Systematic Reviews (ID: CRD42022308159).