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Hypertrophic cardiomyopathy is an important cause of heart failure and arrhythmias, including sudden death, with a major impact on the healthcare system. Genetic causes and different phenotypes are now increasingly being identified for this condition. In addition, specific medications, such as myosin inhibitors, have been recently shown as potentially able to modify its symptoms, hemodynamic abnormalities and clinical course. Our article aims to provide a comprehensive outline of the epidemiology, diagnosis and treatment of hypertrophic cardiomyopathy in the current era., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Italian Federation of Cardiology.)

Aortic stenosis is the most prevalent valvular heart disease requiring intervention, especially in the elderly population. Surgical aortic valve replacement and transcatheter aortic valve implantation (TAVI) are well established treatment options for symptomatic patients with severe aortic stenosis, as they provide a significant survival benefit. Aortic stenosis may have an important impact on patients' quality of life (QoL). However, advanced age, comorbidities and frailty may limit the beneficial effect of aortic stenosis interventions in terms of QoL. Current guidelines mention the importance of frailty and avoiding the futility of interventions, but lack specific indications about decision-making. Also, there are limited data on how to specifically assess QoL in aortic stenosis patients since the most used questionnaires are validated in different populations (i.e. heart failure). The aim of this review is to summarize all the available tools for QoL assessment in patients with aortic stenosis; to report current evidence on the impact of TAVI on QoL; and to discuss the role of frailty and comorbidities in this setting., (Copyright © 2024 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Aims: To evaluate the role of tricuspid regurgitation in advanced heart failure., Methods: The multicenter observational HELP-HF registry enrolled consecutive patients with heart failure and at least one 'I NEED HELP' criterion evaluated at four Italian centers between January 2020 and November 2021. Patients with no data on tricuspid regurgitation and/or receiving tricuspid valve intervention during follow-up were excluded. The population was stratified by no/mild tricuspid regurgitation vs. moderate tricuspid regurgitation vs. severe tricuspid regurgitation. Variables independently associated with tricuspid regurgitation, as well as the association between tricuspid regurgitation and clinical outcomes were investigated. The primary outcome was all-cause mortality., Results: Among the 1085 patients included in this study, 508 (46.8%) had no/mild tricuspid regurgitation, 373 (34.4%) had moderate tricuspid regurgitation and 204 (18.8%) had severe tricuspid regurgitation. History of atrial fibrillation, any prior valve surgery, high dose of furosemide, preserved left ventricular ejection fraction, moderate/severe mitral regurgitation and pulmonary hypertension were found to be independently associated with an increased likelihood of severe tricuspid regurgitation. Estimated rates of 1-year all-cause death were of 21.4, 24.5 and 37.1% in no/mild tricuspid regurgitation, moderate tricuspid regurgitation and severe tricuspid regurgitation, respectively (log-rank P  < 0.001). As compared with nonsevere tricuspid regurgitation, severe tricuspid regurgitation was independently associated with a higher risk of all-cause mortality (adjusted hazard ratio 1.38, 95% confidence interval 1.01-1.88, P  = 0.042), whereas moderate tricuspid regurgitation did not., Conclusion: In a contemporary, real-world cohort of patients with advanced heart failure, several clinical and echocardiographic characteristics are associated with an increased likelihood of severe tricuspid regurgitation. Patients with severe tricuspid regurgitation have an increased risk of mortality., (Copyright © 2024 Italian Federation of Cardiology - I.F.C. All rights reserved.)

In the latest ESC/EACTS Guidelines for the Management of Valvular Heart Disease, right ventricular dilatation and dysfunction, severe pulmonary hypertension and tricuspid annulus dilatation were reported to be the most important parameters to consider in patient selection for tricuspid valve interventions. Indeed, comprehensive right ventricular assessment is crucial in patients with severe tricuspid regurgitation who may benefit from transcatheter or surgical procedures. However, the only guideline parameter considered for intervention has been tricuspid annular dilatation in the presence of at least mild to moderate tricuspid regurgitation, with no other right ventricular markers used in the decision-making process for invasive treatment. Notably, challenges in the assessment of right ventricular function may limit establishing thresholds for defining right ventricular dysfunction. The aim of this review is to summarize current evidence on the prognostic significance of right ventricular function in patients with tricuspid regurgitation undergoing percutaneous or surgical interventions., (Copyright © 2023 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Background: Hospitalization is associated with poor outcomes in patients with heart failure, but its prognostic role in advanced heart failure is still unsettled. We evaluated the prognostic role of heart failure hospitalization in patients with advanced heart failure., Methods: The multicenter HELP-HF registry enrolled consecutive patients with heart failure and at least one high-risk 'I NEED HELP' marker. Characteristics and outcomes were compared between patients who were hospitalized for decompensated heart failure (inpatients) or not (outpatients) at the time of enrolment. The primary endpoint was the composite of all-cause mortality or first heart failure hospitalization., Results: Among the 1149 patients included [mean age 75.1 ± 11.5 years, 67.3% men, median left ventricular ejection fraction (LVEF) 35% (IQR 25-50%)], 777 (67.6%) were inpatients at the time of enrolment. As compared with outpatients, inpatients had lower LVEF, higher natriuretic peptides and a worse clinical profile. The 1-year rate of the primary endpoint was 50.9% in inpatients versus 36.8% in outpatients [crude hazard ratio 1.70, 95% confidence interval (CI) 1.39-2.07, P < 0.001]. At multivariable analysis, inpatient status was independently associated with a higher risk of the primary endpoint (adjusted hazard ratio 1.54, 95% CI 1.23-1.93, P < 0.001). Among inpatients, the independent predictors of the primary endpoint were older age, lower SBP, heart failure association criteria for advanced heart failure and glomerular filtration rate 30 ml/min/1.73 m2 or less., Conclusion: Hospitalization for heart failure in patients with at least one high-risk 'I NEED HELP' marker is associated with an extremely poor prognosis supporting the need for specific interventions, such as mechanical circulatory support or heart transplantation., (Copyright © 2023 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Abstract: During the Coronavirus Disease 2019 (COVID-19) pandemic, the epidemiology of heart failure significantly changed with reduced access to health system resources and a worsening of patients' outcome. Understanding the causes of these phenomena could be important to refine the management of heart failure during and after the pandemic. Telemedicine was associated with an improvement in heart failure outcomes in several studies; therefore, it may help in refining the out-of-hospital care of heart failure. In this review, the authors describe the changes in heart failure epidemiology during the COVID-19 pandemic; analyse available evidence on use and benefit of telemedicine during the pandemic and prepandemic periods; and discuss approaches to optimize the home-based or outpatient heart failure management in the future, beyond the pandemic., (Copyright © 2023 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Aims: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been evaluated in phase 3 randomized-controlled trials (RCTs) that enrolled individuals with heart failure and preserved ejection fraction (HFpEF) based on detailed clinical, biochemical, and echocardiographic criteria (hereafter HF-RCTs), and in cardiovascular outcomes trials (CVOTs) in diabetic patients, in which the diagnosis of HFpEF relied on medical history., Methods and Results: We performed a study-level meta-analysis of the efficacy of SGLT2i across different definitions of HFpEF. Three HF-RCTs (EMPEROR-Preserved, DELIVER, and SOLOIST-WHF) and four CVOTs (EMPA-REG OUTCOME, DECLARE-TIMI 58, VERTIS-CV, and SCORED) were included, for a total of 14 034 patients. SGLT2i reduced the risk of cardiovascular death or heart failure hospitalization (HFH) in all RCTs pooled together [risk ratio 0.75, 95% confidence interval (95% CI) 0.63-0.89, NNT 19], in HF-RCTs (risk ratio 0.71, 95% CI 0.52-0.97, NNT 13), and in CVOTs (risk ratio 0.78, 95% CI 0.60-0.99, NNT 26). SGLT2i also decreased the risk of HFH in all RCTs (risk ratio 0.81, 95% CI 0.73-0.90, NNT 45), in HF-RCTs (risk ratio 0.81, 95% CI 0.72-0.93, NNT 37), and in CVOTs (risk ratio 0.78, 95% CI 0.61-0.99, NNT 46). By contrast, SGLT2i were not superior to placebo for cardiovascular death or all-cause death in all RCTs, HF-RCTs, or CVOTs. Results were comparable after excluding one RCT at a time. Meta-regression analysis confirmed that the type of RCT (HF-RCT vs. CVOT) did not influence the SGLT2i effect., Conclusions: In RCTs, SGLT2i improved the outcomes of patients with HFpEF regardless of how the latter was diagnosed., (Copyright © 2023 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Background: The role of TAPSE/PASP, a measurement of right ventricular to pulmonary artery coupling, in patients hospitalized for acute heart failure (AHF) is poorly described., Objectives: To evaluate the prognostic impact of TAPSE/PASP in AHF., Methods: This retrospective single-center study included patients hospitalized for AHF between January 2004 and May 2017. TAPSE/PASP was evaluated as a continuous variable and as tertiles according to its value on admission. The main outcome was the composite of 1-year all-cause death or heart failure hospitalization., Results: A total of 340 patients were included [mean age 68.8 ± 11.8 years; 76.2% men, mean left ventricular ejection fraction (LVEF) 30.4 ± 13.3%]. Patients with lower TAPSE/PASP had more comorbidities and a more advanced clinical profile, and received higher doses of intravenous furosemide in the first 24 h. There was a significant, linear, inverse relationship between TAPSE/PASP values and the incidence of the main outcome (P = 0.003). In two multivariable analyses including clinical (model 1), biochemical and imaging parameters (model 2) TAPSE/PASP ratio was independently associated with the primary end point [model 1: hazard ratio 0.813, 95% confidence interval (CI) 0.708-0.932, P = 0.003; model 2: hazard ratio 0.879, 95% CI 0.775-0.996, P = 0.043]. Patients with TAPSE/PASP greater than 0.47 mm/mmHg had a significantly lower risk of the primary end point (model 1: hazard ratio 0.473, 95% CI 0.277-0.808, P = 0.006; model 2: hazard ratio 0.582, 95% CI 0.355-0.955, P = 0.032; both compared with TAPSE/PASP <0.34 mm/mmHg). Similar findings were observed for 1-year all-cause mortality., Conclusion: TAPSE/PASP on admission demonstrated a prognostic value among patients with AHF., (Copyright © 2023 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Device-related thrombus (DRT) is a known complication occurring in up to 7% of patients undergoing percutaneous left atrial appendage closure (LAAC). Since the target population of LAAC is generally ineligible for oral anticoagulant therapies, DRT raises important concerns. The aim of this review will be to summarize available evidence on DRT after LAAC focusing on its possible impact on outcomes. Recent findings showed a tighter association between DRT and neurological ischemic events. Antithrombotic regimen adopted after LAAC may have a protective effect against DRT. Many patient-related and procedural factors have been identified as possible predictors of DRT. A tailored approach, which takes into account DRT, is needed in the patient selection for LAAC and in the postprocedural follow-up., (Copyright © 2022 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Prevalence of heart failure is increasing worldwide mainly due to the ageing of the population and the improvement in diagnosis and treatment. In recent years, huge progress has been made in the management of heart failure patients. A new definition of chronic heart failure based on left ventricular ejection fraction and its possible trajectories has been reported. New drug classes have been introduced for the treatment of chronic heart failure. In particular, the prognostic benefit of sodium glucose co-transporter 2 inhibitors was demonstrated across all the heart failure phenotypes. Therapies for patients with advanced heart failure (long-term mechanical circulatory supports and heart transplantation) are now indicated also in the case of mild-to-moderate symptoms but with high risk of progression. In patients with acute heart failure, monitoring of urinary sodium and the use of acetazolamide may lead to better decongestion. Importantly, pre- and postdischarge assessment should lead to optimal treatment. Devices and telemonitoring can also be of help. Cardiovascular and noncardiovascular comorbidities are major determinants of the clinical course and need proper management. This review will summarize these important advances., (Copyright © 2022 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Aims: To investigate the impact of the right ventricle to pulmonary artery (RV-PA) coupling on the outcome of patients undergoing transcatheter aortic valve intervention (TAVI), and to describe changes in right ventricular function, pulmonary hypertension, and their ratio after TAVI., Methods: Three hundred and seventy-seven patients from the Italian ClinicalService Project, who underwent TAVI between February 2011 and August 2020, were included. Tricuspid annular plane systolic excursion/pulmonary artery systolic pressure (TAPSE/PASP) ratio was retrospectively calculated as a surrogate of RV-PA coupling. The population was stratified according to TAPSE/PASP using a cut-off of 0.36 mm/mmHg derived from a receiving operating characteristic (ROC) curve. The primary end point was 6-month all-cause death., Results: Compared with patients with a TAPSE/PASP ratio ≥0.36 mm/mmHg (81%), those with TAPSE/PASP ratio <0.36 mm/mmHg (19%) had more comorbidities and were more symptomatic.Moreover, they were more likely to receive general anesthesia and an old generation device. Device success was similar between the two groups. A TAPSE/PASP ratio <0.36 mm/mmHg was associated with a higher risk of all-cause death at 6-months (17.3% versus 5.3%; adjusted HR 2.66; P = 0.041). The prognostic impact of the TAPSE/PASP ratio was stronger than the impact of TAPSE and PASP as separate parameters and was independent of the surgical risk score. Both TAPSE, PASP, and their ratio improved from baseline to 1 month and 6 months after TAVI., Conclusions: A TAPSE/PASP ratio <0.36 mm/mmHg is strongly associated with an increased risk of mortality after TAVI. Providing a left ventricle unloading, TAVI is associated with improvement of both TAPSE, PASP, and their ratio., (Copyright © 2022 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Background: Several risk factors have been identified to predict worse outcomes in patients affected by SARS-CoV-2 infection. Machine learning algorithms represent a novel approach to identifying a prediction model with a good discriminatory capacity to be easily used in clinical practice. The aim of this study was to obtain a risk score for in-hospital mortality in patients with coronavirus disease infection (COVID-19) based on a limited number of features collected at hospital admission., Methods and Results: We studied an Italian cohort of consecutive adult Caucasian patients with laboratory-confirmed COVID-19 who were hospitalized in 13 cardiology units during Spring 2020. The Lasso procedure was used to select the most relevant covariates. The dataset was randomly divided into a training set containing 80% of the data, used for estimating the model, and a test set with the remaining 20%. A Random Forest modeled in-hospital mortality with the selected set of covariates: its accuracy was measured by means of the ROC curve, obtaining AUC, sensitivity, specificity and related 95% confidence interval (CI). This model was then compared with the one obtained by the Gradient Boosting Machine (GBM) and with logistic regression. Finally, to understand if each model has the same performance in the training and test set, the two AUCs were compared using the DeLong's test. Among 701 patients enrolled (mean age 67.2 ± 13.2 years, 69.5% male individuals), 165 (23.5%) died during a median hospitalization of 15 (IQR, 9-24) days. Variables selected by the Lasso procedure were: age, oxygen saturation, PaO2/FiO2, creatinine clearance and elevated troponin. Compared with those who survived, deceased patients were older, had a lower blood oxygenation, lower creatinine clearance levels and higher prevalence of elevated troponin (all P < 0.001). The best performance out of the samples was provided by Random Forest with an AUC of 0.78 (95% CI: 0.68-0.88) and a sensitivity of 0.88 (95% CI: 0.58-1.00). Moreover, Random Forest was the unique model that provided similar performance in sample and out of sample (DeLong test P = 0.78)., Conclusion: In a large COVID-19 population, we showed that a customizable machine learning-based score derived from clinical variables is feasible and effective for the prediction of in-hospital mortality., (Copyright © 2022 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Introduction: The role of sex compared to comorbidities and other prognostic variables in patients with coronavirus disease (COVID-19) is unclear., Methods: This is a retrospective observational study on patients with COVID-19 infection, referred to 13 cardiology units. The primary objective was to assess the difference in risk of death between the sexes. The secondary objective was to explore sex-based heterogeneity in the association between demographic, clinical and laboratory variables, and patients' risk of death., Results: Seven hundred and one patients were included: 214 (30.5%) women and 487 (69.5%) men. During a median follow-up of 15 days, deaths occurred in 39 (18.2%) women and 126 (25.9%) men. In a multivariable Cox regression model, men had a nonsignificantly higher risk of death vs. women (P = 0.07).The risk of death was more than double in men with a low lymphocytes count as compared with men with a high lymphocytes count [overall survival hazard ratio (OS-HR) 2.56, 95% confidence interval (CI) 1.72-3.81]. In contrast, lymphocytes count was not related to death in women (P = 0.03).Platelets count was associated with better outcome in men (OS-HR for increase of 50 × 103 units: 0.88 95% CI 0.78-1.00) but not in women. The strength of association between higher PaO2/FiO2 ratio and lower risk of death was larger in women (OS-HR for increase of 50 mmHg/%: 0.72, 95% CI 0.59-0.89) vs. men (OS-HR: 0.88, 95% CI 0.80-0.98; P = 0.05)., Conclusions: Patients' sex is a relevant variable that should be taken into account when evaluating risk of death from COVID-19. There is a sex-based heterogeneity in the association between baseline variables and patients' risk of death., (Copyright © 2022 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Patients discharged after an episode of acute heart failure have an increased risk of hospitalizations and deaths within the subsequent 3 months. This phase is commonly called the 'vulnerable period' and it represents a window of opportunity of intervention in order to improve longer term outcomes. Prompt identification of signs of residual haemodynamic congestion is a priority in planning for the out-of-hospital management strategies. Patients will also need to be screened for frailty and have a prioritization of the management of their comorbidities. Life-saving medications should be started together or in a short time and up-titrated (when needed) according to blood pressure, heart rate and concomitant comorbidities. Ideally, patients should be assessed by their general practitioner within 1 week of discharge and have a hospital/clinic follow-up within 4 weeks of discharge. Patients should progressively resume physical activities and adhere to an educational programme with appropriate lifestyle adjustments best implemented during a cardiac rehabilitation programme., (Copyright © 2021 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Aims: Controversial data have been published regarding the prognostic role of cardiac troponins in patients who need hospitalization because of coronavirus disease 2019 (COVID-19). The aim of the study was to assess the role of high-sensitivity troponin plasma levels and of respiratory function at admission on all-cause deaths in unselected patients hospitalized because of COVID-19., Methods: We pooled individual patient data from observational studies that assessed all-cause mortality of unselected patients hospitalized for COVID-19. The individual data of 722 patients were included. The ratio of partial pressure arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) and high-sensitivity troponins was reported at admission in all patients. This meta-analysis was registered on PROSPERO (CRD42020213209)., Results: After a median follow-up of 14 days, 180 deaths were observed. At multivariable regression analysis, age [hazard ratio (HR) 1.083, 95% confidence interval (CI) 1.061-1.105, P < 0.0001], male sex (HR 2.049, 95% CI 1.319-3.184, P = 0.0014), moderate-severe renal dysfunction (estimated glomerular filtration rate  < 30 mL/min/m2) (HR 2.108, 95% CI 1.237-3.594, P = 0.0061) and lower PaO2/FiO2 (HR 0.901, 95% CI 0.829-0.978, P = 0.0133) were the independent predictors of death. A linear increase in the HR was associated with decreasing values of PaO2/FiO2 below the normality threshold. On the contrary, the HR curve for troponin plasma levels was near-flat with large CI for values above the normality thresholds., Conclusion: In unselected patients hospitalized for COVID-19, mortality is mainly driven by male gender, older age and respiratory failure. Elevated plasma levels of high-sensitivity troponins are not an independent predictor of worse survival when respiratory function is accounted for., (Copyright © 2021 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Background: Venous thromboembolism is the second leading cause of death in cancer patients and its incidence seems underestimated. In addition, cancer patients have an increased risk of developing atrial fibrillation, which may be the first presentation of cancer itself. The primary aim of this study was to define the incidence of venous thromboembolism (VTE) and atrial fibrillation in a real-word series of advanced cancer patients., Methods: We performed a retrospective single-institution study on patients diagnosed with stage IV solid neoplasia at the outpatient clinic of the Medical Oncology Unit (Spedali Civili Brescia, Italy), from January to December 2018., Results: A total of 403 patients were enrolled, with a mean age at presentation of 63 years (range 18-85 years). A VTE was observed in 24% of cases, half of which occurred after diagnosis of metastatic neoplasia, with a median time of onset of 5.5 months (range 0-84). About 3% of patients developed atrial fibrillation after cancer diagnosis. In this patient series, no statistically significant differences were found when comparing Khorana and PROTECHT thromboembolic risk scores, both before and after the start of chemotherapy. Overall, about 25% of the patients received anticoagulant therapy; in most cases, the drug of choice was low-molecular-weight heparin (LMWH)., Conclusion: This study showed for cancer patients a considerably higher incidence of VTE and a comparable incidence of atrial fibrillation than reported in literature. Validated thromboembolic risk scores appear to be poorly predictive, and LMWH remains the most widely used anticoagulant drug., (Copyright © 2020 Italian Federation of Cardiology - I.F.C. All rights reserved.)

: Tricuspid regurgitation, either isolated or associated with left-valve disease, has a strong impact on outcome. Surgical treatment of tricuspid regurgitation has increased in recent years, but in-hospital mortality remains high probably due to the risk profile of the recipients. As a consequence, most of the patients with severe tricuspid regurgitation, especially if isolated, remain untreated. Transcatheter tricuspid valve interventions are rapidly spreading as alternative options to open-heart procedures fulfilling this important unmet need. Although patient selection and timing of intervention are unclear, many devices have been developed in recent years for both repair and replacement of tricuspid valve. Repair tools can be targeted to leaflets or annulus. Replacement devices include heterotopic and orthotropic systems. The aim of this review is to report possible indications and summarize current data about the different devices available for transcatheter tricuspid valve interventions.

Aims: The aim of this study was to report the prevalence, clinical features and outcomes of patients with ST-elevation myocardial infarction (STEMI) hospitalized during the Corona-Virus Disease 2019 (COVID-19) outbreak compared with those admitted in a previous equivalent period., Methods and Results: Eighty-five patients admitted for STEMI at a high-volume Italian centre were included. Patients hospitalized during the COVID-19 outbreak (21 February-10 April 2020) (40%) were compared with those admitted in pre-COVID-19 period (3 January-20 February 2020) (60%). A 43% reduction in STEMI admissions was observed during the COVID-19 outbreak compared with the previous period. Time from symptom onset to first medical contact (FMC) and time from FMC to primary percutaneous coronary intervention (PPCI) were longer in patients admitted during the COVID-19 period compared with before [148 (79-781) versus 130 (30-185) min; P = 0.018, and 75 (59-148)] versus 45 (30-70) min; P < 0.001]. High-sensitive troponin T levels on admission were also higher. In-hospital mortality was 12% in the COVID-19 phase versus 6% in the pre-COVID-19 period. Incidence of the composite end-point, including free-wall rupture, severe left ventricular dysfunction, left ventricular aneurysm, severe mitral regurgitation and pericardial effusion, was higher during the COVID-19 than the pre-COVID-19 period (19.6 versus 41.2%; P = 0.030; odds ratio = 2.87; 95% confidence interval 1.09-7.58)., Conclusion: The COVID-19 pandemic had a significant impact on the STEMI care system reducing hospital admissions and prolonging revascularization time. This translated into a worse patient prognosis due to more STEMI complications.

: The coronavirus disease 2019 (COVID-19) has important implications for the cardiovascular care of patients. COVID-19 interacts with the cardiovascular system on multiple levels, increasing morbidity in patients with underlying cardiovascular conditions and favoring acute myocardial injury and dysfunction. COVID-19 infection may also have long-term implications for overall cardiovascular health. Many issues regarding the involvement of the cardiovascular system remain controversial. Despite angiotensin-converting enzyme 2 serving as the site of entry of the virus into the cells, the role of angiotensin-converting enzyme inhibitors or AT1 blockers requires further investigation. Therapies under investigation for COVID-19 may have cardiovascular side effects. Treatment of COVID-19, especially the use of antivirals, must be closely monitored. This article is a review of the most updated literature.

Aim: Adherence to guidelines was not homogeneous in Europe, according to the survey on cardiac resynchronization therapy conducted in 2008-2009. The aim of our study was to compare the results in the Italian and European cohorts of the Second European Cardiac Resynchronization Therapy Survey., Methods: Patients' characteristics, procedural data and follow-up were collected. Italian records were compared with European countries., Results: Italian hospitals enrolled 526 patients. The italian cohort was older (71.6 ± 9.5 vs. 68.4 ± 10.8; P < 0.00001), had less severe NYHA class (>II 47.2 vs. 59.6%; P < 0.00001), higher ejection fraction (30.3 ± 7.4 vs. 28.4 ± 8.2%; P < 0.00001), and less atrial fibrillation prevalence (34.4 vs. 41.2%; P = 0.00197) than the European cohort. Italian patients were more frequently hospitalized for heart failure in the previous year (51.9 vs. 46.2%; P = 0.01118) and had lower mean QRS duration (151 ± 26 vs. 157 ± 27 ms; P < 0.0001). CRT-D were more often implanted in Italian patients (79.3 vs. 69.3%; P < 0.00001). The complication rate was similar (4.6% vs. 5.6%; ns). The rate of use of ACEi/ARBs in Italy was lower than in Europe (77.2 vs. 86.9%; P < 0.00001). Patients were followed up in the implantation centre (92.1 vs. 86%; P = 0.00014), but rarely with remote monitoring (25.9 vs. 30%; P = 0.04792)., Conclusion: The survey demonstrates important similarities as well as substantial differences regarding most of the aspects evaluated. Efforts to implement adherence to guidelines will be endorsed in Italy.

: Despite recent improvement in therapy, heart failure with reduced ejection fraction (HFrEF) remains a major cause of increased mortality and morbidity.We have reviewed recent advances in the medical treatment of the patients with HFrEF, including drugs introduced into clinical practice for the first time in the most recent guidelines and drugs undergoing active clinical research in major randomized trials. Sacubitril/valsartan for HFrEF treatment, empagliflozin for heart failure prevention in diabetic patients, ferric carboxymaltose for iron deficiency and potassium binders for hyperkalaemia belong to the first category, whereas drugs undergoing phase 3 clinical trials include omecamtiv mecarbil and vericiguat. A large trial with rivaroxaban has been recently concluded.In conclusion, new drugs recently introduced for HFrEF treatment need implementation in clinical practice, as well as further studies to possibly expand their indications. Ongoing trials will show the role of new drugs acting on cardiac and vascular function and new mechanisms potentially involved in HFrEF progression.

Aims: The aim of this study was to evaluate the safety and efficacy of the EkoSonic Endovascular System (EKOS) in patients with acute pulmonary embolism (APE) at high or intermediate-high risk and contraindication to systemic fibrinolysis., Methods: This is a retrospective study including consecutive patients admitted due to high-risk or intermediate-high-risk APE and treated by EKOS because of an absolute or relative contraindication to systemic fibrinolysis. The primary efficacy end-point was the change from baseline to 72 h in right to left ventricular dimension ratio [right ventricular/left ventricular (RV/LV) ratio]; pulmonary embolic burden using the Qanadli Index; and systolic pulmonary arterial pressure (SPAP). The primary safety end-point was the occurrence of bleeding (GUSTO classification) within 72 h., Results: Eighteen patients (5 men, 13 women; mean age 74 ± 12.7 years) affected by high-risk APE (n = 5; 27.8%) or intermediate-high-risk APE (n = 13; 72.2%) were included. A significant reduction of mean RV/LV ratio (1.38 ± 0.3 vs. 0.97 ± 0.16; P < 0.0005); Qanadli Index [27.06 ± 2.6 vs. 18.8 ± 7.8 (P < 0.001) and SPAP (71.1 ± 12 vs. 45.2 ± 16 mmHg; P < 0.001)] was observed within 72 h after EKOS. Five bleeding events occurred: one fatal and four moderates; three out of them led to the access site hematoma, two due to pre-existing active bleeding., Conclusion: EKOS is an effective tool to treat patients with APE at high or intermediate-high risk and contraindication to fibrinolysis. It is a relatively safe therapy considering the critical conditions and high bleeding risk of the receiving population.

: Due to aging of the patients with heart failure, comorbidities are an emerging problem and, among them, iron deficiency is an important therapeutic target, independently of concomitant hemoglobin level. Iron deficiency affects up to 50% of heart failure patients, and it has been largely established its association with poor quality of life, impaired exercise tolerance and higher mortality. Randomized controlled trials (RCTs) and meta-analyses have demonstrated that intravenous iron supplementation in heart failure patients with iron deficiency positively affects symptoms, quality of life, exercise tolerance (as measured by VO2 peak and 6MWT), with a global trend to reduction of hospitalization rates. Current European Society of Cardiology Guidelines for heart failure recommend a diagnostic work-up for iron deficiency in all heart failure patients and intravenous iron supplementation with ferric carboxymaltose for symptomatic patients with iron deficiency, defined by ferritin level less than 100 μg/l or by ferritin 100-300 μg/l with TSAT less than 20%. On-going studies will provide new evidence for a better treatment of this important comorbidity of heart failure patients.

: The Prospective Comparison of Angiotensin Receptor Antagonist and Neprilysin Inhibitor with Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial (PARADIGM-HF) has shown a reduction in the risk of death and heart failure hospitalizations with sacubitril/valsartan, compared with enalapril, in patients with heart failure and reduced ejection fraction. Guidelines now recommend the substitution of angiotensin-converting enzyme inhibitors or AT1 blockers with sacubitril/valsartan in patients with heart failure and reduced ejection fraction. The aim of this review is to discuss factors that may have an impact on the implementation of these guidelines into clinical practice. The main limitation is that, based on the inclusion criteria of PARADIGM-HF, sacubitril/valsartan is not indicated in patients with heart failure and preserved ejection fraction, although they may be the majority of the patients with heart failure. The trial enrolled ambulatory patients and thus start of sacubitril/valsartan is not indicated in those hospitalized for heart failure. A drug's tolerability may be limited by hypotension with, however, a lower rate of renal dysfunction, compared with enalapril. The cost of the new treatment is also an issue. Similarly to what occurred when other neurohormonal antagonists have been introduced in clinical practice, increased awareness of poor heart failure outcomes and better patients' management programs may be of utmost importance for the implementation of this new agent.

: Despite recent advances in chronic heart failure treatment, prognosis of acute heart failure patients remains poor with a heart failure rehospitalization rate or death reaching approximately 25% during the first 6 months after discharge. In addition, about half of these patients have preserved ejection fraction for which there are no evidence-based therapies. Disappointing results from heart failure clinical trials over the past 20 years emphasize the need for developing novel approaches and pathways for testing new heart failure drugs and devices. Indeed, many trials are being conducted without matching the mechanism and action of the drug with the clinical event. The implementation of these novel approaches should be coupled with the training of a new generation of heart failure physicians and scientists in the art and science of clinical trials. Currently, drug development is led by opinion leaders and experts who, despite their huge personal experience, were never trained systematically on drug development. The aim of this article is to propose a training program of 'drug development in Heart Failure'. A physician attending this course would have to be trained with a major emphasis on heart failure pathophysiology to better match mechanisms of death and rehospitalization with mechanism of action of the drug. Applicants will have to prove their qualifications and special interest in heart failure drug development before enrollment. This article should serve as a roadmap on how to apply emerging general principles in an innovative drug-development-in-heart-failure-process as well as the introduction of a new educational and mentorship program focusing on younger generations of researchers.

Background: Low relative lymphocyte count is an important prognostic marker in acute heart failure (AHF); however, it could be influenced by other abnormalities in white cells count. Our purpose is to evaluate if low absolute lymphocyte count (ALC) is an independent predictor of events in patients with AHF., Methods: In a retrospective analysis, we included 309 patients with AHF, divided into two groups according to the median value of ALC at admission (1410 cells/μl). The primary end point was all-cause mortality or urgent heart transplantation within 1 year., Results: Patients with low ALC were older and had more comorbidity, namely atrial fibrillation, chronic kidney disease, chronic obstructive pulmonary disease and anemia. Low ALC was associated with higher all-cause mortality or urgent heart transplantation at 1 year (24.3 vs 13.0%; P = 0.012). In a multivariable model, the independent predictors of mortality at 1 year were ALC 1410 cells/μl or less at admission [hazard ratio 2.04; CI (confidence interval) 95% (1.06-3.95); P = 0.033], age [hazard ratio 1.08; CI 95% (1.04-1.12); P < 0.001], baseline serum creatinine [hazard ratio 1.25; CI 95% (1.05-1.50); P = 0.012] and baseline serum Na [hazard ratio 0.91; CI 95% (0.85-0.98); P = 0.013]., Conclusion: Low ALC in patients with AHF is associated with higher in-hospital mortality during the hospitalization and is an independent predictor of long-term mortality.

Aims: Obstructive sleep apnoea-hypopnoea (OSAH) is a prevalent condition characterized by repetitive pharyngeal collapse during sleep, leading to hypoxemia, hypercapnia, and persistent inspiratory efforts against an occluded airway until arousal. Several studies demonstrated that OSAH exerts acute and chronic effects on the cardiovascular system. Thus, although being a respiratory problem, the most important consequences of OSAH are cardiovascular, among which there are arrhythmias. The purpose of this review is to systematically analyse what has been recently published about the relationship between OSAH and every cardiac arrhythmia separately., Methods: We searched Pubmed, Scopus, Web of Science and Cochrane Collaboration databases for 'OSAHS arrhythmias', 'OSAH arrhythmias' and 'OSA arrhythmias'. We analyse 1298 articles and meta-analyses, excluding already edited reviews., Results: Arrhythmias, especially of ventricular origin, are frequent in OSAH. Ventricular premature beats, couplets and ventricular tachycardia runs are even more frequent in patients suffering from heart failure. They may be due to left heart remodelling, overwork and ischaemia and can explain at least some sudden deaths occurring between midnight and 6 a.m. Sinus pauses and atrioventricular blocks are increased according to the severity of the disturbance and may be reduced by continuous positive airway pressure therapy, preventing pace-maker implantation. Finally, atrial fibrillation, resistance against antiarrhythmic drugs and recurrences after surgical procedures are strongly related to OSAH., Conclusion: Arrhythmias are frequent in OSAH. Treatment of OSAH may reduce some of them. An implantable cardioverter-defibrillator and continuous positive airway pressure should be considered in some patients.

Background: In patients with acute heart failure, high levels of N-terminal-pro-brain natriuretic peptide (NT-proBNP) at discharge are associated with worse outcomes. We hypothesized that NT-proBNP-guided therapy may improve prognosis., Methods and Results: Two hundred and seventy-one consecutive patients, admitted for acute heart failure, were prospectively randomized to NT-proBNP-guided therapy or control group. The NT-proBNP-guided therapy group underwent medical treatment intensification when predischarge NT-proBNP was at least 3000 pg/ml. The primary endpoint was cardiovascular death or cardiovascular rehospitalization at day 182. The secondary endpoints were all-cause death, cardiovascular death, cardiovascular rehospitalization, heart failure rehospitalization, and cardiovascular death or heart failure rehospitalization at day 182. Treatment intensification in the NT-proBNP-guided therapy group regarded mainly diuretics. The NT-proBNP strategy was not associated with a significant reduction of the primary endpoint [43% intervention vs. 39% controls, hazard ratio 1.22 (0.84, 1.76), P = 0.305] and of any secondary endpoint. The change of NT-proBNP from predischarge to discharge was associated with the risk of cardiovascular death or cardiovascular rehospitalization through day 182, even after multivariable adjustment., Conclusion: NT-proBNP-guided therapy resulted mainly in an increase of diuretics in acute setting and compared with clinical evaluation alone did not improve prognosis. However, the reduction of NT-proBNP at discharge was an independent predictor of outcomes.

Aims: Cardiovascular diseases affect adult population but risk factors develop as a result of known or assumed behavior since childhood. In Italy, up to 22.2% of children are overweight, 10.6% are obese, and 2.5% have severe obesity., Methods: We performed a systematic review of the literature to identify studies and initiatives addressing health promotion among children in Italy. Given the high heterogeneity of interventions and outcomes assessed we opted to perform a qualitative synthesis of the results. We described also nonrandomized trial where the intervention of primary prevention was very innovative, explained in detail, and reached an improving outcome for participants., Results: We identified 11 projects since 1983, only five were randomized control trials. Three involved children and teachers of primary and secondary schools and were based on specific curricular lectures about health. One was based on a game developed for high schools with the purpose to promote healthy lifestyle and physical activity. The fifth project was based on an enhanced physical activity program., Conclusion: Our results show that school and family should be considered as the privileged places for health promotion. In Italy, the development of scientific-validated lifestyle interventions for children is still an unmet need.

Background: Many studies proved the prognostic importance of aortic stiffness as an independent predictor of cardiovascular morbidity and all-cause mortality. The decrease of arterial compliance has a high prevalence in patients with heart failure and affects both hemodynamics and prognosis. Aortic stiffness is partially caused by excessive activation of the renin-angiotensin-aldosterone system. Spironolactone, a mineralcorticoid receptor antagonist (MRA), has been shown to decrease aortic stiffness and fibrosis in experimental models. However, there are few studies that describe the effects of MRA on aortic stiffness in patients with nonischemic dilated cardiomyopathy., Aims: To evaluate the effect of spironolactone on aortic stiffness in patients with nonischemic dilated cardiomyopathy., Materials and Methods: We randomized (1 : 1) 102 patients with nonischemic dilated cardiomyopathy with New York Heart Association class I-II to receive spironolactone 25 mg/day (up to 100 mg/day) or placebo, in addition to recommended therapy. Aortic stiffness index, aortic strain, aortic distensibility and aortic dimensions were assessed at baseline and after 6 months. All measures were obtained with echocardiography M-mode at 3 cm above the aortic valve on parasternal long axis view and simultaneous brachial arterial pressure with sphygmomanometer., Results: Ascending aorta diameters, aortic stiffness index, aortic distensibility and aortic strain were similar at randomization in the two groups. After 6 months of therapy in the treated group, we found a reduction of aortic stiffness index (7.2 ± 3.5 versus 9.6 ± 4.8 mmHg; P = 0.03) and an increase of aortic distensibility (3.77 ± 1.0 versus 2.92 ± 0.55 mmHg; P = 0.01) and systolic aortic strain (10.0 ± 5.0 versus 8.0% ± 2.1%; P = 0.01). There were no difference in systolic arterial pressure, diastolic arterial pressure and differential pressure in the two groups., Conclusion: Therapy with spironolactone is effective in reducing aortic stiffness in patients with nonischemic dilated cardiomyopathy. This effect could improve hemodynamics supporting the use of MRAs in patients with low New York Heart Association class (I-II).

Introduction: Tako-Tsubo cardiomyopathy (TTC) is an acute cardiomyopathy mimicking acute myocardial infarction. The aim of our study was to define clinical and instrumental features of an Italian population of patients with TTC and to report their short and mid-term outcome., Methods: We retrospectively evaluated 42 patients admitted to our Department with diagnosis of TTC (100% women, age 67 ± 11 years) using Mayo Clinic-modified criteria. In this population, we analyzed the stressful event (if present), the clinical presentation, the ECG and echocardiogram at admission and the markers of myocardial cytonecrosis, such as troponin I, at admission and during the hospitalization. All the patients have been clinically evaluated after 6 months and 1 year of follow-up., Results: In this population, a stressful event before TTC has been detected in 59% of patients. The most common clinical presentation was chest pain (81%) and the major sign was dyspnea (17%). ECG showed negative T waves and ST elevation, respectively, in 45 and 38%. Only 10% had a ST depression and 7% developed a newly acquired complete left bundle branch block. All of these abnormalities disappeared within 1.8 ± 0.9 days. The mean ejection fraction at admission was 35 ± 7% associated with apical (40%), mid-apical (56%) and mid-ventricular (4%) wall motion abnormalities. The recovery of these abnormalities occurred within 10 ± 3 days. At 6-month and 1-year follow-up, no patients had TTC recurrence, and 10 patients at 6 months and 20 patients at 1 year were re-hospitalized for a non-cardiac cause., Conclusion: Our data describe the characteristics of TTC in a small Italian population, which are similarly described in Japanese and North American people. TTC was related to a very low mortality, both in the short and mid term, but the risk of acute heart failure in the acute phase could not be neglected.

Objective: To compare different vascular approaches on clinical outcome of patients undergoing transcatheter aortic valve implantation (TAVI) with self-expandable bioprosthesis., Methods: We included all the patients undergoing CoreValve implantation at our institute between September 2007 and March 2014. They were divided into four groups based on the vascular approach: percutaneous transfemoral (pTF), cut-down transfemoral (cTF), transaxillary (TAx) and transaortic (TAo). Clinical outcomes were evaluated according to Valve Academic Research Consortium-2 recommendations., Results: Out of 322 consecutive patients, 170 (53%) underwent pTF, 76 (23%) cTF, 32 (10%) TAx and 44 (14%) TAo approach. Although the TAx and TAo patients had a higher risk profile, they had a similar outcome compared with the pTF and cTF groups; in particular, there were no differences regarding cardiovascular and all-cause mortality at 30 days, 1 and 2 years, as well as stroke, myocardial infarction, bleeding, major vascular complications, permanent pacemaker implantation and acute kidney injury rates. The observed device success rate was higher in the TAo than in the other approaches (88.6 versus 65.9, 68.7 and 76.3% in the pTF, cTF and TAx groups, respectively; P = 0.019). No differences occurred regarding 30-day early safety and 1-year clinical efficacy across the four groups. Fluoroscopy time, amount of contrast medium used and minor vascular complications were significantly higher in pTF patients, as well as in-hospital stay in the TAo group. Atrial fibrillation and prosthetic valve regurgitation, but not the vascular approach, were independent predictors of all-cause mortality., Conclusion: A more invasive vascular approach, for CoreValve implantation, even in higher risk patients, does not affect early-term, mid-term and long-term outcomes.