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Previous studies have shown that circulating chromogranin A (CgA) increases in patients with chronic systolic heart failure (HF). Aim of the present study is to evaluate the potential role of circulating vasostatin-1 (VS-1), a cardioregulatory fragment of CgA, as prognostic marker in patients with chronic HF.The plasma levels of CgA and VS-1 were determined in 80 patients with chronic systolic HF. Patients were followed-up to evaluate the occurrence of cardiovascular (CV) events.CgA and VS-1 plasma levels were significantly higher in patients with CV events at follow-up. VS-1, but not CgA, was associated to NT-proBNP. No significant association of CgA and VS-1 with left ventricular ejection fraction (LVEF) was observed. CgA, NT-proBNP and age, but not VS-1, were independent predictors of CV events.In patients with chronic systolic HF those who experienced CV events had higher levels of VS-1 and CgA. Given its established effect on cardiac cells, the association of VS-1 levels with NT-proBNP levels but not with LVEF, suggests that this fragment might provide complementary information to NT-proBNP and CgA in HF patients.

Purpose. Amiodarone is a source of excess iodine that may induce thyroid dysfunction. The aim of the present analysis was to evaluate the magnitude and time course of 24-hr urinary iodine excretion and its potential relationship with thyroid disorders in patients on antiarrhythmic prophylaxis with amiodarone. Methods. 24-hr urinary iodine excretion and thyroid function were evaluated in 67 patients on chronic amiodarone therapy. All patients were clinically and biochemically euthyroid before starting treatment and were followed up by 6-month measurements of 24-hr urinary iodine excretion and plasma TSH levels. Results. Since amiodarone initiation, 20 patients developed thyroid dysfunction (14 hypothyroidism, 3 subclinical hypothyroidism, 3 hyperthyroidism). No differences were observed in terms of treatment length or urinary iodine levels between patients remaining euthyroid and those developing thyroid dysfunction: urinary iodine in the euthyroid group was 8094 µg/24h (IQR 4082-10766) vs 10851 µg/24h (IQR 8529-12804) in the thyroid dysfunction group at 6 months (p = 0.176) and 8651 µg/24h (IQR 6924-11574) vs 8551 µg/24h([IQR 4916-13580) (p = 0.886) at one year from amiodarone initiation. The occurrence of thyroid dysfunction was equally distributed among patients taking amiodarone for more than one year versus those under treatment for less than one year. Upon amiodarone withdrawal, normal range of urinary iodine was achieved after a mean time of 15.2 ± 7.7 months. Conclusion. These results suggest no correlation between 24-hr urinary iodine excretion and thyroid dysfunction in patients on amiodarone therapy. Thyroid disorders following amiodarone administration likely depend on the individual predisposition to iodine load.

Background Guidelines recommend betablockers (BB) as first line therapy in symptomatic patients with hypertrophic cardiomyopathy (HCM). A secondary role in the therapeutic algorithm is assigned to non-dihydropyridine calcium channel blockers (ND-CCB). Since no randomized comparison trials between the two drugs have been made so far, the aim of the present analysis was to evaluate the prognostic impact of BB and ND-CCB in a cohort of patients with HCM, either obstructive or not. Methods From a cohort of 1434 patients with a diagnosis of HCM included in the French register REMY, we retrospectively analysed 601 individuals treated with BB or ND-CCB. Patients taking both BB and ND-CCB or none, patients who already had an implantable cardioverter defibrillator or a pacemaker and who had already undergone a procedure of atrial fibrillation (AF) ablation or of septal reduction therapy were excluded. Results Out of 601 HCM patients, 545 (91%) were treated with BB and 56 (9%) with ND-CCB. At 8-year follow-up no differences were observed as regard the composite endpoint of cardiovascular death, hospitalization for heart failure and hospitalization for AF (133 [24%] vs. 9 [16%] for patients taking BB or ND-CCB respectively, HR 1.84, 95% CI 0.94–3.63). Patients taking ND-CCB were less symptomatic at long-term follow-up but experienced more drug interruptions or changes. Conclusions In a real-world cohort of patients with HCM, ND-CCB therapy was not associated with a higher incidence of adverse events compared to BB therapy.

Aims Cardiovascular sequelae may occur in patients recovered from COVID-19. Recent studies have detected a considerable incidence of subclinical myocardial dysfunction – assessed with speckle-tracking echocardiography – and of long-COVID symptoms in these patients. This study aimed to define the long-term prognostic role of subclinical myocardial dysfunction and long-COVID condition in patients recovered from COVID-19 pneumonia. Methods and Results We prospectively followed-up 110 patients hospitalized at our Institution due to COVID-19 pneumonia in April 2020 and then recovered from SARS-CoV-2 infection. A 6-month clinical and echocardiographic evaluation was performed, followed by a 21-month clinical follow-up. The primary outcome was major adverse cardiovascular events (MACE), a composite of myocardial infarction, stroke, heart failure hospitalization and all-cause mortality. A subclinical myocardial dysfunction – defined as an impairment of left ventricular global longitudinal strain (≥ -18%) - was identified at 6-month follow-up in 37 patients (34%), was associated with an increased risk of long-term MACE with a good discriminative power (AUC: 0.73) and resulted a strong independent predictor of extended MACE in a multivariate regression analysis (OR 9.29, 95%CI 2.20–39.3, p=0.002). Long-COVID condition was not associated with a worse long-term prognosis, instead. Conclusion In patients recovered from COVID-19 pneumonia, a subclinical myocardial dysfunction is present in one third of the whole population at 6-month follow-up and is associated with a higher risk of MACE at long-term follow-up. Speckle-tracking echocardiography is a promising tool to optimise the risk-stratification in patients recovered from COVID-19 pneumonia, while the definition of a long-COVID condition has not prognostic relevance.

Recommended therapy for calcific degenerative aortic stenosis (AS) is still aortic valve replacement (AVR), either transcatheter or surgical, since no conclusive efficacy has been determined in slowing the degenerative process by medical therapy.This paper offers a brief overview of molecular mechanisms leading to calcification of aortic valve. It is then focused on potential markers of disease progression, as observed in many observational studies. Finally it provides a comprehensive review of drugs already tested in in vitro and human studies in order to slow aortic valve stenosis process.Despite research providing numerous molecular pathways underlying the calcification process, further efforts must be made to understand risk factors linked to disease progression. Some existing treatments that have already provided survival benefits in many features of cardiovascular diseases are currently being tested with promising results. In the near future new drugs acting on specific pathways by techniques such as monoclonal antibodies and RNA interference, are expected to provide better medical solutions for this ever growing number of patients.

As buildings account for approximately 40% of global energy consumption and associated greenhouse gas emissions, their role in decarbonizing the power grid is crucial. The increased integration of variable energy sources, such as renewables, introduces uncertainties and unprecedented flexibilities, necessitating buildings to adapt their energy demand to enhance grid resiliency. Consequently, buildings must transition from passive energy consumers to active grid assets, providing demand flexibility and energy elasticity while maintaining occupant comfort and health. This fundamental shift demands advanced optimal control methods to manage escalating energy demand and avert power outages. Reinforcement learning (RL) emerges as a promising method to address these challenges. In this paper, we explore ten questions related to the application of RL in buildings, specifically targeting flexible energy management. We consider the growing availability of data, advancements in machine learning algorithms, open-source tools, and the practical deployment aspects associated with software and hardware requirements. Our objective is to deliver a comprehensive introduction to RL, present an overview of existing research and accomplishments, underscore the challenges and opportunities, and propose potential future research directions to expedite the adoption of RL for building energy management.

Aims Whether CTO-PCI (chronic total occlusions—percutaneous coronary intervention) offers clinical benefit over optimal medical therapy is still a matter of debate. Viability and ischaemia assessment could improve selection of candidates to PCI. Traditionally, well-developed collaterals are considered a marker of myocardial viability in CTO territory. Current literature offers few data concerning the relationship between viability/ischaemia and collaterals distribution. Methods and results We retrospectively analysed the Cardiovascular Magnetic Resonance (CMR) studies and coronary angiographies of patients with at least one CTO referred at Humanitas Research Hospital between June 2009 and September 2020. We included 131 patients who underwent CMR with LGE assessment; of them, 111 (85%) underwent stress-CMR with adenosine. AHA segments (16 segment/patient for a total of 2096 segment assessed) were assessed on three short axis projection and scored for WMSI on cine images, for the presence of ischaemia on first pass perfusion, and for viability on LGE images. Viability was defined as LGE transmurality ≤50% and WMSI (wall motion score index) >1. Patients were divided in three groups according to collaterals distribution at coronary angiography: Patients with TD collaterals were more likely to have viable segments in the CTO-territory (90% of the segments in TD, 76% in WD, and 71% in PD, coeff. 0.107, P Conclusions The presence of myocardial viability is slightly associated with the degree of coronary collateralization at coronary angiography while the amount of ischaemia is not. Stress CMR should be considered in CTO patients before a reopening attempt.

Objectives The aim of the present analysis is to evaluate the clinical impact of chronic total occlusions (CTOs) recanalization in patients with left ventricular (LV) systolic dysfunction. Background According to contemporary knowledge, patient selection for percutaneous CTO revascularization is not yet standardized. In particular, data on outcomes in patients with LV systolic dysfunction undergoing percutaneous coronary intervention (PCI) for CTO are scarce. Methods From a total of 2,421 consecutive patients with at least one CTO, 436 patients with ejection fraction (EF) ≤45%, who were referred for coronary angiography between January 1998 and September 2014, were selected. Patients with successful recanalization of the target CTO were assigned to CTO-revascularized group and those with failed or not attempted recanalization to the CTO-not revascularized (CTO-NR) group. Study endpoints were all-cause death, cardiac death, and occurrence of myocardial infarction on follow-up. Results Out of 436 CTO patients with reduced EF, 228 (52.3%) were successfully recanalized and 208 patients (47.7%) were not, either due to CTO-PCI failure (n = 106, 24.3%) or because CTO-PCI was not attempted (n = 102, 23.4%). At long-term follow-up, CTO-NR patients had significantly higher rate of overall (p = .021) and cardiac mortality (p = .035) compared to those successfully revascularized. Conclusion In patients with systolic LV dysfunction (EF ≤ 45%), CTO revascularization was associated with significant lower rate of total and cardiac mortality compared to those with nonrevascularized CTO.

Energy system models based on the TIMES framework can explore possible energy futures through the construction of a network of technological processes, to satisfy a set of exogenously imposed service demands at the least-cost system configuration. This work presents a methodology aimed at supporting decision-makers in finding optimal energy-system configuration in a complex energy environment, characterized by uncertain information. First, the EUROfusion TIMES Model is used to assess the sensitivity of different long-term evolutions of the European energy system, with particular reference to the road transport sector, considering different trends for the prescribed future variations of investment cost and vehicle efficiency. In a second step, the Stochastic Multicriteria Acceptability Analysis is used to critically evaluate the alternative optimal configurations proposed by the model simulations under a set of economic and environmental criteria. The results of the analysis allow the discussion of the influence of such criteria on the different alternative cases, complementing the cost minimization approach. In the case study considered here, high penetrations of electric vehicles in the road fleet are favored by economic, environmental and energy-related priorities.

Background Myocardial injury is frequent among patients hospitalized with coronavirus disease-2019 (COVID-19) and is associated with a poor prognosis. However, the mechanisms of myocardial...

Demand side management at district scale plays a crucial role in the energy transition process, being an ideal candidate to balance the needs of both users and grid, by managing the volatility of renewable sources and increasing energy flexibility. The presented study aims to explore the benefits of a coordinated approach for the energy management of a cluster of buildings to optimise the electrical demand profiles and provide services to the grid without penalising indoor comfort conditions. The proposed methodology makes use of a fully data-driven control scheme which exploits Long Short-Term Memory (LSTM) Neural Networks, and Deep Reinforcement Learning (DRL). A simulation environment is introduced to train a DRL controller to manage the operation of heat pumps and chilled and domestic hot water storage for a cluster of four buildings. LSTM models are trained with synthetic data set created in EnergyPlus and are integrated into simulation environment to evaluate the indoor temperature dynamics in each building. The developed DRL controller is tested against a manually optimised Rule Based Controller (RBC). Results show that the DRL algorithm is able to reduce the overall cluster electricity costs, while decreasing the peak energy demand by 23% and the Peak to Average Ratio (PAR) by 20%, without penalizing indoor temperature control.

Buildings are responsible for about 26% of the total final energy consumption in Italy. Therefore, building retrofitting represents an opportunity to achieve economic and environmental benefits. However, a challenging task is the application of robust methodologies for evaluating cost-optimal retrofit measures. The paper evaluates, in terms of multiple criteria-based approach, several retrofitting alternatives selected for a typical office building in Italy. The alternatives are evaluated considering economic, environmental, and technical requirements and are compared by means of a Stochastic Multicriteria Acceptability Analysis (SMAA) method, able to consider uncertainties in the criteria evaluation. Three different stakeholder preferences are analyzed and compared with the aim to point out the importance of preference information in multicriteria analysis. The results highlight that, when the preference is the investment cost, for the case study analyzed the most suitable solution is represented by a gas boiler and electricity withdrawn from the market. On the other hand, when the operational cost has the same or more importance than the investment cost, the best solution is represented by a micro-CHP coupled with PV plant. Lastly, the analysis highlights that the main driver of a building retrofit is of economic nature and that, depending on the actors involved, a precise study of preference information could influence the outcome of the analysis.

Advanced control strategies can enable energy flexibility in buildings by enhancing on-site renewable energy exploitation and storage operation, significantly reducing both energy costs and emissions. However, when the energy management is faced shifting from a single building to a cluster of buildings, uncoordinated strategies may have negative effects on the grid reliability, causing undesirable new peaks. To overcome these limitations, the paper explores the opportunity to enhance energy flexibility of a cluster of buildings, taking advantage from the mutual collaboration between single buildings by pursuing a coordinated approach in energy management. This is achieved using Deep Reinforcement Learning (DRL), an adaptive model-free control algorithm, employed to manage the thermal storages of a cluster of four buildings equipped with different energy systems. The controller was designed to flatten the cluster load profile while optimizing energy consumption of each building. The coordinated energy management controller is tested and compared against a manually optimised rule-based one. Results shows a reduction of operational costs of about 4%, together with a decrease of peak demand up to 12%. Furthermore, the control strategy allows to reduce the average daily peak and average peak-to-average ratio by 10 and 6% respectively, highlighting the benefits of a coordinated approach.

The imperative to reduce emissions to counteract climate change has led to the use of renewables progressively in more areas. Looking at district heating, there is a growing interest in coupling current production systems and carbon-neutral technologies. This paper presents a methodology to support decision making about carbon-neutral technologies for district heating. The process is organized in two stages, the first one aims at optimizing the different carbon-neutral technologies according to an objective function and assess uncertainties and dependencies. In the second stage, the alternatives are evaluated using Stochastic Multicriteria Acceptability Analysis (SMAA), a simulation-based method specifically designed to consider imprecise information. The methodology was applied to a case-study in Torino, Italy, which simulates the city district heating network at a smaller scale, with the aim to explore strategies for replacing gas boiler with more sustainable technologies. According to preference information provided by decision makers, the most preferred alternative resulted in the introduction of a solar heat plant combined with an increase size of daily heat storage. Solar heat can benefit from incentives while reducing operational costs and emissions, maximizing the use of carbon-neutral heat thanks to the storage.

Ivabradine is a selective and specific inhibitor of If current. With its pure negative chronotropic action, it is recommended by European Society of Cardiology and American College of Cardiology/American Heart Association guidelines in symptomatic heart failure patients (NYHA ≥ 2) with ejection fraction 35% or less, sinus rhythm and heart rate (HR) at least 70 bpm, despite maximally titrated β-blocker therapy. Data supporting this indication mainly derive from the SHIFT study, in which ivabradine reduced the combined endpoint of mortality and hospitalization, despite the fact that only 26% of patients enrolled were on optimal β-blocker doses. The aim of the present analysis is to establish the real-life eligibility for ivabradine in a population of patients with systolic heart failure, regularly attending a single heart failure clinic and treated according to guideline-directed medical therapy (GDMT). The clinical cards of 308 patients with heart failure with reduced ejection fraction (HFrEF) through a 68-month period of observation were retrospectively analyzed. GDMT, including β-blocker up-titration to maximal tolerated dose, was implemented during consecutive visits at variable intervals. Demographic, clinical and echocardiographic data were collected at each visit, together with 12-leads ECG and N-terminal pro-B-type natriuretic peptide levels. Out of 308 analyzed HFrEF patients, 220 (71%) were on effective β-blocker therapy, up-titrated to effective/maximal tolerated dose (55 ± 28% of maximal dose) (HR 67 ± 10 bpm). Among the remaining 88 patients, 10 (3.2%) were on maximally tolerated β blocker and ivabradine; 21 patients (6.8%), despite being on maximal tolerated β-blocker dose, had still HR ≥70 bpm, ejection fraction 35% or less and were symptomatic NYHA ≥2, being therefore eligible for ivabradine treatment. The remaining 57 (18%) patients were not on β blocker due to either intolerance or major contraindications. Among them, 13 (4%) were taking ivabradine alone. Of the final 44 (14%) patients, 27 (9%) showed an inadequate HR control (74 ± 6 bpm). Of these, only eight (3%) patients resulted to be eligible for ivabradine introduction according to HR and ejection fraction parameters. Overall ivabradine was indicated in 52 patients (16.8%) out of 308 enrolled.In conclusion, in a carefully managed population of patients with moderate and stable HFrEF, in which optimal GDMT is properly attained, indication to ivabradine treatment is around 17%.

It is under development a biomass gasification plant based on a 1 MW th bubbling fluidized bed (BFB) reactor with internal recirculation. Compared to conventional BFB design, the mechanism of internal circulation of solids can give beneficial effect to the process in terms of biomass conversion efficiency into gaseous product and gas quality. A model describing the process of biomass gasification in the two reaction chambers was developed. Expected results were preliminarily validated by experimental results obtained at a bench scale facility working on the same gasification concept. © 2013 The Authors.