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Background to date, more than 243 million COVID-19 cases have been diagnosed globally, with 4.94 million deaths, 489.000 new cases and 8.474 deaths per day. In Italy there are currently 4.73 million cases and 132.000 deaths. It is well known that the entry of the SARS- CoV-2 virus into cells is mediated by the binding between the virus Spike-glycoprotein (S) and the membrane ACE2-receptor (ACE2-R). When SARS-CoV-2 binds to ACE2-R, with subsequent membrane fusion and virus entry into the cell, a down-regulation of these receptors occurs. ACE2 –R downregulation plays a crucial role in the pulmonary and systemic inflammatory response. A serious clinical course appears to be associated with some factors such as age, previous pathologies and comorbidities. However, also a dysregulation of the RAA system linked to a different expression of ACE-2 R and TMPRSS2 gene polymorphisms and different serum levels of soluble ACE2 (sACE2), could be associated with abnormal inflammatory and immune response to SARS-CoV-2 infection. Aim of the Study we aimed to verify whether there is an association between the clinical course of COVID-19 patients (pts) and the presence of more frequent ACE2 and TMPRSS2 single-nucleotide polymorphisms (SNPs) and if sACE2 levels are related to specific ACE2 and TMPRSS2 polymorphic variants. Methods we consecutively enrolled subjects with previous documented SARS-CoV-2 infection and divided our sample into three groups: pts with asymptomatic course; pts with symptomatic course but without the need for hospitalization for COVID-19; pts with severe symptomatic course requiring hospitalization in intensive care unit. Data about age, clinical course, comorbidities, and therapies were collected. Blood samples were taken for the genetic analysis of the most frequent SNPs of the ACE2-R and TMPRSS2 detected in Italian population, in particular genotypic variants TT and CC of ACE2 SNPs 1 and 5 (rate of 5% and 14% respectively) and genotypic variants TT and CC of TMPRSS2 SNPs 2 and 3 (rate of 50% and 30% respective). Results among 178 pts enrolled up to March 2022, we have so far analyzed the genetic polymorphisms of 74 pts.; 21 (28%) were hospitalized for COVID-19, 38 (51%) had symptomatic course without hospitalization and 15 (21%) were completely pauci-asymptomatics. Serum concentrations of sACE2 and distribution of polymorphic variants in the three groups are summarized in Table 1. We found that sACE2 levels were higher in genotypic variant CC of SNP 1 of TMPRSS2 gene (Table 2). Considering that a high concentration of sACE2 outlines a proinflammatory condition, it could be hypothesized that the CC genotype may be a predisposing condition to the cytokine storm of COVID-19. Perspectives: Genetic analysis of ACE2 and TMPRSS2 SNPs will help to clarify the relationship between these polymorphic variant, sACE2 levels, risk of SARS-CoV2 infection and severity of clinical presentation of COVID-19 in patients with or without CV diseases.

Background It is well known that the entry of the SARS- CoV-2 virus into cells is mediated by the binding between the virus Spike-glycoprotein (S) and the membrane ACE2-receptor (ACE2R). When SARS-CoV-2 binds to ACE2R, with subsequent membrane fusion and virus entry into the cell, a down-regulation of these receptors occurs. ACE2R downregulation plays a crucial role in the pulmonary and systemic inflammatory response. Also ACE2 deficiency is thought to play an important role in the pathogenesis of SARS-CoV-2 infection. The down-regulation of ACE2 induced by viral infection could be particularly harmful in subjects with pre-existing ACE2 deficiency, for example due to advanced age, the presence of DM, arterial hypertension or pre-existing heart disease, including HF. Literature data suggest an association between the patient's age and comorbidities and a greater risk of severe clinical course and with a worse prognosis. However, serious clinical pictures requiring hospitalization or leading to death have also been observed in young subjects or subjects without comorbidities. Aim of the Study we aimed to identify predicting factors of a higher risk in terms of severity of the clinical course and worse prognosis in the population of the Brescia area, affected by a large number of cases in the first period of COVID-19 outbreak. In particular, we aimed to verify whether there is correlation between levels of serum ACE2 (sACE2) and the risk of SARS-CoV-2 infection, as well as between sACE2 and the different severity of the clinical manifestations of COVID-19 in patients with and without CV diseases. Methods we consecutively enrolled subjects with previous documented SARS-CoV-2 infection and divided our sample into three groups: pts with asymptomatic course; pts with symptomatic course but without the need for hospitalization for COVID-19; pts with severe symptomatic course requiring hospitalization in intensive care unit. Blood samples were taken for sACE2 dosage. We compared the concentrations of sACE2 in these groups in relation to the age, clinical course, comorbidities, and ongoing therapies. Results at March 2022, we enrolled 178 pts, 51 (28%) were hospitalized for COVID-19, whereas 78 (44%) had symptomatic course without hospitalization and 49 (28%) were completely pauci-asymptomatic. Only 6 pts (4%) had myocarditis or pericarditis SARS-CoV-2-related. Between hospitalized pts, male sex (67%), older age and higher BMI were most frequent. Moreover, chronic heart failure (20%), a diagnosis of cardiopathy (29%) and AF or atrial flutter (22%) were most frequent (Table 1). Plasma concentrations of sACE2 will be dosed and analyzed in relation to the clinical characteristics of each patient. Perspectives ACCEPT study will help to clarify the relationship between ACE2 molecule, the risk of SARS-CoV2 infection and the severity of clinical presentation of COVID-19 in pts with or without CV diseases.

Despite recent advances in chronic heart failure (HF) therapy, the prognosis of HF patients remains poor, with high rates of HF rehospitalizations and death in the early months after discharge. This emphasizes the need for incorporating novel HF drugs, beyond the current approach (that of modulating the neurohumoral response). Recently, new antidiabetic oral medications (sodium-glucose cotransporter 2 inhibitors (SGLT2i)) have been shown to improve prognosis in diabetic patients with previous cardiovascular (CV) events or high CV risk profile. Data from DAPA-HF study showed that dapaglifozin is associated with a significant reduction in mortality and HF hospitalization as compared with placebo regardless of diabetes status. Recently, results from EMPEROR-Reduced HF trial were consistent with DAPA-HF trial findings, showing significant beneficial effect associated with empagliflozin use in a high-risk HF population with markedly reduced ejection fraction. Results from the HF with preserved ejection fraction trials using these same agents are eagerly awaited. This review summarizes the evidence for the use of gliflozins in HF treatment.

AIM To review published literature on the use of quick response (QR) codes within medical and cardiology settings. METHODS Medline, Scopus Search and Cochrane Library were used to conduct the research. Title and abstract review of 376 publications was performed. Papers which discussed the application of QR codes in medical setting were included. A total of 151 articles were reviewed and thematic analysis conducted to understand how QR codes are currently used in the medical setting, the medical areas in which they are mostly used, their applications in cardiovascular area. RESULTS The analysis of 151 articles revealed that QR code technology is mainly used in the medical field to: 1) collect data via survey, 2) educate medical staff or students and 3) provide information about therapies or surgery. The medical area in which QR codes are most used is the clinical one, but only 3.3% of publications concern cardiovascular settings. A third of the QR code-related articles of 2020 is about Covid-19. CONCLUSIONS Different uses of QR codes in medical setting are increasing. QR codes might represent an easy and convenient digital tool to collect data and implement telemedicine programs on a large scale involving also the cardiovascular setting., Graphical Abstract Graphical Abstract

CoronaVIrus Disease-19 (COVID-19) had a huge impact on human health and economy. However, to this date, the effects of the pandemic on the training of young cardiologists are only partially known. To assess the consequences of the pandemic on the education of the cardiologists in training, we performed a 23-item national survey that has been delivered to 1443 Italian cardiologists in training, registered in the database of the Italian Society of Cardiology (SIC). Six hundred and thirty-three cardiologists in training participated in the survey. Ninety-five percent of the respondents affirmed that the training programme has been somewhat stopped or greatly jeopardized by the pandemic. For 61% of the fellows in training (FITs), the pandemic had a negative effect on their education. Moreover, 59% of the respondents believe that they would not be able to fill the gap gained during that period over the rest of their training. A negative impact on the psycho-physical well being has been reported by 86% of the FITs. The COVID-19 pandemic had an unparalleled impact on the education, formation and mental state of the cardiologists in training. Regulatory agencies, universities and politicians should make a great effort in the organization and reorganization of the teaching programs of the cardiologists of tomorrow.

Background Adverse cardiac remodeling is a major risk factor for the development of post myocardial infarction (MI) heart failure (HF). This study investigates the effects of the chymase inhibitor fulacimstat on adverse cardiac remodeling after acute ST-segment-elevation myocardial infarction (STEMI). Methods In this double-blind, randomized, placebo-controlled trial patients with first STEMI were eligible. To preferentially enrich patients at high risk of adverse remodeling, main inclusion criteria were a left-ventricular ejection fraction (LVEF) ≤45% and an infarct size >10% on day 5 to 9 post MI as measured by cardiac MRI. Patients were then randomized to 6 months treatment with either 25 mg fulacimstat (n = 54) or placebo (n = 53) twice daily on top of standard of care starting day 6 to 12 post MI. The changes in LVEF, LV end-diastolic volume index (LVEDVI), and LV end-systolic volume index (LVESVI) from baseline to 6 months were analyzed by a central blinded cardiac MRI core laboratory. Results Fulacimstat was safe and well tolerated and achieved mean total trough concentrations that were approximately tenfold higher than those predicted to be required for minimal therapeutic activity. Comparable changes in LVEF (fulacimstat: 3.5% ± 5.4%, placebo: 4.0% ± 5.0%, P = .69), LVEDVI (fulacimstat: 7.3 ± 13.3 mL/m2, placebo: 5.1 ± 18.9 mL/m2, P = .54), and LVESVI (fulacimstat: 2.3 ± 11.2 mL/m2, placebo: 0.6 ± 14.8 mL/m2, P = .56) were observed in both treatment arms. Conclusion Fulacimstat was safe and well tolerated in patients with left-ventricular dysfunction (LVD) after first STEMI but had no effect on cardiac remodeling.

Aims To compare demographic characteristics, clinical presentation, and outcomes of patients with and without concomitant cardiac disease, hospitalized for COVID-19 in Brescia, Lombardy, Italy. Methods and results The study population includes 99 consecutive patients with COVID-19 pneumonia admitted to our hospital between 4 March and 25 March 2020. Fifty-three patients with a history of cardiac disease were compared with 46 without cardiac disease. Among cardiac patients, 40% had a history of heart failure, 36% had atrial fibrillation, and 30% had coronary artery disease. Mean age was 67 ± 12 years, and 80 (81%) patients were males. No differences were found between cardiac and non-cardiac patients except for higher values of serum creatinine, N-terminal probrain natriuretic peptide, and high sensitivity troponin T in cardiac patients. During hospitalization, 26% patients died, 15% developed thrombo-embolic events, 19% had acute respiratory distress syndrome, and 6% had septic shock. Mortality was higher in patients with cardiac disease compared with the others (36% vs. 15%, log-rank P = 0.019; relative risk 2.35; 95% confidence interval 1.08–5.09). The rate of thrombo-embolic events and septic shock during the hospitalization was also higher in cardiac patients (23% vs. 6% and 11% vs. 0%, respectively). Conclusions Hospitalized patients with concomitant cardiac disease and COVID-19 have an extremely poor prognosis compared with subjects without a history of cardiac disease, with higher mortality, thrombo-embolic events, and septic shock rates.

Early epidemiologic studies in type 2 diabetes suggested that the long-term risk of microvascular and macrovascular complications increase progressively as glucose concentrations rise, inspiring the pursuit of near euglycaemia as a means of preventing these complications in type 1 and type 2 diabetes. Evidence emerging over the past decade, however, showed that the aggressive efforts often needed to achieve low HbA1c levels can ultimately lead to worse clinical outcomes, greater risk of severe hypoglycaemia, and higher burden of treatment. The acknowledgment of the disappointing results obtained with therapies aimed exclusively at improving glycaemic control has led in recent years to a substantial paradigm shift in the treatment of the diabetic patient. The results obtained first with GLP-1RAs and more recently even more with SGLT2i on mortality and CV events have made it clear how other mechanisms, beyond the hypoglycaemic effect, are at the basis of the benefits observed in several cardiovascular outcome trials. And as evidence of the great revolution of thought we are experiencing, there is the recognition of gliflozins as drugs for the treatment not only of diabetic patients but also of non-diabetic patients suffering from HF, as reported in the latest ESC/HFA guidelines. Surely, we still have a lot to understand, but it is certain that this is the beginning of a new era.

Aims Sodium glucose cotransporter type 2 (SGLT2) inhibitors represent a new class of hypoglycemic agents for type 2 diabetes mellitus (T2DM), which act independently of insulin to selectively inhibit renal glucose reabsorption, thereby increasing urinary excretion of glucose. Several studies have demonstrated the cardioprotective effects of SGLT2-i in patients with heart failure (HF), with and without diabetes mellitus. It is also unknown whether these SGLT2is-associated benefits are associated with the amelioration of left or right ventricular function in patients affected by HF with T2DM. Evaluate the effect of SGLT2 inhibitors on left and right ventricular function by conventional and advanced echocardiographic parameters, focusing on speckle tracking echocardiography, in patients with HF and T2DM. Methods and results BEGIN-HF is an international multi-centre registry enrolling outpatients affected by HF and T2DM. Inclusion criteria are HbA1c> 6.5%, eGFR [MDRD] > 45 ml/min/1.73 m2, age > 18 years, FE Conclusions This is the first international multicentre registry evaluating biventricular function by conventional and advanced echocardiography in patients with HF and T2DM starting and no-starting SGLT2i therapy.

Background During the lockdown period in Italy, from March 11th to May 4th 2020, a progressive increase in COVID-19 cases occurred in all Italian regions, in particular in the Lombardy Region. The current rise in COVID-19 cases has led to an increasing involvement of hospitals, in order to face the Coronavirus outbreak, shifting healthcare resources towards the management of COVID+ patients. This has led, on the other hand, to a progressive decrease in hospital admissions due to conditions not associated with SARS-CoV2 infection. During COVID-19 outbreak period, it has been observed a decrease in hospital admissions for acute myocardial infarction. This phenomenon put in serious difficulty the clinical management of COVID-free patients with cardiovascular disease, at the beginning of phase 2 (starting from May 4 2020). Purpose In this scenario, we aimed to verify the impact of telemedicine during lockdown, in comparison with the same period in 2019. Materials and method We analyzed 12-lead ECGs recorded by 5000 country pharmacies, evaluated and stored in one telemedicine platform provided by Health Telematic Network (HTN), in cooperation with our Cardiology Department, Federfarma (Pharmacists' National Association), and Italian National Health Institute. Results During the lockdown period, were recorded 6,104 ECGs in territorial pharmacies, compared to 17,280 ECGs done in the same period in 2019. Chest pain symptom represented the cause of recording ECG in 298 patients (4.88%) during the lockdown period, compared to 402 patients (2.33%) in the same period in 2019, with an increase of 109.86%. In the Lombardy Region, during lockdown period, were reported 118 accesses to territorial pharmacies for chest pain (about 39.50% of total cases in Italy). Among these, 36 accesses were in the province of Brescia (about 30.50%), whereas 28 of them were in the province of Bergamo (about 23.73%). Among ECGs performed, 8 showed typical abnormalities of acute myocardial infarction with ST elevation (STEMI, 2.68%) in the lockdown period, compared to 7 STEMIs (1.74%) detected in the same period in 2019, with an increase of 54.17%. These patients were referred to Emergency Department (ED) suddenly, for the therapeutic intervention. Conclusion These data shown that a large number of patients with cardiovascular symptoms preferred to go to territorial pharmacies rather than hospitals during the COVID outbreak period. Telemedicine played a prominent role in managing patients with cardiovascular symptoms at home. Moreover, this service allowed patients with STEMI to access to the hospitals faster, avoiding the risks of a serious diagnostic delay. Furthermore, by analyzing the data of Lombardy Region, it was possible to show how a significant component of access to local pharmacies for chest pain occurred in the region most affected by the COVID-19 outbreak. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): University of Brescia Number of ECGs recorded for chest painData recorded in Lombardy Region

The chymase inhibitor fulacimstat is developed as a first-in-class treatment option for the inhibition of adverse cardiac remodeling in patients with left ventricular dysfunction (LVD) after acute myocardial infarction (MI). The aim of the study was to examine the safety and tolerability of fulacimstat in patients with LVD after remote MI. A multicenter, multinational randomized, placebo-controlled study was performed in clinically stable patients (40–79 years of age, left ventricular ejection fraction ≤ 45% because of MI in medical history) who were on stable evidence-based standard-of-care therapies for LVD post-MI including an angiotensin converting enzyme inhibitor or angiotensin receptor blocker at doses of at least half the recommended target dose. Patients were treated for 2 weeks with either placebo (n = 12) or 4 different doses of fulacimstat (5 mg twice daily, n = 9; 10 mg twice daily, n = 9; 25 mg twice daily, n = 10; 50 mg once daily, n = 9). Fulacimstat was safe and well tolerated at all examined doses. There were no clinically relevant effects on vital signs or potassium levels compared with placebo treatment. Mean plasma concentrations of fulacimstat increased with the administered dose and reached exposures predicted to be therapeutically active. The safety profile and the absence of effects on blood pressure or heart rate in a chronic patient population having similar comorbidities and receiving similar comedication as patients after acute MI support future clinical trials with fulacimstat in patients after acute MI.

Purpose of Review The nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) pathway plays an important role in the regulation of cardiovascular function, and it is disrupted in heart failure (HF), resulting in decreased protection against myocardial injury. Impaired NO-sGC-cGMP signaling in HF is secondary to reduced NO bioavailability and altered redox state of sGC, which becomes less responsive to NO. The sGC activator cinaciguat increases cGMP levels by direct NO-independent activation of sGC and may be particularly effective in conditions of increased oxidative stress and endothelial dysfunction, and therefore reduced NO levels, at the expense of a greater risk of hypotension. Conversely, sGC stimulators (riociguat and vericiguat) enhance sGC sensitivity to endogenous NO, thus exerting a more physiological action. Recent Findings Clinical trials have suggested the benefit of vericiguat in patients with high-risk HF; in particular, a lower incidence of death from cardiovascular causes or HF hospitalization. Summary Adding vericiguat may be considered in individual patients with HF, and reduced left ventricular ejection fraction (HFrEF) particularly those at higher risk of HF hospitalization.

Background It is known that anticancer treatment can cause adverse cardiovascular (CV) events, influencing patients' survival and quality of life regardless of their cancer prognosis; today there are no defined protocols for the early identification of cardiotoxicity (CTX). Purpose To evaluate the ability of biomarkers, cardiac TnI and NT-proBNP, to predict CTX induced by antineoplastic therapy. Methods We have enrolled women with non-metastatic breast cancer who had to start a treatment with Anthracycline (ANT), in the patients (pts) with HER2+ cancer, Trastuzumab (TRZ) could also be introduced. The presence of a known heart disease, a previous mediastinal irradiation and a previous treatment with ANT, were the main exclusion criteria. All pts underwent complete cardiological evaluation (ECG, Echo) before the beginning of the therapy (T0), after each ANT cycle and every 3 months up to 1 year of follow-up after the end of therapy with ANT. During each visit, a venous sampling was performed for the determination of biomarkers. We collected the data of the routine cardiological visits carried out by the pts in the following 5 years. Results 179pts finished the follow-up,7pts (21%) were hypertensive, 9pts (5%) diabetic, 32pts (18%) dyslipidemics. 53pts (30%) (“TnI+ group”) showed a significant increase in TnI (>0.04ng/mL) or less than this cut-off but persistently >0.015ng/mL in at least 2 measurements; comparing the LVEF of the two groups detected at 1 year follow-up it was observed a significant difference: 60±6.5% in the “TnI+ group” and 63±4.1% in the “TnI− group” (p=0.005); a tendency to significance was observed from the comparison between LVEF measured at baseline compared to that of 1-year follow-up in the “TnI+ group” (62±4.2% vs 60±6.5%, p=0.06); furthermore 7 patients of the “TnI+ group” developed LV systolic dysfunction (according to the definition of the CREC) early in the first year of follow-up (vs 1 pts of the “TnI− group”, p=0.001), with recovery after the introduction of specific cardiology therapy. 76/179 pts (43%) showed NT-proBNP values ≥125 ng/L in at least two consecutive determinations (“NT-proBNP+ group”), in this group 25% of the pts had more than 3 CV risk factors, compared to 11% in the “NT-proBNP− group” (p=0.011), 3/8 pts that showed LV systolic dysfunction were included in the “NT-proBNP+ group”. Conclusion(s) In a homogeneous group of patients with a low CV risk profile, anticancer treatment with low doses of ANT and with TRZ can induce significant changes in plasma TnI levels that can be correlated with early alterations in LV systolic function, but not with major CV events after 5 years. Significant increases in NT-proBNP have also been reported, but there has been no significant correlation with the progressive development of LV dysfunction and HF. The combination of individual clinical risk factors and biomarkers, especially TnI, in a predictive model could allow early identification of CTX. Funding Acknowledgement Type of funding source: None

Background In the last years prognosis of cancer patients (pts) has been improved, but the develop of cardiotoxicity (CTX) in pts with low CV risk treated with cumulative doses of Anthracycline (ANT) considered safe, led to investigate the possible role of the genetic profile in the onset of CTX. Purpose To study the role of some single nucleotide polymorphisms (SNPs) as predictive genetic markers of individual susceptibility to CTX induced by anticancer treatment. Methods We have enrolled women with non-metastatic breast cancer who had to start a therapy with ANT. The presence of a known heart disease, a previous mediastinal irradiation and a previous treatment with ANT, were the main exclusion criteria. All pts underwent complete cardiological evaluation (ECG, echo) before the beginning of the therapy (T0), after each ANT cycle and every 3 months up to 1 year of follow-up after the end of treatment. During each visit, we performed the determination of troponin I (TnI) and NT-proBNP. The genetic profile of each pts was also investigated, analyzing 6 SNPs belonging to 3 different genes (two for each genes) coding for enzymes or enzyme systems involved in the metabolism of ANT. DNA extraction from blood samples was performed using the QIAamp DNA Mini kit (QIAGEN). The DNA extracted was genotyped (by performing TaqMan SNP Genotyping assays) identifying 3 possible variants for each SNPs: homozygosity for the protective and “at risk” variant and heterozygosity. Results 179 pts finished the follow-up and from the analysis of the trend of biomarkers we found that 53 pts (30%) showed a significant increase in TnI (>0.04ng/mL) or less than this cut-off but persistently >0.015ng/mL in at least 2 measurements (“TnI+ group”), in the remaining 126 pts the TnI remained non-measurable (“TnI− group”); 76 pts (43%) showed NT-proBNP values ≥125 ng/L in at least two consecutive determinations (“NT-proBNP + group”),in the remaining 57% of pts this increase was not detected (“NT-proBNP - group”). Comparing “TnI+ group” to “TnI− group” we observed that only the genotyping of the SNPs rs1149222 (G/T) belonging to the ABCB4 gene is distributed differently in the two groups, in particular the homozygosity for the “at risk” variant (G/G) was present in 13% of the pts of the “TnI+ group” vs 5% in the “TnI− group” (p 0.06). The results of the comparison of “NT-proBNP+ group” vs “NT-proBNP− group”, showed that the genotyping of the SNPs rs6759892 (G/T) belonging to the UGT1A6 gene was distributed differently, the homozygosity for the “at risk” variant (G/G) was present in 28% of the “NT-proBNP+ group” vs 17% in the “NT-proBNP− group” (p 0.07). Conclusion Together with the baseline clinical evaluation, genetic markers could contribute to the early identification of pts at high risk of developing CTX especially following treatment with ANT and they could support future therapeutic decisions and the planning of taylored strategies for the prevention of the CTX development. Funding Acknowledgement Type of funding source: None

Several inherited disorders involve chronic fatigue, muscle weakness and pain. These conditions can depend on muscle, nerve, brain, metabolic and mitochondrial defects. A major trigger of muscle weakness and fatigue is exercise. The amount of exercise that triggers symptoms and the frequency of symptoms are highly variable. In this review, the genetic causes and molecular pathways involved in these disorders are discussed along with the diagnostic and treatment options available, with the aim of fostering understanding of the disease and exploring therapeutic options. (www.actabiomedica.it)

Burden symptom in advanced heart failure highly affects quality of life of both patients and caregivers, leading to severe functional limitation and social isolation. Symptoms in the advanced phases of the disease are numerous and often underestimated and undertreated. This negatively affects not only quality of life, but also increases hospitalizations, reduces therapeutic adherence, impairs cardiac function and leads to reduced survival. When symptom control cannot be achieved only with specific cardiologic therapy, optimal care should shift to a combination of life-prolonging and symptom-relief approach, possibly to be initiated as soon as advanced phases are detected. Optimal treatment of severe and invalidating symptoms requires a multi-modal and multi-dimensional approach, as pharmacological therapy represents only a part of a global evaluation that should include spiritual and psycho-social factors, potentially influencing symptom perception. Assessment therefore should rely on multi-modal and multi-dimensional patient-centered score models, such as the Edmonton Symptom Assessment System (ESAS), the Kansas City Cardiomyopathy Questionnaire (KCCQ), or the Integrated Palliative care Outcome Scale (IPOS).Pain, dyspnea, depression, fatigue and less frequent but distressing symptoms, including gastrointestinal disorders (nausea, vomiting, fecal impaction, hiccups), cough, itching, skin xerosis and restless legs syndrome, will be analyzed, and evidence of best palliative practice will be discussed.

Heart failure (HF) is characterized by a pro-thrombotic state, which might aggravate its morbidity and, consequently, mortality. Several and commonly observed comorbidities, such as coronary artery disease, atrial fibrillation (AF), renal dysfunction, and diabetes often complicate HF, increasing the thromboembolic risk. In the past decade, direct oral anticoagulants (DOACs) have been approved for the treatment and prevention of stroke and embolic events in patients with nonvalvular AF. Due to their lower bleeding risk, these drugs are frequently used instead of warfarin; however, some controversies exist on their use in HF patients with or without comorbidities. Indeed, the management of anticoagulation in HF patients with underlying conditions is poorly investigated since these patients are underrepresented or excluded from randomized controlled trials. The aim of this research is to review current evidence on the use of DOACs in HF patients, also discussing their specific use in different clinical scenarios. [Figure not available: see fulltext.]

Early palliative care (PC) integration in advanced and end-stage heart failure has shown to improve quality of life and spiritual well-being and to reduce physical symptoms. Barriers to implementation exist: perception that PC is opposite to "life-prolonging" therapies or is involved only in cancer disease and in end of life, prognostic difficulties in advanced heart failure, comorbidities, discrepancy between patient-reported symptom burden and objective measures of disease severity. This is why it is necessary to focus on patient and caregivers "needs" instead of exclusively numerical-objective measures, in order to emphasize clinical but also psychological, assistential and spiritual elements contributing to quality of life. The most appropriate instruments are "patient-reported outcome measures" (PROMs) or, better, "patient-centered outcome measures" (PCOMs), such as the Needs Assessment Tool: Progressive Disease-Heart Failure (NAT: PD-HF), Integrated Palliative Outcome Scale (IPOS), NECPAL and Supportive and Palliative Care Indicators Tool (SPICT). Finally, it is important to recognize triggers to initiate a PC approach (important changes in disease trajectory, difficult or refractory symptoms, frequent defibrillator shocks or transplant/mechanical support prevision, functional capacity decline, severe comorbidities, communication needs also for advanced care planning).

The right ventricle has become increasingly studied in cardiovascular research. In this article, we describe specific pathophysiological characteristics of the right ventricle, with special focus on functional and molecular modifications as well as therapeutic strategies in right ventricular dysfunction, underlining the differences with the left ventricle. Then we analyze the main imaging modalities to assess right ventricular function in different clinical settings. Finally, we acknowledge main therapeutic advances for treatment of right heart diseases.

Heart failure (HF) is the end result of many different cardiac and non-cardiac abnormalities leading to a complex clinical entity. In this view, the use of biomarkers in HF should be deeply reconsidered; indeed, the same biomarker may carry a different significance in patients with preserved or reduced EF. The aim of this review is to reconsider the role of biomarkers in HF, based on the different clinical characteristics of this syndrome. The role of cardiac and non-cardiac biomarkers will be reviewed with respect of the different clinical manifestations of this syndrome.

Introduction despite good progress in the management of patients with atrial fibrillation (AF), this disease remains one of the major cause of stroke, heart failure, sudden death and cardiovascular morbidity. Screening for silent AF is recommended in high risk population, especially in elderly, but often it is not applied for the absence of medical prescriptions or long waiting times Purpose to evaluate the effectiveness of a remote monitoring through ECG Holter and 12-lead ECG provided by a network of pharmacies across the Country for the screening of AF Methods according to a Ministerial Decree, from 2010 authorized pharmacies may provide specialist outpatient care services. Health Telematic Network, in collaboration with our Cardiology University Department and Federfarma (National Association of Pharmacists), has installed in 4,008 authorized pharmacies across the Country a telematic network connected to a single Telemedicine platform where cardiologists were available for tele-consulting. In order to identify silent or symptomatic AF, 12-lead ECG and ECG Holter monitoring were performed in patients with episodes of palpitation, syncope or pre-syncope or with a history of AF. Informations regarding lenght of AF episodes, mean heart rate and anticoagulant therapy were collected Results From Jan 2017 to Dec 2018 a total of 31,156 ECG Holter monitoring were performed (46% male, mean age 61 years). Among these records, 2390 (8%) showed paroxysmal or persistent AF (53% male, mean age 77±10 years). The lenght of AF episodes was greater of 6 minutes in 14% cases and mean heart rate was greater of 90 bpm in 406 patients (17%). History of AF was not previously known in 669 patients (28%). None of this subgroup of patients and only 18% of patients with known paroxysmal AF were taking anticoagulant therapy. In the same period 196,349 ECG were performed (mean age 78 years) and 17,088 have been carried out in patients aged 65 years or older. Among these group of patients, 831 records showed unknown AF (5%): 356 (43%) high ventricular rate AF, 385 (46%) medium ventricular rate AF and 90 (11%) low ventricular rate AF. All the patients with unknown AF episodes or with frequent high ventricular rate AF episodes were referred to their General Practitioner or Cardiologist for urgent evaluation and therapeutic management. Conclusion our data confirm the important role of a single telematic network in which health care services can be provided timely by authorized pharmacies across all the Country to promote early diagnosis and treatment of AF, then resulting in a likely positive impact on related cardiovascular events

Background Fingolimod is an immunosuppressive drug that prevents the typical autoimmune responses of multiple sclerosis (MS). This drug can cause, even after the first dose, bradycardia and atrioventricular conduction block (AVB). According to a decree of the Committee for Medicinal Products for Human Use (CHMP), the first administration of a dose of fingolimod must meet the following conditions: a) 12-lead electrocardiogram (ECG) and blood pressure (BP) evaluations before first dose administration; b) continuous ECG and BP monitoring every hour during the first 6 hours of treatment. The aim of the study was to evaluate the efficacy of our virtual Intensive Care Unit connected to selected Departments of Neurology for cardiology monitoring via web, during the first dose administration of fingolimod in patients with MS. Methods Health Telematic Network, in collaboration with our Cardiology Department, has installed in several Neurology Departments in the country intensive care equipment with real time monitoring via the web of ECG, BP and oximetry. The telemonitoring system is composed of an IntelliVue MP2 monitor, for 12-lead ECG recording, and by an IntelliVue Philips M3150 Central, for continuous remote monitoring of ECG and the detection and storage of arrhythmias. The HTN Cardiologist thus can evaluate in real time ECG monitored and each alarm detected. Results From Jan 2014 to Dec 2018, 172 sites participated and 6041 patients were enrolled. The telemonitoring system recognized 5116 episodes of bradycardia, 297 first degree AVB, 213 second degree AVB Mobitz I, 48 second degree AVB Mobitz II, 618 pathological lengthening of the QTc interval, single monomorphic ventricular ectopic beats in 266 patients, bigeminy ventricular extrasystoles in 15 patients and polymorphic ventricular extrasystoles in 3 cases. 6 cases of nonsustained ventricular tachycardia occurred and were recognized. Conclusion This web-based real time telemonitoring project was an optimal solution for the administration of the first dose of fingolimod, according to current indications of the CHMP. The RITMO project could lead the way for the use of a multidisciplinary approach for the management of new therapies.

Palliative care is recognized as an approach that improves quality of life of patients and families facing life-threatening illnesses. This is achieved through prevention, early identification, assessment and treatment of symptoms and other psycho-social, spiritual and economic issues. Palliative care is not dependent on prognosis and can be delivered as "simultaneous care", together with disease-modifying treatments and adequate symptom relief. Palliative care relies on coordination across settings of care and offers open communication to patients and caregivers. Recently, there is increasing interest in the potential role of palliative care in refractory, advanced heart failure treated with optimal, maximized therapy.Heart failure is a chronic progressive syndrome characterized by periods of stability interrupted by acute exacerbations, usually leading to reduced functional status. It accounts for approximately one-third of deaths in industrialized countries and is a common cause of hospitalization. Fifty percent of patients with advanced heart failure die within 1 year of diagnosis and 50% of the remainder within 5 years. The trajectory of heart failure is often unpredictable and approximately 30% to 50% of patients die suddenly. Patients with heart failure suffer from numerous symptoms, often resistant to conventional treatments, frequently under-recognized and under-treated. Symptom assessment and control improve quality of life in patients with advanced heart failure; this can be managed at best by collaboration between specialistic teams.Although heart failure is a life-shortening condition, therapeutic and technological advances (such as left ventricular assist devices, coronary revascularization, percutaneous valve implantation, and implantable cardioverter defibrillators) can help healthcare professionals in the management of patients with advanced heart failure, improving global condition and reducing the risk of sudden death. On the other hand, it has to be acknowledged that management of cardiovascular implanted electronic devices towards end of life requires awareness of legal, ethical, religious principles regarding potential withdrawal of life-sustaining therapies.Adequate communication with patients regarding adverse events, end of life, benefits vs burdens of therapies and interventions, treatment preferences, and decision-making should be an issue in early stages of disease. The process of advanced care planning should be clearly documented and regularly reviewed.Barriers to the provision of palliative care in heart failure include clinical issues (disease trajectory), prognostic uncertainty, failure in identification of patients who need palliative care and timing of referral to specialist services, but also misconceptions of patients, families and sanitary staff regarding the role of palliative care, organization problems, and finally educational and time issues.This document focuses on the need of further, coordinated research and work-out on: (i) identification of heart failure patients eligible for palliative care, in terms of clinical and social-psychological issues, (ii) identification of trigger events and timing of referral; (iii) identification of adequate performance indicators/scales for measurement, assessment and follow-up of symptoms and quality of life in end-stage heart failure, including patient-reported outcome measures; (iv) treatment, care and organization strategies and models for advanced/end-stage heart failure ("care management"); and (v) implementation of knowledge and education of healthcare professionals in the fields of communication, ethics, and advanced care planning in heart failure.

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 Heart failure with preserved ejection fraction (HFpEF) represents a major global and economic burden, but its epidemiological, clinical, and outcome data have varied according to study design. Methods and results We conducted a systematic review of published HFpEF clinical trials and observational studies (community-based studies and registries) from August 1998 to July 2013 using PubMed and EMBASE databases. Two independent investigators manually screened and extracted relevant data. We included 62 articles (19 describing clinical trials, 12 describing community-based observational studies, and 31 describing registries). The ejection fraction (EF) cut-off values ranged widely for HFpEF from >40% to >55%. However, differences in EF cut-offs were not clearly associated with incidence and prevalence data across studies. Of all patients with heart failure in community studies, 33–84% had HFpEF, which tended to be higher than reported in registries. The HFpEF patients in included studies were primarily older, white (>70%) patients with hypertension (∼50–90%) and coronary artery disease (up to 60%). All-cause mortality and all-cause hospitalizations ranged from 13% to 23% (26–50 months follow-up) and 55% to 67% (37–50 months follow-up), respectively, in clinical trials; cardiovascular causes accounted for 70% of both outcomes. All-cause mortality tended to be higher in registries than in clinical trials and community-based observational studies up to 5 years into follow-up. Conclusions Important differences in EF thresholds, epidemiological indices, clinical profiles, treatment patterns, and outcomes exist across contemporary HFpEF clinical trials, observational studies, and registries. Precision in definition and inclusion of more uniform populations may facilitate improved profiling of HFpEF patients.

Congestion is the most common reason for admissions and readmissions for heart failure (HF). The vast majority of hospitalized HF patients appear to respond readily to loop diuretics, but available data suggest that a significant proportion are being discharged with persistent evidence of congestion. Although novel therapies targeting congestion should continue to be developed, currently available agents may be utilized more optimally to facilitate complete decongestion. The combination of loop diuretics, natriuretic doses of mineralocorticoid receptor antagonists and vasopressin antagonists represents a regimen of currently available therapies that affects early and persistent decongestion, while limiting the associated risks of electrolyte disturbances, hemodynamic fluctuations, renal dysfunction and mortality.

Objective: Chronic heart failure (CHF) is characterized by several micronutrient deficits. Amino acid supplementation may have a positive effect on nutritional and metabolic status in patients with CHF. Levo-carnosine (b-alanyl-L-histidine) is expressed at a high concentration in myocardium and muscle. Preliminary studies with L-carnosine in healthy individuals have suggested a potential role in improving exercise performance. To our knowledge, no study has been conducted in patients with heart failure. The aim of this study was to test the oral supplementation of L-carnosine and its effects on quality of life and exercise performance in patients with stable CHF. Methods: Fifty patients with stable CHF and severe left-ventricular systolic dysfunction on optimal medical therapy were randomized 1:1 to receive oral orodispersible L-carnosine (500 mg OD) or standard treatment. Left-ventricular ejection fraction (LVEF) was measured by echocardiography. Cardiopulmonary stress test, 6-minute walking test (6MWT) and quality-of-life (visual analog scale score and the EuroQOL five dimensions questionnaire [EQ-5D]) were performed at baseline and after 6 mo. Results: Patients receiving orodispersible L-carnosine had an improvement in 6MWT distance (P ¼ 0.014) and in quality-of-life (VAS score) (P ¼ 0.039) between baseline and follow-up. Compared with controls, diet supplementation with orodispersible L-carnosine was associated with an improvement in peakVO2 (P < 0.0001), VO2 at anaerobic threshold, peak exercise workload, 6MWT and quality-of-life assessed by the EQ-5D test and the VAS score. Conclusion: This study suggests that L-carnosine, added to conventional therapy, has beneficial effects on exercise performance and quality of life in stable CHF. More data are necessary to evaluate its effects on left-ventricular ejection fraction and prognosis in CHF.

Heart failure is a global pandemic affecting an estimated 26 million people worldwide and resulting in more than 1 million hospitalizations annually in both the United States and Europe. Although the outcomes for ambulatory HF patients with a reduced ejection fraction (EF) have improved with the discovery of multiple evidence-based drug and device therapies, hospitalized heart failure (HHF) patients continue to experience unacceptably high post-discharge mortality and readmission rates that have not changed in the last 2 decades. In addition, the proportion of HHF patients classified as having a preserved EF continues to grow and may overtake HF with a reduced EF in the near future. However, the prognosis for HF with a preserved EF is similar and there are currently no available disease-modifying therapies. HHF registries have significantly improved our understanding of this clinical entity and remain an important source of data shaping both public policy and research efforts. The authors review global HHF registries to describe the patient characteristics, management, outcomes and their predictors, quality improvement initiatives, regional differences, and limitations of the available data. Moreover, based on the lessons learned, they also propose a roadmap for the design and conduct of future HHF registries.

The burden of heart failure with preserved ejection fraction (HFpEF) is considerable and is projected to worsen. To date, there are no approved therapies available for reducing mortality or hospitalizations for these patients. The pathophysiology of HFpEF is complex and includes alterations in cardiac structure and function, systemic and pulmonary vascular abnormalities, end-organ involvement, and comorbidities. There remain major gaps in our understanding of HFpEF pathophysiology. To facilitate a discussion of how to proceed effectively in future with development of therapies for HFpEF, a meeting was facilitated by the Food and Drug Administration and included representatives from academia, industry, and regulatory agencies. This document summarizes the proceedings from this meeting.

The purpose of this study is to evaluate long-term effects of spironolactone, an affordable and widely used aldosterone receptor blocker, in patients with heart failure (HF) and mild or no symptoms.The study is a single-blind, placebo-controlled, blinded endpoint, randomized study. Patients with New York Heart Association (NYHA) classes I to II HF and left ventricular ejection fraction40% were randomized to spironolactone or placebo in addition to optimal therapy. The primary endpoint was the composite of death from any cause or cardiovascular hospitalization.A total of 130 patients were randomized to spironolactone (n = 65) or placebo (n = 65). Patients on spironolactone had a better event-free survival for cardiovascular death or cardiovascular hospitalizations and for cardiovascular hospitalizations alone. At multivariable analysis, only spironolactone therapy, left ventricular ejection fraction and serum creatinine levels had an independent prognostic value for the combined endpoint, whereas only spironolactone therapy and serum creatinine levels had an independent prognostic value for cardiovascular hospitalizations alone.Administration of spironolactone reduced the composite of death and cardiovascular hospitalization in patients with NYHA classes I to II HF. These results suggest that spironolactone could be beneficial when administered on top of optimal therapy among patients with HF and mild or no symptoms.

Background: Prognostic stratification in heart failure (HF) is crucial to guide clinical management and treatment decision-making. Currently available models to predict HF outcome have multiple limitations. We developed a simple risk stratification model, based on routinely available clinical information including comorbidities, the Cardiac and Comorbid Conditions HF (3C-HF) Score, to predict all-cause 1-year mortality in HF patients. Methods: We recruited in a cohort study 6274 consecutive HF patients at 24 Cardiology and Internal Medicine Units in Europe. 2016 subjects formed the derivation cohort and 4258 the validation cohort. We entered information on cardiac and comorbid candidate prognostic predictors in a multivariable model to predict 1-year outcome. Results: Median age was 69 years, 35.8% were female, 20.6% had a normal ejection fraction, and 65% had at least one comorbidity. During 5861 person-years follow-up, 12.1% of the patients met the study end-point of all-cause death (n = 750) or urgent transplantation (n = 9). The variables that contributed to outcome prediction, listed in decreasing discriminating ability, were: New York Heart Association class III-IV, left ventricular ejection fraction < 20%, no beta-blocker, no renin-angiotensin system inhibitor, severe valve heart disease, atrial fibrillation, diabetes with micro or macroangiopathy, renal dysfunction, anemia, hypertension and older age. The C statistic for 1-year all-cause mortality was 0.87 for the derivation and 0.82 for the validation cohort. Conclusions: The 3C-HF score, based on easy-to-obtain cardiac and comorbid conditions and applicable to the 1-year time span, represents a simple and valuable tool to improve the prognostic stratification of HF patients in daily practice.

Aims We evaluated the impact of diabetes mellitus (DM) and diabetic therapy on outcomes in patients with reduced ejection fraction (EF) after hospitalization for heart failure (HF). DM is prevalent in patients hospitalized with HF, yet inconclusive data exist on the post-discharge outcomes of this patient population. Methods and results Post-hoc analysis was performed on the EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan) study, a randomized trial of patients hospitalized with HF (n = 4133) with median follow-up of 9.9 months. DM status was determined from intake questionnaires and cross-verified by medication history. Univariate relationships were examined using χ[2] test, t-test, and Wilcoxon tests. The two primary outcomes of (i) all-cause mortality (ACM) and (ii) cardiovascular mortality or HF hospitalization (CVM + HFH) were assessed for those with and without DM and by diabetic treatment strategy using log rank tests and multivariable Cox regression models. DM was present in 40% of participants. Patients with DM were more likely to have hypertension, coronary artery disease, and chronic kidney disease. Diabetes was associated with ACM and CVM + HFH (both P < 0.001). Following multivariate risk adjustment, DM was associated with ACM, but this estimate was imprecise [hazard ratio (HR) 1.16; 95% confidence interval (CI) 1.00–1.34] and remained associated with CVM or HFH (HR 1.17; 95% CI 1.04–1.31). Diabetic control strategy did not independently affect outcomes. Conclusion Diabetes is common in patients hospitalized for heart failure with a reduced EF. These patients have a higher post-discharge CVM and higher HF hospitalizations compared with patients with no diabetes. Different diabetic treatment regimens did not appear to influence post-discharge outcomes.

Despite the clinical and prognostic improvement obtained with the current medical treatment, heart failure (HF) continues to have high morbidity and mortality and its prevalence is increasing in most regions of the world. Thus, there is a need for novel adjunctive therapies that act independently of current neurohormonally and haemodynamically oriented drugs. Nutritional approaches are particularly attractive because they could work additively with established therapies without negative hemodynamic effects. There is growing evidence that omega-3 polyunsaturated fatty acids (n-3 PUFAs) supplementation positively impacts established pathophysiological mechanisms in HF and thus has a potential role for preventing and treating HF. The results of the GISSI-HF trial have indicated that, in patients with chronic HF on evidence-based therapy, long term treatment with PUFAs reduced mortality and hospitalizations for cardiovascular reasons, irrespective of etiology and left ventricular (LV) ejection fraction (EF). The purpose of this review is to summarize the evidence emerged from studies conducted so far on the effect of n-3 PUFAs in HF.

Eur J Clin Invest 2012; 42 (4): 376–383 Abstract Background Diabetes is associated with increased cardiovascular mortality. The aim of our study was to determine the prognostic factors for mortality in patients with type 2 diabetes (T2DM) and coronary artery disease (CAD) who underwent coronary angiography and percutaneous coronary intervention. Materials and methods Four hundred and forty-five consecutive T2DM patients with significant CAD (≥ 75% stenosis) were included in our analysis. All patients underwent standard clinical examination, laboratory tests and transthoracic echocardiography with measurement of the left ventricular ejection fraction. Severity of CAD at the coronary angiography was evaluated using the Gensini score. Clinical follow-up was completed at 1, 3 and 6 years. Results During a mean follow-up of 73·3 ± 22·1 months, 109 patients died (24·5%). Significant determinants of an increased risk of death at multivariable analysis were age (p

Cardio-Renal Syndrome (CRS) is a renal dysfunction occurring in a large percentage of pts hospitalised for congestive heart failure (CHF). It is characterised by an excessive fluid retention inside the body, resistance to conventional medical therapy, worsening renal function (WRF) and higher mortality. The prevalence of CRS is likely increased because of the improved survival of HF patients. WRF occurs frequently among hospitalised HFF and is associated with a significantly worse outcome. Clinical features at admission can be used to identify patients at high risk for developing WRF. The clinical case presented concerns a 70-year-old diabetic man with post-ischemic cardiomyopathy and chronic kidney failure, admitted to our division for acute heart failure. During hospitalisation he showed a progressive WRF and resistance to diuretic treatment. After Ultrafiltration treatment there was a progressive clinical improvement. Many treatments have been investigated in order to improve renal function, but none has been demonstrated to improve clinical outcome. Currently Ultrafiltration is reserved to patients with volume overload when traditional medical therapies fail and/or patients become resistant to diuretics.

Acute heart failure represents an increasingly common cause of hospitalization, and may require the use of inotropic drugs in patients with low cardiac output and evidence of organ hypoperfusion. However, currently available therapies may have deleterious effects and increase mortality. An ideal inotropic drug should restore effective tissue perfusion by enhancing myocardial contractility without causing adverse effects. Such a drug is not available yet. New agents with different biological targets are under clinical development. In particular, istaroxime seems to dissociate the inotropic effect exerted by digitalis (inhibition of the membrane sodium/potassium adenosine triphosphatase) from the arrhythmic effect and to ameliorate diastolic dysfunction (via sarcoendoplasmic reticulum calcium adenosine triphosphatase activation). Additionally, the myosin activator omecamtiv mecarbil appears to have promising characteristics, while genetic therapy has been explored in animal studies only. Further investigations are needed to confirm and expand the effectiveness and safety of these agents in patients with acute heart failure and low cardiac output.

Summary Aims/objectives: This review examines the ‘tako-tsubo-like’ syndrome or transient left ventricular apical ballooning. The aim of this review is a complete evaluation of epidemiology, clinical and instrumental features, pathophysiological mechanisms, therapy and prognosis of this syndrome. Methods: We have evaluated the data from literature for a comprehensive consideration of multiple aspects of this syndrome. Results/findings: Transient left ventricular apical ballooning typically affects women, and the clinical presentation is comparable to acute coronary syndrome with chest pain or sudden dyspnoea, changes in ECG and elevated cardiac enzymes in the absence of significant coronary stenosis, with complete resolution of wall-motion abnormalities in a period of days or weeks. This syndrome is triggered by marked psychological or physiological stress. Several pathophysiological mechanisms have been proposed, such as cathecolamine-mediated cardiotoxicity, abnormalities in coronary microvascular function and multivessel coronary vasospasm. The highest incidence of transient left ventricular apical ballooning is in the Japanese population, but it has been recently identified also in the USA and Europe. Treatment is empirical and supportive. The prognosis is generally favourable, although some deaths have been reported, usually the result of irreversible cardiogenic shock, refractory ventricular arrhythmias, or other catastrophic cardiovascular event. Conclusions/interpretations: We conclude by emphasising the importance of a more deeper knowledge of this syndrome for general physicians and cardiologists and it should be often considered as a possible diagnosis occurring in emergency department and in patients admitted in the Chest Pain Units with a diagnosis of coronary acute syndrome.

Background: The 6-min walking test (6MWT) is a simple test, which does not require expensive equipment or advanced training. It has been used in heart failure patients to assess exercise tolerance, the effects of therapy and prognosis. Accordingly, post-surgical cardiac rehabilitation may be a potential field of application of this test. Materials and method: One thousand three hundred seventy patients (70% males, mean age 64 10 years), consecutively admitted for intensive cardiac rehabilitation, underwent 6MWT within 15 days after different types of cardiac surgery (67% coronary artery bypass graft (CABG), 25% valve replacement, 4% both, 4% other). The 6MWT was repeated in a subgroup of 348 patients after 15 3 days of an in-hospital cardiac rehabilitation programme. Results: 6MWT (expressed as absolute value in metres and as a percentage of the predicted value) was well tolerated in all patients. The mean distance walked in 1370 patients was 304 89 m (corresponding to 58 15% of the predicted value). Distances walked were significantly shorter in older patients than younger (p < 0.05) and in women compared to men (251 78 m, 53 15%, vs 328 34 m, 60 14%, p < 0.001). Furthermore, the absolute distance walked in 6 min was significantly shorter in diabetics compared to non-diabetics (283 85 m vs 302 87 m, p = 0.001) and in no CABG compared to CABG patients (285 91 m vs 303 84 m, p < 0.001); no relation was found between distance walked and left ventricular ejection fraction (p = 0.5). Gender, age,comorbiditiesandtypeofsurgerywereindependentlyassociatedwith6MWTinthemultivariatemodel.Inthesubgroupofpatientsrepeating the 6MWT after the rehabilitation programme, the distance walked significantly increased (from 281 90 m, 51 76%, to 411 107 m, 77 81%, p < 0.001). The extent of improvement observed was similar according to sex, age, presence/absence of diabetes and type of surgery. Conclusions: Our data suggest that 6MWT is feasible and well tolerated in adult and older patients shortly after uncomplicated cardiac surgery and provides reference values for distance walked after cardiac surgery in this population. # 2007 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Aims Brain natriuretic peptide (BNP), NT-proBNP and troponins are useful for the assessment of patients with heart failure. Few data exist about their serial changes and their prognostic value in patients with acute heart failure (AHF). Methods and results NT-proBNP and troponin-T plasma levels were measured at baseline, after 6, 12, 24, 48 h and at discharge in 116 consecutive patients with AHF and no evidence of acute coronary syndrome. NT-proBNP levels were 4421 pg/mL at baseline, declined after 24 h and reached their nadir at 48 h (2703 pg/mL). Troponin-T was detectable in 48% of patients. During a median follow-up of 184 days, 52 patients died or had a non-fatal cardiovascular hospitalisation. At a multivariable analysis including clinical and echo-Doppler variables, NT-proBNP plasma levels at discharge, detectable troponin-T plasma levels, and NYHA class at discharge were the only independent prognostic factors. Conclusion In patients with AHF, NT-proBNP levels decline 24 h after the initiation of intravenous therapy and troponin-T is detectable in 48% of cases. NT-proBNP levels at discharge, detectable troponin-T levels, NYHA class and serum sodium have independent prognostic value.

This article provides information on trials presented at the World Congress of Cardiology 2006 (WCC-2006). This was a joint meeting of the European Society of Cardiology and the World Heart Federation. Heart failure trials dealing with understudied patient populations (e.g., the elderly), trials of new treatments (i.e., immune modulation therapy) and new intervention strategies (i.e., the Cardiac Insufficiency Bisoprol-III study) or patient monitoring (the Home or Hospital Heart Failure study) were presented at this meeting. Among the studies about coronary artery disease treatment, WCC-2006 saw the presentation of the landmark meta-analyses regarding the incidence of late events in patients receiving drug-eluting stents. The main results of these meta-analyses, and the associated debate, are summarised in this article. Finally, the results of other trials of percutaneous patent foramen ovale closure and atrial fibrillation treatment in elderly patients are summarised.

The association between exposure to air pollution and acute cardiovascular (CV) events is well documented; however, limited data are available evaluating the public health safety of various "doses" of particular matter (PM) below currently accepted safety thresholds. We explored the cross-sectional association between PM with aerodynamic diameter

Clinical trials studying the efficacy of n-3 polyunsaturated fatty acids (PUFA) in reducing adverse events after acute myocardial infarction (AMI) have yielded conflicting results, and data regarding the influence of n-3 PUFA treatment after AMI in routine clinical practice are scarce. We conducted a retrospective observational cohort study including patients from 5 Italian Local Health Units who were discharged from the hospital with a primary diagnosis of AMI from January 1, 2010, to December 31, 2011. Using unique patient identifiers, patients were linked across governmental hospital discharge, medication prescription, and mortality databases and followed for 12-months post-index discharge. Patient characteristics and risk of all-cause mortality and repeat AMI were compared by n-3 PUFA prescription after discharge (for outcome analyses, defined as ≥ 2 prescriptions) at a presumed dose of 1 g/day. Overall, 11,269 patients met inclusion criteria, of which 2,425 patients (21.5%) were prescribed n-3 PUFA during follow-up. Patients treated with n-3 PUFA tended to be younger, men, and carry a diagnosis of diabetes and were more likely to be receiving guideline-recommended post-AMI medical therapy, including β blockers, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, statins, and antiplatelet therapy (all p

Background: Adrenergic activation has a central role in the development of HF. The function of the β1- and the α2C-adrenergic receptors is influenced by gene polymorphisms: the β1Arg389 variant is associated with increased β1-receptor sensitivity and the α2C-receptor Del322–325 variant is associated with decreased α2C receptor function and increased norepinephrine release. We hypothesised that these polymorphisms could influence the prevalence of heart failure. Methods: The role of the β1- and α2C-adrenergic receptor gene polymorphisms as risk factors for heart failure (HF) was assessed in an Italian white Caucasian population using a case-control study design. Genomic DNA was analysed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RLFP). Results: We compared 260 Caucasian patients with HF and 230 normal subjects. The β1Arg389 allele was frequent both in the patients with HF (69%) and in the normal subjects (73%). The α2CDel322–325 variant was rare in both groups (9% and 8%, respectively). Patients homozygotes for either the β1Arg389 or the α2CDel322–325 alleles had no increased risk of HF (odds ratio [OR], 0.8; 95%CI: 0.5—1.2 and OR, 0.8; 95% CI: 0.4—1.8, respectively). Patients homozygotes for both the β1Arg389 and the α2CDel322–325 alleles had no increased risk of HF as well (OR: 0.6; 95% CI: 0.2—2.1). Conclusions: β1-ARs and α2C-ARs polymorphisms are not associated with an increased risk of HF in an Italian white Caucasian population.