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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.

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: Heart failure (HF) affects approximately 26 million people worldwide. With an aging global population, innovative approaches to HF evaluation and management are needed to cope with the worsening HF epidemic. The aim of the Real-Life Multimarker Monitoring in Patients with Heart Failure (REALIsM-HF) study (NCT03507439) is to evaluate a composite instrument comprising remote, real-time, activity-monitoring devices combined with daily electronic patient-reported outcome (ePRO) items in patients who have been hospitalized for HF and are undergoing standard HF assessment (e.g., 6-min walking distance [6MWD], blood biomarkers, Kansas City Cardiomyopathy Questionnaire [KCCQ], and echocardiography). Methods: REALIsM-HF is an ongoing, 12-week, observational study enrolling 80–100 patients aged ≥45 years with HF with preserved ejection fraction (HFpEF; EF ≥45%) or reduced EF (HFrEF; EF ≤35%). Statistical analyses will include examining the association between data from wearables (the AVIVO© mobile patient management patch or VitalPatch© biosensor, and the DynaPort MoveMonitor©), daily ePROs, and conventional HF metrics (e.g., serum/plasma biomarkers, 6MWD, KCCQ, and echocardiographic parameters). The feasibility of and patient compliance with at-home devices will be documented, and the data captured for the purpose of establishing reference values in patients with HFpEF or HFrEF will be summarized. Conclusions: The REALIsM-HF study is to evaluate the longitudinal daily activity profiles of patients with HF and correlate these with changes in serum/plasma biomarker profiles, symptoms, quality of life, and cardiac function and morphology to inform the use of wearable activity monitors for developing novel therapies and managing patients.

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.

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

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.

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.

Despite recent advances in chronic heart failure management (either pharmacological or non-pharmacological), the prognosis of heart failure (HF) patients remains poor. This poor prognosis emphasizes the need for developing novel pathways for testing new HF drugs, beyond neurohumoral and hemodynamic modulation approaches. The development of new drugs for HF therapy must thus necessarily focus on novel approaches such as the direct effect on cardiomyocytes, coronary microcirculation, and myocardial interstitium. This review summarizes principal evidence on new possible pharmacological targets for the treatment of HF patients, mainly focusing on microcirculation, cardiomyocyte, and anti-inflammatory therapy.

The Covid-19 pandemic affected large part of Italy since February 2020; we, therefore, aimed to assess the impact of 2020 SARS-CoV-2 outbreak on telemedicine management of cardiovascular disease (CVD) in Italy. We analyzed data from three telemedicine dispatch centers, one located in Genoa, serving private clients (pharmacies, general practitioners), one in Brescia, serving pharmacies, and one in Bari, serving regional public STEMI network and emergency medical service in Apulia (4 million inhabitants). Demographic data and principal electrocardiogram diagnosis were collected and analyzed. Records from the time interval March 1, 2020 and April 1, 2020 were compared with the corresponding period in 2019. The comparative analysis of data shows a 54% reduction of telemedicine electrocardiogram transmission in Genoa telemedicine center (from 364 to 166), 68% in Brescia (from 5.745 to 1.905), 24% in Bari (from 15.825 to 11.716); relative reduction according to electrocardiogram diagnosis was 38% for acute coronary syndrome, 40% for other acute CVD in Genoa center, 24% for acute coronary syndrome, and 38% for other acute CVD in Bari. Male/female ratio remained substantially unchanged. A dramatic reduction of telemedicine access for CVD was observed during Covid-19 outbreak in March 2020 in Italy. The reduction was substantially consistent for all electrocardiogram findings, ACS, other acute CVD and normal.

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.]

Background Elamipretide, a novel mitochondrial modulating agent, improves myocardial energetics; however, it is unknown whether this mechanistic benefit translates into improved cardiac structure and function in heart failure (HF) with reduced ejection fraction (HFrEF). The objective of this study was to evaluate the effects of multiple subcutaneous doses of elamipretide on left ventricular end systolic volume (LVESV) as assessed by cardiac magnetic resonance imaging. Methods We randomized 71 patients with HFrEF (LVEF ≤ 40%) in a double-blind, placebo-controlled trial in a 1:1:1 ratio to receive placebo, 4 mg or 40 mg elamipretide once daily for 28 consecutive days. Results The mean age (standard deviation) of the study population was 65 ± 10 years, 24% were females, and the mean EF was 31% ± 7%. The change in LVESV from baseline to week 4 was not significantly different between elamipretide 4 mg (89.4 mL to 85 mL; difference, −4.4 mL) or 40 mg (77.9 mL to 76.6 mL; difference, −1.2 mL) compared with placebo (77.7 mL to 74.6 mL; difference, −3.8 mL) (4 mg vs placebo: difference of means, −0.3; 95% CI, −4.6 to 4.0; P = 0.90; and 40 mg vs placebo: difference of means, 2.3; 95% CI, −1.9 to 6.5; P = 0.28). Also, no significant differences in change in LVESV and LVEF were observed between placebo and either of the elamipretide groups. Rates of any study drug-related adverse events were similar in the 3 groups. Conclusions Elamipretide was well tolerated but did not improve LVESV at 4 weeks in patients with stable HFrEF compared with placebo.

The increasing number of patients with heart failure HF and comorbidities is due to aging population and increase of life expectancy of patients with cardiovascular disease. Encouraging results derived by recent trials may suggest some comorbidities as new targets for new drugs, highlighting the need for a better understanding of the comorbidities’ effects in HF patients and the need of a multidisciplinary approach for the management of chronic HF with comorbidities. We report a brief review about main cardiovascular and non-cardiovascular comorbidities in HF patients in order to update physicians and researchers engaged in the HF research or in “fight against heart failure.”

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

We studied safety and tolerability of neladenoson bialanate, a novel oral selective partial adenosine A1 receptor agonist that maintains the cardioprotective effects of adenosine without the undesired side effects of a full agonist, in 2 pilot studies in patients with heart failure with reduced ejection fraction (HFrEF). The β-blocker interaction study was a single-blind, placebo-controlled study on the effects of a 30-mg single dose of neladenoson bialanate on atrioventricular (AV) conduction in 11 patients with HFrEF treated with β-blockers. The PARSiFAL pilot study was a double-blind, placebo-controlled study on the effects of a 7-day treatment with 10 or 20 mg neladenoson bialanate or placebo in 31 patients with HFrEF on β-blocker therapy. In the β-blocker interaction study with 11 HFrEF patients, no second- or third-degree AV block was detected on 48-hour Holter monitoring. In the 31 HFrEF patients included in the PARSiFAL pilot study, no second- or third-degree AV blocks were observed during 24-hour Holter monitoring, and no effects were seen on heart rate and blood pressure. Median absolute changes in LVEF, measured by cardiac magnetic resonance, were 1.9% (interquartile range -1.1 to 4.3), 0.3% (-1.4 to 2.7), and 2.2% (0.4 to 4.5), in the placebo, 10-mg, and 20-mg groups, respectively. Treatment of HFrEF patients with the novel partial adenosine A1 agonist neladenoson bialanate appeared to be safe in 2 small pilot studies, and no atrioventricular conduction disorders or neurological side effects were observed. No significant early changes in cardiac function were detected.

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.

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.

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.

Cardiovascular disease (CVD) accounts for more than 17 million deaths per year worldwide. It has been estimated that the influence of lifestyle on CVD mortality amounts to 13.7% for smoking, 13.2% for poor diet, and 12% for inactive lifestyle. These results deeply impact both the healthy status of individuals and their skills in working. The impact of CVD on productivity loss accounts for the 24% in total costs for CVD management. Mediterranean diet (MedD) can positively impact on natural history of CVD. It is characterized by a relatively high consumption of inexpensive and genuine food such as cereals, vegetables, legumes, nuts, fish, fresh fruits, and olive oil as the principal source of fat, low meat consumption and low-to-moderate consumption of milk, dairy products, and wine. Its effects on cardiovascular health are related to the significant improvements in arterial stiffness. Peripheral artery disease, coronary artery disease, and chronic heart failure are all positively influenced by the MedD. Furthermore, MedD lowers the risk of sudden cardiac death due to arrhythmias. The present narrative review aims to analyze the effects of MedD on CVD.

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.

Elevated plasma levels of homocysteine is associated with increased risk of thrombotic and atherosclerotic vascular disease. Several studies have demonstrated that hyperhomocysteinemia is an indipendent risk factor for vascular disease and is associated to heart failure. However there are no data regarding the association between homocysteine and various objective as well as subjective measures of heart failure. We hypothesized that plasma homocysteine is associated with clinical and echocardiographic signs of heart failure. On this ground we have analysed levels of homocysteine in patients with heart failure and possible correlation between these levels and clinical-functional pattern (NYHA class and ejection fraction). Methods: Plasma homocysteine levels were determined in 123 patients with dilated cardiomyopathy (59 males, 64 females, mean age 67±10 years, mean EF 31±11% and mean NYHA 2.4±0.9, 47 idiopatic and 76 postischemic cardiomyopathy) and 85 healthy control subjects (homogeneus group for sex and age). Patients with chronic renal failure, vitamin B12 and folate deficiency or factors affecting homocysteine plasma levels were escluded from this study. Homocysteine levels were determined in coded plasma samples by immunoenzimatic methods. Results: Patients with heart failure had a higher homocysteine level (mcg/L) than control subjects (21.72±10.28 vs 12.9±6.86, p

Because of the recent advances in chemotherapeutic protocols, cancer survival has improved significantly, although cardiovascular disease has become a major cause of morbidity and mortality among cancer survivors: in addition to the well-known cardiotoxicity (CTX) from anthracyclines, biologic drugs that target molecules that are active in cancer biology also interfere with cardiovascular homeostasis.Pharmacological and non-pharmacological strategies to protect the cardiovascular structure and function are the best approaches to reducing the prevalence of cardiomyopathy linked to anticancer drugs. Extensive efforts have been devoted to identifying and testing strategies to achieve this end, but little consensus has been reached on a common and shared operability.Timing, dose and mode of chemotherapy administration play a crucial role in the development of acute or late myocardial dysfunction. Primary prevention initiatives cover a wide area that ranges from conventional heart failure drugs, such as β-blockers and renin-angiotensin-aldosterone system antagonists to nutritional supplementation and physical training. Additional studies on the pathophysiology and cellular mechanisms of anticancer-drug-related CTX will enable the introduction of novel therapies.We present various typologies of prevention strategies, describing the approaches that have already been used and those that could be effective on the basis of a better understanding of pharmacokinetic and pharmacodynamic CTX mechanisms.

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.

International audience; Both hyperkalemia and hypokalemia may be related to heart failure (HF) therapy and are associated with adverse outcomes. Abnormalities in serum potassium levels in hospitalized patients with HF and reduced ejection fraction (EF) have not been previously investigated. A post hoc analysis was performed in 1,907 hospitalized patients with worsening HF and reduced EF in the placebo arm of the Efficacy of Vasopressin Antagonism in HF Outcome Study with Tolvaptan (EVEREST) trial. Serum potassium was measured at randomization and at discharge or day 7. The co-primary end points were all-cause mortality (ACM) and cardiovascular mortality or the first HF hospitalization (CVM + HFH). The association between inhospital change in potassium levels and time to outcomes was evaluated using multivariate Cox regression models. Study participants had a mean age of 65.6 ± 12.0 years and were on optimal guideline-directed medical therapies, including β blockers (77%), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (85%), and aldosterone antagonists (55%). Baseline potassium concentration was 4.3 ± 0.6 mEq/l, and hyperkalemia or hypokalemia was seen in 6.5% of the participants. On average, serum potassium level increased by 0.21 ± 0.66 mEq/l, 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.

Background We hypothesised that the polymorphisms of the genes encoding for b1and the b2-adrenoceptors may have a role in the pathogenesis of heart failure (HF). We therefore compared the polymorphisms of the b1-adrenoceptor gene (Arg389Gly), the b2-adrenoceptor gene (Arg16Gly, Gln27Glu) and their combinations in patients with HF and normal subjects living in the same area. Methods and results A total of 256 cases with HF (left ventricular ejection fraction 640%) and 230 normal subjects were enrolled. The b1- and b2-adrenoceptor gene polymorphisms were assessed by PCR, followed by restriction enzyme digestion. No differences were observed in the distribution of any of the three genotypes studied in patients with HF and normal subjects. An analysis of the genotype combinations showed a non-significant increase in the risk of HF associated with the Arg389Gly16Gln27 (odds ratio=1.4; 95%CI 0.5‐3.6) and Arg389Gly16 Glu27 (odds ratio=1.2; 95%CI, 0.5‐2.8) homozygous allele combinations. Conclusion None of the three most common polymorphisms of b-adrenoreceptors are associated with an increased risk of HF. � c 2004 Published by Elsevier Ltd on behalf of The European Society of Cardiology.

We compared the effects of 6 months administration of atenolol or nebivolol on resting and exercise hemodynamic parameters and maximal exercise capacity, in 26 patients with hypertension and left ventricular (LV) diastolic dysfunction (ejection fraction >50%, end-diastolic diameter

Heart failure (HF) is the final outcome of virtually all cardiovascular diseases and is a major and increasingly serious public health problem. The renin-angiotensin system plays an important role in the pathogenesis of cardiovascular disease. Insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) has attracted significant attention; it has been extensively investigated in a spectrum of cardiovascular phenotypes because of its correlation with serum ACE activity. There is controversy regarding the association of ACE I/D polymorphism with cardiovascular disease. The aim of this study was to investigate whether ACE genotype is associated with HF by comparing cases and controls. The study sample consisted of 229 cases with HF due to coronary heart disease or idiopathic dilated cardiomyopathy and 230 controls recruited from the general population. The ACE I/D genotype was identified using a polymerase chain reaction assay. No evidence was found to support an association between ACE genotype and HF.

Background We investigated whether off-pump coronary artery bypass (OPCAB) surgery should be the procedure of choice in total arterial myocardial revascularization with composite grafts. Methods We prospectively enrolled 176 patients undergoing total arterial myocardial revascularization and assigned them at random to one of two groups: group 1 was composed of 88 patients undergoing coronary surgery with cardiopulmonary bypass (CPB); group 2 consisted of 88 patients receiving the OPCAB procedure. We excluded from this study patients with significant risk factors for CPB-related morbidity. Composite arterial grafts in Y-T shape were realized in three different configurations according to patients' characteristics, coronary anatomy, and target stenosis. Results There were no significant differences between the two groups in terms of preoperative characteristics and risk factors (Euroscore: group 1=6.1 ± 3.5, group 2=6.6 ± 3.8). Mean number of anastomoses was similar in both groups (group 1=2.8 ± 0.8, group 2=2.7 ± 0.5) whereas mean mechanical ventilation time (group 1=23 ± 9 hours, group 2=9 ± 4 hours), intensive care unit stay (group 1=43 ± 6 hours, group 2=22 ± 8 hours), and postoperative stay (group 1=7 ± 3 days, group 2=5 ± 2 days) were significantly reduced in group 2. Early mortality was 2.3% in group 1 and 3.4% in group 2 ( p = not significant). Major postoperative complications occurred similarly in the two groups (atrial fibrillation: group 1=35.2%, group 2=21.6%; myocardial infarction: group 1=2.2%, group 2=1.1%; stroke: group 1=2.2%, group 2=0%; abdominal infarction: group 1=3.4%, group 2=0%). At follow-up (mean, 15 ± 12 months) no significant differences were observed in terms of survival free of any cardiac-related event (group 1=94.3%, group 2=96.5%; p = not significant). Conclusions Off-pump coronary artery surgery could be successfully used for total arterial grafting without compromising the completeness of revascularization. Avoidance of CPB significantly decreased mechanical ventilation support and length of intensive care unit and postoperative stay; however in the absence of risk factors for cardiopulmonary bypass, off-pump coronary artery surgery did not improve early and midterm clinical outcome.

Objectives The aim of this study was to evaluate the serum levels of carbohydrate antigen 125 (CA125) in patients with congestive heart failure (CHF). Background CA125 is a glycoprotein produced by serosal epithelium, found to be increased in ovarian cancer. Methods Serum levels of CA125 were obtained in 286 patients (122 males and 164 females; age 69 ± 13 years) with CHF (left ventricular ejection fraction 30 ± 11%). A non-invasive evaluation was obtained by Doppler echocardiography; right heart catheterization was performed in 88 patients. An attempt to adjust medical therapy to maximally tolerated doses was done, and CA125 was repeated after 18 days (range 7 to 40) in 80 patients. The mean follow-up duration was 6 ± 3 months in 240 patients. Results The mean value of CA125 was 68 ± 83 U/ml (range 3 to 537): 71 ± 85 in men and 56 ± 64 U/ml in women (p = NS). CA125 above the normal value ( 35 U/ml (p < 0.01). After medical treatment optimization, NYHA class decreased by more than one grade in 56 of 80 patients and was unchanged or increased in 24 patients: CA125 decreased from 125 ± 98 to 53 ± 61 U/ml (p < 0.001) in the former and changed from 130 ± 81 to 153 ± 61 U/ml (p = NS) in the latter. Conclusions Our data suggest that CA125 is related to CHF severity and short-term prognosis. Furthermore, fluctuations of CA125 serum levels over time may reflect changes induced by therapy. Therefore, measurements of CA 125 serum levels might be proposed for the serial assessment of CHF patients.

Objective Patients with severe heart failure, refractory to drug treatment, can be indicated for biventricular pacing, shown to be useful in overcoming the desynchronization of the ventricular contraction pattern, which generally worsens the hemodynamic conditions of such patients. This study was aimed at assessing 1) clinical effectiveness of conventional therapy compared with biventricular pacemaker; 2) hospital ward’s budget before and after device implantation.

Objectives We compared the hemodynamic effects of dobutamine and enoximone administration before and after long-term beta-blocker therapy with metoprolol or carvedilol in patients with chronic heart failure (HF). Background Patients with HF on beta-blocker therapy may need hemodynamic support with inotropic agents, and the hemodynamic response may be influenced by both the inotropic agent and the beta-blocker used. Methods The hemodynamic effects of dobutamine (5 to 20 μg/kg/min intravenously) and enoximone (0.5 to 2 mg/kg intravenously) were assessed by pulmonary artery catheterization in 29 patients with chronic HF before and after 9 to 12 months of treatment with metoprolol or carvedilol at standard target maintenance oral doses. Hemodynamic studies were performed after ≥12 h of wash-out from all cardiovascular medications, except the beta-blockers that were administered 3 h before the second study. Results Compared with before beta-blocker therapy, metoprolol treatment decreased the magnitude of mean pulmonary artery pressure (PAP) and pulmonary wedge pressure (PWP) decline during dobutamine infusion and increased the cardiac index (CI) and stroke volume index (SVI) response to enoximone administration, without any effect on other hemodynamic parameters. Carvedilol treatment abolished the increase in heart rate, SVI, and CI and caused a rise, rather than a decline, in PAP, PWP, systemic vascular resistance, and pulmonary vascular resistance during dobutamine infusion. The hemodynamic response to enoximone, however, was maintained or enhanced in the presence of carvedilol. Conclusions In contrast with its effects on enoximone, carvedilol and, to a lesser extent, metoprolol treatment may significantly inhibit the favorable hemodynamic response to dobutamine. No such beta-blocker–related attenuation of hemodynamic effects occurs with enoximone.

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

AIMS Heart failure is a widespread syndrome involving several organs, still characterized by high mortality and morbidity, and whose clinical course is heterogeneous and hardly predictable.In this scenario, the assessment of heart failure prognosis represents a fundamental step in clinical practice. A single parameter is always unable to provide a very precise prognosis. Therefore, risk scores based on multiple parameters have been introduced, but their clinical utility is still modest. METHODS In this review, we evaluated several prognostic models for acute, right, chronic, and end-stage heart failure based on multiple parameters. In particular, for chronic heart failure we considered risk scores essentially based on clinical evaluation, comorbidities analysis, baroreflex sensitivity, heart rate variability, sleep disorders, laboratory tests, echocardiographic imaging, and cardiopulmonary exercise test parameters. RESULTS What is at present established is that a single parameter is not sufficient for an accurate prediction of prognosis in heart failure because of the complex nature of the disease. However, none of the scoring systems available is widely used, being in some cases complex, not user-friendly, or based on expensive or not easily available parameters. CONCLUSION We believe that multiparametric scores for risk assessment in heart failure are promising but their widespread use needs to be experienced.