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Patients with advanced heart failure suffer from severe and persistent symptoms, often not responding disease-modifying drugs, a marked limitation of functional capacity and poor quality of life that can ameliorate with inotropic drugs therapy. In small studies, pulsed infusions of classical inotropes (ie, dobutamine and milrinone) are associated with improvement in hemodynamic parameters and quality of life in patients with advanced heart failure. However, because of the adverse effects of these drugs, serious safety issues have been raised. Levosimendan is a calcium-sensitizing inodilators with a triple mechanism of action, whose infusion results in hemodynamic, neurohormonal, and inflammatory cytokine improvements in patients with chronic advanced HF. In addition, levosimendan has important pleiotropic effects, including protection of myocardial, renal, and liver cells from ischemia-reperfusion injury, and anti-inflammatory and antioxidant effects; these properties possibly make levosimendan an "organ protective" inodilator. In clinical trials and real-world evidence, infusion of levosimendan at fixed intervals is safe and effective in patients with advanced HF, alleviating clinical symptoms, reducing hospitalizations, and improving the quality of life. Therefore, the use of repeated doses of levosimendan could represent the therapy of choice as a bridge to transplant/left ventricular assist device implantation or as palliative therapy in patients with advanced heart failure.

Beta-thalassemias are a group of inherited, autosomal recessive diseases, characterized by reduced or absent synthesis of beta-globin chains of the hemoglobin tetramer, resulting in variable phenotypes, ranging from clinically asymptomatic individuals to severe anemia. Three main forms have been described: heterozygotes, homozygotes β+, and homozygotes β°. Beta-thalassemia major (β-TM), the most serious form, is characterized by an absent synthesis of globin chains that are essential for hemoglobin formation, causing chronic hemolytic anemia. Cardiac complications represent a leading cause of mortality in β-TM patients, although an important and progressive increase of life expectancy has been demonstrated after the introduction of chelating therapies. Iron overload is the primary factor of cardiac damage resulting in thalassemic cardiomyopathy, in which diastolic dysfunction usually happens before systolic impairment and overt heart failure (HF). Although iron-induced cardiomyopathy is slowly progressive and it usually takes several decades for clinical and laboratory features of cardiac dysfunction to manifest, arrhythmias or sudden death may be present without signs of cardiac disease and only if myocardial siderosis is present. Careful analysis of electrocardiograms and other diagnostic tools may help in early identification of high-risk β-TM patients for arrhythmias and sudden cardiac death.

Infusions of levosimendan delivered in ambulatory/outpatient settings have been shown to improve quality of life and reduce hospitalizations in patients with advanced heart failure (HF). The aim of this pilot study was to evaluate the effects of ambulatory infusion of levosimendan on echocardiographic markers of perfusion, congestion, and cardiovascular efficiency. Thirty patients with diagnosed advanced HF underwent ambulatorial infusion of levosimendan at a total dose of 6.25 mg as a part of a repetitive biweekly treatment strategy with the inotrope. Standardized transthoracic echocardiography and Doppler examinations, were performed 1 hour before and 48 hours after completion of ambulatory infusion. At 48 hours after ambulatory infusion of levosimendan, a significant increase in the stroke volume (37.47 ± 12.38 mL/beat vs. 45.47 ± 14.48 mL/beat; P0.05) and cardiac output (2.64 ± 0.66 L/min vs. 3.26 ± 0.57 L/min; P0.05) occurred. Significant postreductions versus prereductions were also recorded in left atrial pressure (27.37 ± 6.62 mm Hg vs. 22.82 ± 4.17 mm Hg; P0.01), mean pulmonary artery pressure (27.69 ± 4.64 mm Hg vs. 23.24 ± 5.32; P0.01), and inferior vena cava diameter (23.81 ± 7.63 mm vs. 18.53 ± 4.82 mm; P0.01). Significant improvements were noted in the resting cardiac power output (0.46 ± 0.15 watt vs. 0.53 ± 0.22 watt; P0.01) and the resting cardiac power index (0.24 ± 0.08 watt/m2 vs. 0.28 ± 0.11 watt/m2; P0.01). In outpatients with advanced HF, infusion of levosimendan was associated with hemodynamic responses that may contribute to the clinical benefit previously reported in such patients.

Aims. The occurrence of ventricular arrhythmias (VAs) in ischemic heart disease (IHD) patients is related to the presence and extent of fibrotic/scar tissue. As coronary atherosclerosis is the underlying cause of myocardial ischemia and fibrosis, in IHD patients implanted with an implantable cardioverter defibrillator (ICD) we investigated the relation between the VA burden and the complexity of coronary atherosclerotic lesions. Methods and results. In IHD patients who underwent coronary angiography and ICD implant, the Syntax scores I and II (SSI-II), as index of the severity of the coronary atherosclerotic disease, and the occurrence of VA were assessed. Overall 144 patients were included (123 males). Of these 22 patients (15%) experienced at least one episode of VA (cycle length 298 ± 19 msec) that required ICD intervention. The number of episodes per patient and per year was 4 ± 6 and 2.8 ± 4, respectively. Patients that experienced a VA compared to those free from arrhythmic events did not have distinct baseline clinical characteristics except for a higher SS I and SS II (21 (IQR 13–38) vs. 16 (IQR 10–23), p = 0.037, and 50 (IQR 39–62) vs. 42 (IQR 34–50), p = 0.012). In the binary logistic regression analyses the SS I and II were the only independent predictors of VA occurrence. A higher SS II was also associated with an earlier time to first event (p = 0.005). Conclusion. Higher SS I-II scores reflect a more severe coronary atherosclerosis and are associated with a greater VA burden. Further studies are needed to better clarify the ability of SSI-II to stratify the risk of IHD patients to develop life-threatening VA.

Funding Acknowledgements Type of funding sources: None. Background Intermittent infusions of levosimendan in an outpatient setting have been associated with improved symptoms and reduced hospitalizations in patients with advanced heart failure (HF). Little is known on the potential effect of intermittent levosimendan infusions on right ventricle (RV)-pulmonary arterial (PA) coupling in ambulatory patients with advanced HF. Purpose Aim of the present study was to explore the effects of intermittent levosimendan infusions on the ratio between tricuspid annular plane systolic excursion (TAPSE) and pulmonary artery systolic pressure (PAPs), an echocardiographic measure of RV/PA coupling, in ambulatory patients with advanced HF, and on left ventricular arterial coupling (VAC), expressed as the relationship between arterial elastance (Ea) and ventricular elastance (Ees). Methods 17 ambulatory patients with advanced HF treated with intermittent levosimendan (6-hour intravenous infusion, 0.2 ug/kg/min without bolus) received baseline clinical, biochemical and echocardiographic evaluation and changes in TAPSE/PAPs ratio were assessed from baseline to 48 hours after the infusion, based on the pharmacokinetic profile of levosimendan. VAC, expressed as Ea/Ees ratio, was obtained by a calculator (iElastance) designed for non-invasive single beat measure of end-systolic Ees and Ea according to Chen"s method. Results After 48 hours from levosimendan infusion, there was a significant improvement of TAPSE/PAPs ratio (p = 0.04), stroke voume (SV) (p = 0.05) and cardiac output (CO)(p = 0.04). We observed a significant reduction of Ea (p = 0.007) and of Ees (p = 0.01) and a non significant improvement of VAC (p = 0.4)(Tab.1). Conclusion. Our results show that an intermittent 6-hour levosimendan infusion at 0.2 ug/kg/min improves after 48 hours RV-PA coupling, SV, CO, Ea and Ees in ambulatory patients with advanced HF. Further studies including more patients are necessary to confirm these preliminary findings. Tab.1 Baseline 48h afterlevosimendan infusion p value NT-proBNP (pg/mL) 5607 ± 4300 3868 ± 3856

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia and is frequently present in patients with mitral regurgitation (MR). Currently, there is a lack of real-world evidence specifically addressing the clinical performance of direct oral anticoagulants (DOACs) in patients with AF and concomitant MR. Therefore, the aim of the present study was to assess the efficacy and safety profile of DOACs therapy in patients with AF and MR. Methods: Data for this study were sourced from the Atrial Fibrillation Research Database in the Department of Cardiology at Monaldi Hospital. The database was queried for AF patients with MR who were prescribed DOACs therapy. The primary safety outcome was defined as the annual incidence rate of major bleeding events and the primary effectiveness outcome as the annual incidence rate of all events classified as ischemic stroke, transient ischemic attacks, and systemic embolisms. Results: Consecutive AF patients with concomitant mild to severe MR who received DOACs therapy (n = 259) were included. Patients were dichotomized in 2 groups according to MR severity: a mild-to-moderate group (MR 1-2+; n = 151) and a moderate-to-severe group (MR 3-4+; n = 108). The incidence rate of major bleedings was significantly higher in MR 3-4+ group (3.92%) compared with the MR 1-2+ group (1.18%; hazard ratio [HR]: 3.2; 95% CI: 1.4-7.3; P = .0059). The incidence rate of thromboembolic events between MR 3-4+ group (0.66%) and MR 1-2+ group (0.62%) was not significantly different (HR: 0.75; P = .823). Conclusions: In the present study, there was no difference in the efficacy profile of DOACs between AF patients with mild-to-moderate and moderate-to-severe MR. Considering the increased bleeding risk, a close and careful follow-up should be warranted for patients with moderate-to-severe MR.

Beta-blockers are essential drugs for the treatment of many cardiovascular diseases, such as heart failure, acute and chronic ischemic heart disease, tachyarrhythmias, and hypertension. However, these drugs have not been used in cardiac transplant patients for many years owing to the fear that they could reduce cardiac output and functional capacity. In recent years, however, some evidence has shown that even in cardiac transplanted patients, β-blockers are useful and effective in the treatment of sinus tachycardia, supraventricular and ventricular tachyarrhythmias, left ventricular systolic dysfunction, and arterial hypertension. Furthermore, some data have shown that the use of β-blockers is associated with reduced mortality in heart transplant recipients. In this review, we summarize this evidence with particular emphasis on the practical aspects of the use of β-blockers in post-transplantation patients to promote the use of this important class of drugs in clinical practice.

Diabetes mellitus (DM) is a chronic metabolic disease which is independently associated with unfavorable clinical outcomes in patients with atrial fibrillation (AF). Few real-world data are available about the clinical performance of non-vitamin K oral anticoagulants (NOACs) among patients with atrial fibrillation and diabetes. The aim of our propensity score-matched cohort study was to compare the safety and effectiveness of Edoxaban versus well-controlled vitamin K antagonists (VKAs) therapy among this population. In this study, we considered patients with AF and diabetes on Edoxaban or VKAs therapy included in the multicenter Atrial Fibrillation Research Database (NCT03760874). The occurrence of major bleedings (MB) and thromboembolic events (a composite of ischemic stroke, transient ischemic attack, systemic embolism) was respectively considered primary safety and effectiveness outcome. We identified 557 AF patients with diabetes who received Edoxaban (n: 230) or VKAs (n: 327) treatment. After propensity score matching analysis, 135 Edoxaban and 135 VKA recipients with similar clinical characteristics were evaluated. The mean follow-up was 27 &plusmn, 3 months. The incidence rate of thromboembolic events (TE) was 3.0 per 100 person-years (1.11 in Edoxaban vs. 1.9 in the VKA group, hazard ratio (HR): 0.59, 95% confidence interval (CI), 0.14 to 2.52, p = 0.48). The incidence rate of major bleedings (MB) was 3.7 per 100 person-years (1.2 in Edoxaban vs. 2.7 in the VKA group, HR: 0.43, 95% CI, 0.10 to 1.40, p = 0.14). The incidence rate of intracranial hemorrhage was 0.35 per 100 person-years in Edoxaban vs. 0.74 in the VKA group (HR: 0.49, 95% CI: 0.05 to 5.54, p = 0.56). A positive net clinical benefit (NCB) of Edoxaban over VKAs was found (+1.39). Insulin therapy (HR: 1.76, p = 0.004) and glycated hemoglobin (HR: 1.17, p = 0.002) were found to be independent predictors of TE, moreover, the concomitant use of antiplatelet drugs (HR: 2.41, p = 0.001) was an independent predictor of MB. Conclusions: Our data support the hypothesis of the safety and efficacy of Edoxaban for use in patients with AF and diabetes, justified by a favorable NCB over VKAs.

Funding Acknowledgements none Background In degenerative mitral regurgitation (DMR), left ventricle (LV) and left atrium (LA) undergo progressive volume overload leading to chamber remodelling and dysfunction in advanced stages. Speckle tracking echocardiography (STE) is an estabilished technique able in detecting subclinical LA and LV dysfunction in this setting. However data are lacking on the relationship of LA and LV function in DMR patients. Purpose Our aim was to assess LA function in patients with DMR and to explore its possible correlations with LV dimensions and systolic function. Methods We enrolled 95 patients with mild to severe DMR, dichotomizing them on the basis of mitral regurgitation severity (DMR 1-2: mild and mild-to-moderate MR; DMR 3-4: at least moderate to severe MR). LA function was assesed with 2D speckle tracking echocardiography. Results The two groups were well matched. DMR 3-4 group (n= 48) showed higher LA and LV volumes, lower right ventricle longitudinal systolic function and higher values of systolic pulmonary pressure. There was not significant difference in LV ejection fraction (LVEF) and global longitudinal strain (GLS). Among LA function indexes, only peak systolic reservoir strain was significantly reduced in DMR 3-4 group (21,9± 6,2% vs 24,7± 7,2% ; p= 0,04). Then population study was further divided in two groups according to the presence (LA dys+) or absence (LA dys-) of LA dysfunction, defined as reservoir strain values below the median [median 23.7%; LAdys- group (n. 49), LAdys+ group (n.46) ]. At the comparison of continuous variables (Tab.1), LAdys+ group showed larger LV end systolic diameter and more impaired LVEF (60,9± 9,8% vs 65,4± 4,8%; p: 0,004) and GLS (20,04 ± 3,7% vs 23,53 ± 2,7%; p Conclusions Our data showed that LA reservoir strain was impaired in patients with moderate to severe DMR. Furthermore, patients with LA dysfunction showed reduced LVEF and GLS values. Consequently, LA dysfunction assessed with STE may be a novel marker of early LV systolic dysfunction in patients with degenerative mitral regurgitation. Tab.1 LAdysf- (n = 49) LAdysf+ (n = 46) P value LVESD (mm) 31.78 ± 4.1 34.74 ± 7.6 0.020 LAVI (mL/mq) 44.5 ± 15.1 55.6 ± 25.6 0.015 TAPSE (mm) 26.30 ± 3.96 24.02 ± 3.31 0.004 sPAP (mmHg) 31.4 ± 7.0 36.4 ± 10.9 0.009 LVEF (%) 65.4 ± 4.8 60.9 ± 9.8 0.004 GLS (%) 23.5 ± 2.7 20.0 ± 3.7

Funding Acknowledgements none Background The distinction between proportionate and disproportionate functional mitral regurgitation (FMR), based on the relationship between effective regurgitant orifice area (EROA) and left ventricle end diastolic volume (LVEDV), has recently been proposed as a possible new clinical and physiopathological framework to identify patients that could likely benefit from transcatheter mitral repair. Purpose The aim of our study was to explore the possible prognostic implications of the EROA/LVEDV ratio in patients with FMR treated with MitraClip. Methods – Baseline EROA/LVEDV was calculated in 137 patients with at least moderate-to-severe, symptomatic FMR treated with MitraClip. All patients underwent clinical, biochemichal and echocardiographic evaluation before MitraClip. EROA was calculated using PISA method. The primary outcome was a composite end-point of all-cause death or re-hospitalization for heart failure (HF). Results – The median follow-up was 1.1 years. The primary outcome occurred in 59 patients (43 %). Population study showed a LVEDVi 113.52± 32.16 mL/m2, LVEF 29.75± 10.06% and EROA 39.45± 15.43 mm2.. The cut-off value of EROA/LVEDV ratio for primary outcome, identified by receiver operating characteristic curve, was 0.15 (AUC 0,65, p = 0.002) with a sensitivity and specificity of 78% and 52%, respectively. Patients were divided in two groups according to the identified cut-off. Patients with higher ratio (Group I, n = 88) presented a less dilated LV (LVEDVi: 105.1 ± 29.6 mL/m2 vs 128.2 ± 31.9 mL/m2, p < 0.001; LVESVi: 73.1 ± 27.7 mL/m2 vs 94.9 ± 29.05 mL/m2, p < 0.001), and a more severe MR (EROA: 47.9 ± 12.1 mm2 vs 25.1 ± 8.3 mm2, p < 0.001; vena contracta: 7.2 ± 1.3 mm vs 6.5 ± 1.3 mm, p = 0.008). There were no significant differences of left ventricle ejection fraction, right ventricle systolic function and systolic pulmonary pressure between the groups. At univariate analysis, EROA/LVEDV ratio >0.15 (HR = 2.223, 95% CI 1.121-4.411, p = 0.022), baseline evidence of atrial fibrillation (HR = 1.949, 95% CI 1.156-3.283, p = 0.012) and baseline pro-BNP (HR= 1.000, 95% CI 1.000-1.000, p = 0,001) were associated with a worse clinical outcome. At multivariate Cox-regression analysis, both EROA/LVEDV ratio >0.15 and baseline pro-BNP values were identified as independent predictors (HR 2.941, 95% CI 1.035-8.353, p = 0.043; HR = 1.000, 95% CI 1.000-1.000, p = 0.002, respectively). At Kaplan-Meier survival analysis, patients with EROA/LVEDV >0.15 had a significant lower freedom from composite endpoint (log-rank χ2 =5.517, p= 0.019; Fig. 1). Conclusion Our data show that EROA/LVEDV ratio was an independent predictor of adverse clinical outcome in FMR patients treated with MitraClip. This preliminary experience shows that this index could help to identify subgroups of patients with potential different clinical benefits from Mitraclip therapy. However, further and extended data are needed to provide more precise evidence. Abstract 428 Figure. Fig. 1

Cardiotoxicity related to antineoplastic agents is a rising and growing issue, therefore early recognition and prompt management can impact on the overall prognosis of cancer patients. We report the case of a 70-year-old woman without cardiovascular risk factors, with a medical history of non-Hodgkin lymphoma and chronic myeloid leukemia treated with chemotherapy and radiotherapy, who underwent transcatheter aortic valve replacement for severe aortic stenosis and cardiac resynchronization therapy for further development of complete left bundle branch block, with a significant improvement of her functional status and left ventricle systolic function in a long-term follow-up.

Background: right ventricle-pulmonary artery (RV-PA) coupling assessed by measuring the tricuspid anular plane systolic excursion (TAPSE)/pulmonary artery systolic pressure (PASP) ratio has been recently proposed as an early marker of right ventricular dysfunction in patients with heart failure with a reduced ejection fraction (HFrEF). Methods: As the effects of sacubitril/valsartan therapy on RV-PA coupling remain unknown, this study aimed to analyse the effect of this drug on TAPSE/PASP in patients with HFrEF. We retrospectively analysed all outpatients with HFrEF referred to our unit between October 2016 and July 2018. Results: At the 1-year follow-up, sacubitril/valsartan therapy was associated with a significant improvement in TAPSE (18.26 &plusmn, 3.7 vs. 19.6 &plusmn, 4.2 mm, p &lt, 0.01), PASP (38.3 &plusmn, 15.7 vs. 33.7 &plusmn, 13.6, p &lt, 0.05), and RV-PA coupling (0.57 &plusmn, 0.25 vs. 0.68 &plusmn, 0.30 p &lt, 0.01). These improvements persisted at the 2-year follow-up. In the multivariable analysis, the improvement in the RV-PA coupling was independent of the left ventricular remodelling. Conclusions: in patients with HFrEF, sacubitril/valsartan improved the RV-PA coupling, however, further trials are necessary to evaluate the role of sacubitril/valsartan in the treatment of right ventricle (RV) dysfunction either associated or not associated with left ventricular dysfunction.

The purpose of the current study was to compare the efficacy and safety of edoxaban versus vitamin K antagonist (VKA) therapy among a cohort of elderly patients (ie, those aged ≥75 years) with atrial fibrillation (AF) in a real-life setting.A propensity score-matched cohort observational study was performed comparing the safety and efficacy of edoxaban versus VKA therapy among a cohort of elderly (aged ≥75 years) patients with AF in a real-life setting. Follow-up data were obtained through outpatient visits at 1, 3, and every 6 months. The primary safety outcome was major bleeding. The primary efficacy outcome was the composite of stroke, transient ischemic attack, and systemic embolism.A total of 130 patients receiving edoxaban 60 mg (EDO) treatment were compared with the same number of VKA recipients. The mean follow-up was 16 (2.6) months. The cumulative incidence of thromboembolic events in the EDO and VKA groups was 1.5% (2 of 130) and 2.3% (3 of 130), respectively (P 0.6). The cumulative incidence of major bleeding events was 1.5% (2 of 130) in the EDO group and 3.1% (4 of 130) in the VKA group (P 0.4). The total anticoagulant therapy discontinuation rate was 2.3% (3 of 130) in the EDO group and 4.6% (6 of 130) in the VKA group (P 0.3). A nonsignificant trend in improved adherence was observed between the EDO and VKA groups (81% vs 78%; P = 0.6).Edoxaban therapy showed a good real-life performance among elderly patients (aged ≥75 years) with AF.

One of the major complications of radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF) is pulmonary vein stenosis (PVS). The natural history of PVS, especially when it involves more than one vein, leads to severe and irreversible pulmonary hypertension with end-stage right heart failure that can require, in extreme cases, even heart-lung transplantation. We report the case of a young patient who underwent RFCA for a single lasting episode of AF and developed PVS years later. He was treated with ballon venoplasty followed by stent implantation in left pulmonary vein because of PVS relief. This reported case emphasizes the need of an adequate indication for RFCA for AF, considering the benefit-risk ratio especially in young patients with normal cardiac function.

A 63-year-old man with a past medical history of ischemic cardiomyopathy and multiple heart failure hospitalizations was admitted to our Institute for worsening exertional dyspnea (New York Heart Association functional class III). Transesophageal echocardiography revealed severe left ventricular (LV

In this controlled trial, 30 elderly patients with congestive heart failure, New York Heart Association (NYHA) classes II and III, were randomly assigned to treatment with captopril 25 mg three times daily or delapril 15 mg twice daily. At the end of an 8-week treatment period, clinical symptoms of heart failure were significantly relieved by both drugs, with a consistent and statistically significant improvement in patients' quality of life evaluated using a symptoms/activity scale (p0.001). None of the patients was judged NYHA class III at the end of the trial and 40% were assigned to class I (p0.01). There was a relevant, but not statistically significant, increase in exercise duration in both treatment groups (10% captopril group, 14% delapril group), but the number of patients discontinuing the exercise test for dyspnea was 50% less in the delapril group. Neither drug had evident effects on echocardiographic left ventricular parameters. Two patients treated with captopril and 3 with delapril complained of mild-to-moderate adverse reactions. The safety of both drugs was confirmed by laboratory tests.