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Two-dimensional strain echocardiography (2D-SE) is a reliable method for measuring deformation of the left ventricle.Aim of the study was to determine changes in 2D-SE parameters over time collected during dipyridamole stress echo-cardiography (dipy-stress) and prognosis of patients with non-diagnostic dipy-stress results.In the first phase of the study, assessment of a prospective enrolled population with a non-diagnostic dipy-stress test result was conducted, checking through coronary CT angiography (CCTA) the presence of coronary artery disease (CAD). In the follow-up phase, an echocardiographic re-evaluation and outcome analysis during a mean follow-up of 78 months was carried out.In the first phase, Global Circumferential Strain (GCS) values were similar in the CCTA positive and CCTA negative groups at rest and after stress. For Global Longitudinal Strain (GLS), there was a significant reduction (p.0001) in the CCTA positive group compared to the CCTA negative group. After 78 ± 9 months none of the enrolled patients experimented cardiac events. Values of GCS, both at rest and after stress, did not differ statistically comparing follow-up values with baseline ones. No statistically significant changes were seen in the same analysis for GLS rest and stress values, between baseline and follow-up in the two groups.Performing 2D-SE during dipy-stress can detect mild CAD that conventional stress-tests miss. Patients with mild coronary stenosis may have a favorable mid-term prognosis, but efforts should be made to investigate the decrease trend in GLS, at rest and after stress, reported in this patient group.

Background: The prognostic role of moderate hyperkalemia in reduced ejection fraction (HFrEF) patients is still controversial. Despite this, it affects the use of renin–angiotensin–aldosterone system inhibitors (RAASi) with therapy down-titration or discontinuation. Objectives: Aim of the study was to assess the prognostic impact of moderate hyperkalemia in chronic HFrEF optimally treated patients. Methods and results: We retrospectively analyzed MECKI (Metabolic Exercise test data combined with Cardiac and Kidney Indexes) database, with median follow-up of 4.2 [IQR 1.9–7.5] years. Data on K+ levels were available in 7087 cases. Patients with K+ plasma level ≥ 5.6 mEq/L and < 4 mEq/L were excluded. Remaining patients were categorized into normal >4 and < 5 mEq/L (n = 4826, 68%) and moderately high ≥5.0 and ≤ 5.5 mEq/L (n = 496, 7%) K+. Then patients were matched by propensity score in 484 couplets of patients. MECKI score value was 7% [IQR 3.1–14.1%] and 7.3% [IQR 3.4–15%] (p = 0.678) in patients with normal and moderately high K+ values while cardiovascular mortality events at two years follow-up were 41 (4.2%) and 33 (3.4%) (p = 0.333) in each group respectively. Conclusions: Moderate hyperkalemia does not influence patients' outcome in a large cohort of ambulatory HFrEF patients.

Background and aims Takotsubo syndrome (TTS) is an acute heart failure syndrome featured by a reversible left ventricular systolic dysfunction. However, few data have been reported about prevalence of non-cardiovascular comorbidities as chronic neurological disorders in TTS patients. Aim of this study was to compare clinical features, short- and long-term outcome among TTS patients with history of neurological disorder. Methods 2301 patients with TTS were enrolled in a multicenter prospective European registry from July 2002 to November 2021. Clinical features, in- and out-of-hospital MACE, laboratory and imaging data were collected and a long-term follow-up was performed. Results Prevalence of history of neurological disorder was 17% (n= 400 pts). Most represented neurological conditions were previous cerebrovascular disorders (ischemic stroke and transient ischemic attack, 36.2%), followed by neurodegenerative disorders (30.7%, including cognitive disorders and motion disorders), tensive migraine (10%) and epilepsy (9.5%). Neurological Patients developed TTS more frequently after a physical trigger (46.2% vs 33.8%, p During hospitalization neurological patients had longer in-hospital stay (10±11 days vs 8±8 days, p Long-term mortality was higher in patients with history of neurological disorders (23.5% vs 10%, p Conclusions Patients with history of neurological disorders and TTS have different clinical features and worse prognosis with higher short-term and long-term mortality.

Background Systemic sclerosis (SSc) is a connective tissue disease characterized by the fibrosis of skin and internal organs, frequent immunity abnormalities and alterations in microvasculature. Among SSc complications, Pulmonary Hypertension (PH) is a frequent and severe one. Many echocardiographic parameters are used to assess pulmonary pressure and Right Ventricle (RV) dimension and function in these patients, from classical echocardiographic indexes to the most recent Speckle-Tracking Echocardiography (STE), while flow-mediated vasodilation (FMD) is the most common method to assess vascular reactivity. Aim of the study To evaluate any possible relations between endothelial function and RV dimension and function in patients with SSc. Method 48 sclerodermic patients underwent to echocardiographic examination and FMD, searching for relations between RV dimension and function and endothelial function indexes. For the RV we considered: 1) the eccentricity index (EI), 2) the fractional area change (FAC), 3) the ratio TAPSE/PAPs, 4) the RV basal diameter, 5) the RV free-wall strain and 6) the tricuspid regurgitation velocity; for the endothelium we evaluated the absolute difference between the radial artery diameters before and after 5 minutes of ischemia. We used a t-Student test (t-test) for unpaired samples with similar variances to verify the hypothesis that patients with altered RV parameters show a lower value in the absolute difference between radial diameters. Results Only EI and endothelial function showed a significant relation. In fact, with a level of confidence of the 95% we can say that patients with an EI>=1,1 report a minor increase in radial artery diameter than patients with EI Conclusions In patients affected by SSc, the endothelial function is related to eccentricity index. Multicenter studies are needed in order to confirm the results of our study

Background Takotsubo syndrome (TTS) is an acute heart failure syndrome featured by a reversible left ventricular systolic dysfunction with significant rate of in- and out-of-hospital mayor cardiac adverse events (MACE). Aim of the study To evaluate the possible role of hypochloremia as prognostic marker at short- and long-term follow-up in subjects with TTS. Methods 305 consecutive patients were enrolled in a multicenter international registry. Clinical, laboratory and echocardiographic evaluations were performed at admission and during hospitalization. Incident hypochloremia (serum chloride level below 97 mEq/l) during hospitalization was recorded. In-hospital MACE, short- and long-term mortality was recorded. Results Mean admission serum chloride levels were 102±5 mEq/l. 97 out of 305 (37%) patients experienced incident hypochloremia. Patients with incident hypochloremia were older (78±10 vs 73±12 years, p=0.01), had lower admission LVEF (34±8% vs 37±8%, p=0.009), and longer hospital stay (9±4 vs 7±4 days, p=0.0003). During hospitalization patients with incident hypochloremia had higher rates of complication (45% vs 32%, p=0.01), lower levels of natremia and azotemia at admission and discharge. At long term follow-up incident hypochloremia was associated with increased risk of MACE (49% vs 32%, p=0.005) and death (42% vs 24%, p=0.002, log rank p Conclusion Incident hypochloremia is a common finding among hospitalized patients with TTS, associated with higher risk of in-hospital events and long-term MACE and death.

Background Sodium glucose cotransporter type 2 inhibitors (SGLT2i), also called gliflozins, are playing an emerging role for the treatment of heart failure with reduced left ventricle ejection fraction (HFrEF). However, the direct effects of SGLT2i on left and right ventricular remodeling and function have not been completely clarified. We therefore aimed to assess clinical response to gliflozins focusing on echocardiographic evaluation and identify any predictive factors with a machine learning approach. Methods Based on Random Forest, a robust and consolidated machine learning approach, we carried out a single subject analysis to evaluate to which extent patients treated with gliflozins can effectively be distinguished from patients undergoing non-gliflozins treatments. Besides, we carried out an eXplainability analysis using Shapley values to outline the clinical parameters which mostly took advantage by gliflozins. Finally, machine learning experiments were designed to highlight the presence of specific clinical patterns undermining the gliflozins effectiveness. Results 5-fold cross-validation analyses showed that gliflozin treatment was identified with a 0.70 ± 0.03% accuracy; the most important parameters supporting such accuracy were Right Ventricle S’ Velocity (RV S’), Left Ventricle End Systolic Diameter (LVESD) and E/e’ ratio. Low Tricuspid Annular Plane Systolic Excursion (TAPSE) values along with high LVESD and End Diastolic Volume (EDV) values are likely to impair the gliflozin effectiveness. Conclusions Treatment with gliflozins resulted in an improvement of several echocardiographic parameters related to biventricular function and left ventricle remodeling. Several clinical parameters, as simple echocardiographic parameters, may accurately predict the cardiovascular response to gliflozins treatment.

Rationale Demographic characteristics of pulmonary arterial hypertension (PAH) patients have changed over time, but the effects of cardiovascular risk factors on risk status and pulmonary vascular resistance (PVR) reduction with initial oral combination therapy are not known. Therefore, we tested the relevance of cardiovascular comorbidities in this setting. Methods The study enrolled 181 treatment-naive PAH patients with a 6- months (IQR 144-363 days) right heart catheterization and risk assessment after initial oral combination therapy. Results Group-A, 96 (53.0%) patients without cardiac comorbidities; Group-B, 54 (29.8%) patients with one cardiac comorbidity; Group-C, 31 (17.1%) patients with ≥2 cardiac comorbidities. Group-C patients were older with a balanced gender distribution. There was a significant difference in PVR reduction moving from the absence to one or ≥2 cardiac comorbidities, respectively, median -45.0%, -30.3%, -24.3%. A ERS/ESC low-risk status was present at first follow-up in 50 (52.0%) patients in Group-A, 19 (35.1%) in Group-B, and 9 (29.0%) in Group-C; a REVEAL 2.0 low-risk status was present at first follow-up in 41 (42.0%) patients in Group-A, 15 (27.7%) in Group-B, and 7 (22.6%) in Group-C. Group-A patients were 2.3 times more likely to achieve/maintain a low risk status compared with Group-B and -C (OR 2.27, 95% C.I. 1.15-4.54, p=0.02). No significant difference was observed between patients with non-cardiac comorbidities and those without comorbidities. Conclusion Initial oral combination therapy seems associated with a less effective response for patients with cardiovascular comorbidities compared with the others, related to the magnitude of treatment- induced decrease in PVR.

Background Chronic heart failure (CHF) is characterized by endothelial dysfunction (ED). Sodium-glucose cotransporter type 2 inhibitors (SGLT-2i) represent a unique class of anti-hyperglycemic agents for type 2 diabetes mellitus (T2DM) that selectively inhibit renal glucose reabsorption, thereby increasing urinary excretion of glucose. Several studies have demonstrated the cardioprotective effects of SGLT-2i in patients with heart failure (HF), unrelated to its glucosuric effect. Nevertheless, it is unclear whether the benefits of SGLT-2i therapy also rely on the endothelial function in patients with CHF. Aim of the study To evaluate the effect of SGLT-2i on endothelial function through flow-mediated dilatation (FMD) in patients with CHF at baseline and after 3 months. Design and Methods EFI-CHF is a multi-center, prospective study that will evaluate the effect of SGLT-2i on endothelial function in patients with chronic stable heart failure across the left ventricular ejection fraction (LVEF) spectrum. Patients with NYHA class II/III symptoms, eGFR> 25 mL/min/1.73 m2, age >18 years will be enroll. Exclusion criteria are type 1 diabetes mellitus (T1DM), previous amputation surgery, recurrent urinary tract infections. For each patient medical history, clinical and biochemistry data will be collected. Starting treatment with SGLT2 inhibitors will be included. All patients will undergo FMD in an ambulatory setting, at time of enrolment and after 3 months of begin of study. Results The primary endpoint will be the improvement of endothelial function as assessed by FMD. An univariate and multivariate analysis will be performed to search for predictors of improvement of endothelian function. Conclusions The EFI-CHF will determine whether SGLT2i therapy improves endothelian function in patients with CHF starting SGLT2i therapy.

Background Pulmonary arterial hypertension (PAH) is a progressive and severe rare disease. It is a pulmonary vasculature obstructive disease that leads to right heart failure and death. Pulmonary circulation dysfunction endotelial is characterized by vasoconstriction and proliferation. Aim of study to search possible correlations between peripheral endothelian function and cardiopulmonary function in patients with suspect PAH. Materials Between February 2021 and May 2022, consecutive patients with suspect PAH underwent to assessment of peripheral endotelial function by FMD before of right heart catheterization and cardiopulmonary exercise testing. Results 46 patients (22 male, 67,9 ± 10,4 years old) with pulmonary hypertension were enrolled in the study. The following correlations were found between stress-resting absolute difference and % difference radial diameter: ramp (r: 0,69; p: 0,003 and r: 0,54; p: 0,028, respectively), Watt_AT (r: 0,63; p: 0,01 and r: 0,54; p: 0,03, respectively) and WATT_peak (r: 0,64, p: 0,009). Conclusions peripheral endothelial function may be related to funtional capacity in patients affected by pulmonary hypertension.

Background Cardiac remodelling is an adverse phenomenon linked to heart failure progression. Cardiac remodelling could represent the real therapeutic goal in the treatment of patients with heart failure with reduced ejection fraction (HFrEF), being potentially reversed through different pharmacotherapies. Currently, there are well-established drugs such as angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers and β-blockers with anti-remodelling effects; recently, angiotensin receptor neprilysin inhibitor effects on inhibiting cardiac remodelling were demonstrated. Benefits of gliflozins on left ventricular hypertrophy, dilation, and systolic and diastolic function were also described. Aim of study to evaluate possible echocardiographic differences between patients with HFrEF in treatment with ARNI or SGLT2I and patients with HFrEF in therapy with ARNI plus SGLT2i. Materials Between June 2021 and April 2022, consecutive patients with HFrEF underwent to conventional and advanced echocardography (TDI, 2DSTE). After 3 month, these patients underwent to echocardiographic follow-up. Results 76 patients (68 male, 66,51±9,68 years old) with HFrEF were enrolled in the study. After 3 month of therapy, there was an inverse relation between number of HFrEF drugs (0, 1 or 2) and echocardiographic parameters [E/E’ (r: -0,28; p: 0,036) and E/A (r: -0,37; p: 0,012)]. Conclusions About cardiac remodelling, there are not significant echocardiographic differeces but a better trend for the diastolic dysfunction in patients with HFrEF in treatment with ARNI plus SGLT2i vs HFrEF patients in therapy with ARNI or SGLT2i was showed.

Therapy based on disease-modifier drugs is among the required criteria to diagnose advanced heart failure (AdvHF). Nevertheless, several conditions, such as hospitalization, hypotension, renal dysfunction, electrolyte abnormalities, medical inertia, and patients' adherence, can make the maintenance of optimal medical therapy in patients with AdvHF challenging. Moreover, in recent years, new classes of drugs able have been shown to be able to further modify the natural history of heart failure with reduced ejection fraction, but they are still not widely adopted. This article discusses the optimal use of disease-modifier drugs in patients with AdvHF as well as the possible usefulness of the new therapeutic opportunities.

Purpose The use of sodium-glucose-cotransporter-type-2 inhibitors (SGLT2i) was associated in previous studies with an improved vascular function in non-human experimental models. We therefore sought to evaluate possible changes in endothelial function assessed by flow-mediated dilation (FMD) in patients with chronic heart failure (CHF) and type-2 diabetes mellitus (T2DM), switching from other oral hypoglycemic agents to SGLT2i in an observational study. Methods Twenty-two consecutive outpatients with CHF and T2DM were enrolled after switching to SGLT2i therapy, and compared with 23 consecutive controls from the same registry comparable for principal clinical characteristics. In all patients, endothelial function was assessed by FMD at baseline and after 3 months of follow-up. Results Three months of therapy with SGLT2i were associated with a statistically significant improvement in endothelial function (19.0 ± 5.7% vs 8.5 ± 4.1%, p p Conclusions Switch to SGLT2i in patients with CHF and T2DM was associated in an observational non-randomized study with an improved endothelial function.

Aims: Sacubitril/valsartan has changed the treatment of heart failure with reduced ejection fraction (HFrEF), due to the positive effects on morbidity and mortality, partly mediated by left ventricular (LV) reverse remodelling (LVRR). The aim of this multicenter study was to identify echocardiographic predictors of LVRR after sacubitril/valsartan administration. Methods and results: Patients with HFrEF requiring therapy with sacubitril/valsartan from 13 Italian centres were included. Echocardiographic parameters including LV global longitudinal strain (GLS) and global peak atrial longitudinal strain by speckle tracking echocardiography were measured to find the predictors of LVRR [=LV end-systolic volume reduction ≥10% and ejection fraction (LVEF) improvement ≥10% at follow-up] at 6month follow-up as the primary endpoint. Changes in symptoms [New York Heart Association (NYHA) class] and neurohormonal activations [N-terminal pro-brain natriuretic peptide (NT-proBNP)] were also evaluated as secondary endpoints; 341 patients (excluding patients with poor acoustic windows and missing data) were analysed (mean age: 65±10years; 18% female, median LVEF 30% [inter-quartile range: 25-34]). At 6month follow-up, 82 (24%) patients showed early complete response (LVRR and LVEF≥35%), 55 (16%) early incomplete response (LVRR and LVEF&nbsp

For decades, cardiologists have largely underestimated the role of the right heart in heart failure due to left heart disease. Nowadays, the importance of evaluating right ventricular (RV) structure and function in left heart failure is well documented and this concept has been emphasized in the most recent heart failure guidelines. However, several relevant questions remain unanswered such as the following: (a) which imaging technique (standard or 3D echocardiography or strain imaging or cardiac magnetic resonance) and, more, which parameters should be used to grade the severity of RV dysfunction? (b) do less widespread and less applied diagnostic tools such as cardiopulmonary stress testing and bioelectrical impedance analysis play a role in this field? (c) are there specific biochemical aspects of RV failure? (d) why notion of pathophysiology of heart and lung interaction are so well appreciated at an academic level but are not applied in the clinical setting? The present review has been prepared by the Heart Failure (HF) working group of the Italian Society of Cardiology and its main objective is to improve our understanding on RV dysfunction in heart failure.

Telemedicine may be of benefit in patients with heart failure (HF), although virtual visits are often carried out on an ad hoc basis. Herein, we discuss a structured protocol that defines all the steps needed for virtual visits, LEAP Virtual Visit, which includes guides and support kits for clinicians and patients.A working group of clinicians was established to develop a protocol for virtual visits. The virtual model for monitoring HF patients was based on measurement and sizing of patient flows, type of services, and critical organizational points. The process of virtual visits was broken down to identify the specific activities, players, roles, and support tools needed for implementation in daily practice.In the protocol developed, sections were included on patient eligibility, exams, supportive tools, and practical organizational aspects. IT requirements were also considered and the most widely used teleconference platforms were compared according to features that were considered to be priority for virtual visits. Protocols and support kits were developed, including guides for clinicians and patients, two questionnaires to assess the level of satisfaction, patient diary, disease awareness brochure, and template to monitor key performance indicators. The phases include an enrolment phase, document sharing phase, pre-evaluation phase, the virtual visit itself, and the post-visit phase. The protocol for the virtual visit was divided into 8 sequential steps to be carried out between the clinic and patient/caregiver.The protocol described can be expected to have a number of benefits for the patient, clinic, and healthcare structure.

Background Despite the use of optimal medical therapy, HFrEF remains a leading cause of morbidity, mortality and health care costs. The introduction of angiotensin receptor/neprilysin inhibitors (ARNIs) had a revolutionary impact on the treatment of patients with heart failure and reduced left ventricular ejection fraction (HFrEF). Methods The aim of the study was to monitor over time the perceived quality of life, the physical performance, the trend of BNP and NT-ProBNP and the NYHA functional class in patients with HFrEF during treatment with sacubitril/valsartan. We enrolled 37 patients (63 ± 10 years old, 76% men) who underwent a total of one year follow-up. All patients underwent clinical evaluation, 6MWT, blood analysis (in particular NT-pro-BNP and BNP, renal function test); Kansas City Cardiomyopathy Questionnaire (KCCQ) and the NYHA functional class assessment were also performed, at the beginning of the study and after 3, 6 and 12 months of therapy. Results We observed at each follow-up a significant improvement of KCCQ score, 6MWT, NTProBNP, BNP and of NYHA class. However, analyzing the Δ % of variation of each single parameter, the improvement was not uniform in time. We also observed that only 37% of patients tolerated the full recommended dose of sacubitril/valsartan (97/103 mg b.i.d.); of the remaining, 40% tolerated the intermediate dose (49/51 mg b.i.d.) and 23% the minimum (24/26 md b.i.d.). Conclusions Sacubitril/valsartan therapy improves significantly quality of life, physical effort resistance, BNP and NT-ProBNP and NYHA functional class in patients with HFrEF. Although not all the patients tolerated the maximum recommended dose, the beneficial effects were significant even at lower doses.

Left ventricular (LV) remodelling is a major mechanism underlying disease progression in patients with heart failure (HF) with reduced ejection fraction (EF). Previous studies that LVEF improvement and reverse remodelling can be achieved after therapy with Sacubitril/Valsartan in real-world settings. Therefore, we sought to investigate possible predictors of LV remodelling, in particular echocardiographic parameters derived by Tissue Doppler Imaging.Patients with chronic HF, LV dysfunction (EF35%), NYHA class II-III were followed up between September 2016 and January 2019. All patients underwent clinical and echocardiography follow up at baseline and after 12 months of therapy with sacubitril/valsartan.Fifty-four consecutive outpatients were enrolled in the study. At follow-up visit LVEF (38 ± 9 vs. 30 ± 5%,Treatment with sacubitril/valsartan in patients with systolic dysfunction is associated with an improvement in LVEF in a real world scenario. Smaller LV volumes are associated with better reverse LV remodelling.

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.

Purpose of Review Over the last decades, several classes of drugs have been introduced for the treatment of patients with heart failure with reduced ejection fraction (HFrEF). Their use has been supported by randomized controlled trials that have demonstrated improved patient outcomes. However, these trials enrolled a small number of female patients and sometimes have reported gender-related differences regarding the efficacy of the treatments. The aim of this review is to revise the available data about the influence of gender on the optimal treatment and drug dose in patients with HFrEF. Recent Findings Several gender-related differences in terms of pharmacokinetic and pharmacodynamic characteristics of the drugs have been described. These characteristics could be responsible for a different response and tolerability in men and women also when current recommended treatment of HFrEF is considered. Some studies have shown that, in women, lower doses of beta-blockers and inhibitors of renin angiotensin aldosterone system could be equally effective than higher doses in men, whereas sacubitril/valsartan could exert its favorable effect at greater values of left ventricular ejection fraction. Summary Although there is evidence about differences in the response to treatment of HFrEF in men and women, this has not been sufficient for differentiating current recommended therapy. Further studies should better clarify if the treatment of HFrEF should be based also on the patients’ gender.

Heart failure is a complex syndrome affecting several organs including kidney, lungs, liver, brain muscles and sympathetic system. Each of these organs might contribute to its severity and prognosis. The prognosis assessment is critical for a correct heart failure management. It has already been demonstrated that a single parameter is weaker for prognosis than different parameters combined. The Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score has been built and validated for heart failure with reduced ejection fraction (HFrEF) patients by considering cardiopulmonary exercise test data combined with clinical, laboratory and echocardiographic measurements. The betablockers treatment is a milestone in the HFrEF management. In the MECKI score database, the association of betablockers treatment with outcome has been investigated in different settings.

BACKGROUND: Upfront combination therapy with ambrisentan and tadalafil has been reported to improve the condition of patients with pulmonary arterial hypertension (PAH) more than with either drug alone. However, little is known about the long-term associated changes in hemodynamics and risk assessment scores. METHODS: This was a multicenter, retrospective analysis of clinical data in 106 patients with newly diagnosed PAH. Clinical evaluations, including demographics, medical history, World Health Organization (WHO) functional class (FC) and 6-minute walk distance (6MWD), right heart catheterization, and Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) risk score 2.0, were assessed over 48 months of ambrisentan‒tadalafil therapy. RESULTS: At baseline, 9 patients (9%) showed a low (8) REVEAL risk score. At a median follow-up of 2 years, 45 patients (43%) showed a low, 47 patients (44%) showed an intermediate, and 14 patients (13%) showed a high REVEAL score, along with improvements in WHO FC, 6MWD and a decrease in mean pulmonary artery pressure and N-terminal pro brain natriuretic peptide (all p < 0.001). Pulmonary vascular resistance (PVR) decreased by 37% from 11.5 ± 6.5 to 7.2 ± 4.1 Wood units (p < 0.001). A total of 61 patients (57%) remained in intermediate-risk or high-risk categories. Low-risk patients had either a decrease in PVR of >50% or a stroke volume within the limits of normal. CONCLUSIONS: Initial combination therapy with ambrisentan and tadalafil in PAH improves the REVEAL risk score in proportion to decreased PVR and preserved stroke volume but still insufficiently so in approximately 50% of the patients.

Background The prognostic role of diabetes mellitus (DM) in heart failure (HF) patients is undefined, since DM is outweighed by several DM-related variables when confounders are considered. We determined the prognostic role of DM, treatment, and glycemic control in a real-life HF population. Methods 3927 HF patients included in the Metabolic Exercise Cardiac Kidney Index (MECKI) score database were evaluated with a median follow-up of 3.66 years (IQR 1.70–6.67). Data analysis considered survival between DM (n = 897) vs. non-DM (n = 3030) patients, and, in diabetics, between insulin (n = 304), oral antidiabetics (n = 479), and dietary only (n = 88) treatments. The role of glycemic control was evaluated grouping DM patients according to glycated hemoglobin (HbA1c): 8% (n = 149). All analyses were performed also adjusting for ejection fraction, renal function, hemoglobin, sodium, exercise peak oxygen uptake, and ventilation/carbon dioxide relationship slope. Study primary endpoint was the composite of cardiovascular death, urgent heart transplantation, or left ventricular assist device implantation. Secondary endpoints were cardiovascular and all causes death. Results For all endpoints, upon adjustment for confounders, DM status and insulin treatment or dietary regimen were not significantly associated with adverse long-term prognosis compared to non-DM and oral antidiabetic treated patients, respectively. A worse prognosis was observed in HbA1c >8% patients (Log-Rank p Conclusion In HF patients, DM, insulin treatment and dietary regimen are not adverse outcome predictors. The only condition related to long-term prognosis, considering potential confounders, is poor glycemic control.

Sacubitril/valsartan improves outcome in patients with heart failure (HF) with reduced left ventricular (LV) ejection fraction (EF, HFrEF). However, little is known about possible mechanisms underlying this favourable effect.To assess changes in echocardiographically-derived hemodynamic profiles induced by sacubitril/valsartan and their impact on outcome.In this multicenter, open-label study, 727 HFrEF outpatients underwent comprehensive echocardiography at baseline (before starting sacubitril/valsartan) and after 12 months. Estimated LV filling pressure (E/e') and cardiac index (CI, l/min/mAt baseline, 29% had profile-A, 15% had profile-B, 32% profile-C, and 24% profile-D. After 12 months, the hemodynamic profile improved in 53% of patients (all profile-A achievers, or profile-D patients achieving either C or B profile), while it remained unchanged in 39% patients and worsened in 9%. Prevalence of improved profile progressively increased with increasing dose of sacubitril/valsartan (P 0.0001). After the second echocardiography, patients were followed up 12.6 ± 7.6 months: event-rate was lower in patients with improved profile (12.3%, 95%CI: 9.4-16.1) compared to patients in whom hemodynamic profile remained unchanged (29.9%, 24.0-37.3) or worsened (31.2%, 20.7-46.9, P 0.0001). Improved hemodynamic profile was associated with favourable outcome independent of LVEF and other covariates (HR 0.65, 95%CI: 0.45-0.95, P 0.05).In HFrEF patients, the beneficial prognostic effects of sacubitril/valsartan are associated with improvement in hemodynamic conditions.

Cardiopulmonary exercise testing is a prognostic tool in heart failure with reduced left ventricular ejection fraction (HFrEF). Prognosticating algorithms have been proposed, but none has been validated. In 2017, a predictive algorithm, based on peak oxygen consumption (VO2), ventilatory response to exercise (ventilation [VE] carbon dioxide production [VCO2], the VE/VCO2 slope), exertional oscillatory ventilation (EOV), and peak respiratory exchange ratio, was recommended, according treatment with β blockers: patients with HFrEF registered in the metabolic exercise test data combined with cardiac and kidney indexes (MECKIs) database were used to validated this algorithm. According to the inclusion/exclusion criteria, 4,683 MECKI patients with HFrEF were enrolled. At 3years follow-up, the end point was cardiovascular death and urgent heart transplantation (cardiovascular events [CV]). CV events occurred in 25% in patients without β blockers, whereas those with β-blockers had 11% (p 10

The angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan (Sac/Val) demonstrated to be superior to enalapril in reducing hospitalizations, cardiovascular and all-cause mortality in patients with ambulatory heart failure and reduced ejection fraction (HFrEF), in particular when it is maximally up-titrated. Unfortunately, the target dose is achieved in less than 50% of HFrEF patients, thus undermining the beneficial effects on the outcomes. In this study, we aimed to evaluate the role of Sac/Val and its titration dose on reverse cardiac remodelling and determine which echocardiographic index best predicts the up-titration success.From January 2020 to June 2021, we retrospectively identified 95 patients (65.6 [59.1-72.8] years; 15.8% females) with chronic HFrEF who were prescribed Sac/Val from the HF Clinics of 5 Italian University Hospitals and evaluated the tolerability of Sac/Val high dose (the ability of the patient to achieve and stably tolerate the maximum dose) as the primary endpoint in the cohort. We used a multivariable logistic regression analysis, with a stepwise backward selection method, to determine the independent predictors of Sac/Val maximum dose tolerability, using, as candidate predictors, only variables with a P-value0.1 in the univariate analyses. Candidate predictors identified for the multivariable backward logistic regression analysis were age, sex, body mass index (BMI), chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), dyslipidaemia, atrial fibrillation, systolic blood pressure (SBP), baseline tolerability of ACEi/ARBs maximum dose, left ventricle global longitudinal strain (LVgLS), LV ejection fraction (EF), tricuspid annulus plane systolic excursion (TAPSE), right ventricle (RV) fractional area change (FAC), RV global and free wall longitudinal strain (RVgLS and RV-FW-LS). After the multivariable analysis, only one categorical (ACEi/ARBs maximum dose at baseline) and three continuous (younger age, higher SBP, and higher TAPSE), resulted significantly associated with the study outcome variable with a strong discriminatory capacity (area under the curve 0.874, 95% confidence interval (CI) (0.794-0.954) to predict maximum Sac/Val dose tolerability.Our study is the first to analyse the potential role of echocardiography and, in particular, of RV dysfunction, measured by TAPSE, in predicting Sac/Val maximum dose tolerability. Therefore, patients with RV dysfunction (baseline TAPSE16 mm, in our cohort) might benefit from a different strategy to titrate Sac/Val, such as starting from the lowest dose and/or waiting for a more extended period of observation before attempting with the higher doses.

BACKGROUND Right heart catheterization (RHC) is recommended by guidelines for the diagnosis of pulmonary hypertension, the definition of hemodynamic impairment and responsiveness to drug therapy. However, RHC is an invasive test with associated risk of complications. Noninvasive echocardiographic tools, possibly predictive of pulmonary hypertension at RHC, could be therefore extremely useful. METHODS Sixty-four consecutive patients with suspected pulmonary hypertension were enrolled in the study and assessed by echocardiography and RHC. Diagnosis of pulmonary hypertension was based on mean pulmonary artery pressure (≥25 mmHg) at RHC. RESULTS Of 64 consecutive patients enrolled, 77% were diagnosed as having pulmonary hypertension after RHC. On the basis of significant differences between patients with pulmonary hypertension at RHC and those without on echocardiographic assessment, a multiple logistic regression model was constructed to predict the presence of pulmonary hypertension at RHC. The score was calculated using right atrium and ventricular diastolic area, tricuspid regurgitation Vmax, tricuspid regurgitation severity degree and left ventricular ejection fraction. The score area under the curve was therefore 0.786 (P = 0.0001), higher than for tricuspid regurgitation Vmax (P = 0.06). A score value more than 57 was associated with a 93% sensitivity, a 67% specificity, a 91% positive predictive power, a 73% negative predictive power, and an odds ratio 27 (P

Aims We assessed the efficacy of add-on drugs in patients with heart failure with reduced ejection fraction (HFrEF) and concomitant chronic kidney disease (CKD) already receiving neurohormonal inhibition (NEUi). Methods and results The literature was systematically searched for phase 3 randomized controlled trials (RCTs) involving ≥90% patients with left ventricular ejection fraction Conclusions Expanding pharmacotherapy beyond NEUi improves outcomes in HFrEF with CKD. 633 Figure

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.

Aim Acute coronary syndromes (ACS) represent one of the major causes of mortality in our country. Lung ultrasound is an important diagnostic tool in the assessment of lung and pleural diseases; it is easy to perform and provides low-cost analysis and it is also easily learned with a few hours of training. To evaluate the usefulness of lung ultrasound in the early diagnosis of pulmonary congestion in patients admitted to ICU for ACS and to evaluate its possible prognostic role in the short and long term. Methods Forty-three patients with ACS admitted in the ICU of Foggia were enrolled in the study between April 2020 and July 2020 (mean age 64.7 ± 12.7 years, male: 67.4%). Medical history, physical examination, ECG, blood analysis, chest X-ray, lung ultrasound and echocardiography were collected at the admission in ICU, after 24 h and at the dismission. All patients were re-evaluated, through a telephone follow-up 3 months after discharge. The primary endpoints were re-hospitalization at 30 days and the following MACEs: development of acute pulmonary oedema during hospitalization, cardiogenic shock, death and the need for oxygen therapy or the use of non-invasive ventilation. The secondary endpoints were out-of-hospital death from cardiac causes and re-hospitalization after 3 months. Results The analysis of the ROC curves showed that pulmonary ultrasound performed on admission in the ICU predicted more than the thoracic physical examination [AUC 0.536 (0.367–0.699); P = 0.111], chest radiograph (AUC 0.561 (0.391–0.721); P = 0.109] and LVEF [AUC 0.525 (0.357–0.689); P = 0.119], the risk of adverse cardiovascular events hospital, although not reaching the cut-off for statistical significance [AUC 0.661 (0.489–0.806); P = 0.0895]. Among all in-hospital events, pulmonary ultrasound predicted higher sensitivity and specificity [AUC 0.665 (0.493–0.809); P = 0.0927] than chest radiography [AUC 0.588 (0.417–0.745); P = 0.113], clinical examination [AUC 0.550 (0.380–0.711); P = 0.116] and LVEF [AUC 0.515 (0.348–0.680); P = 0.125], the use of oxygen therapy and NIV during hospitalization stay. Conclusions In patients with ACS, on admission lung ultrasound predicts the risk of in-hospital events, particularly the use of oxygen therapy or non-invasive mechanical ventilation more than physical examination, chest X-ray and LVEF estimated by echocardiography. It can be considered a complementary method to echocardiography in the evaluation of cardiac function, allowing to estimate the amount of extra-vascular lung water.

Aims Left atrial (LA) enlargement has been demonstrated to be a predictor of adverse cardiovascular outcomes, such as atrial fibrillation (AF), heart failure (HF), and cardiovascular death. Previous studies showed left ventricle ejection fraction (LVEF) improvement and reverse remodelling can be achieved after therapy with sacubitril/valsartan in real-world settings. We sought to investigate the association between left atrial (LA) structural and functional remodelling in patients with chronic HF after therapy with sacubitril/valsartan. Methods and results Patients affected by chronic HF with LV dysfunction (LVEF Conclusions Treatment with sacubitril/valsartan in patients with HFrEF is associated with an improvement in LA functional remodelling in a real-world scenario.

Aims Diabetes is the most common comorbidity of HF patients. SGLT2 inhibitors has been shown to reduce hospitalization in patients with HF. The cardioprotective mechanisms of gliflozines have not been elucidated. The aim of our study was to evaluate the effect of SGLT2 inhibitors on right and left ventricular function in T2DM patients with HF. Methods and results One hundred and fifteen consecutive outpatients with CHF and T2DM were screened in the Daunia Heart Failure Registry. Seventy-eight of them were enrolled and followed up between May 2019 and September 2020. All patients underwent conventional, TDI and strain echocardiography in an ambulatory setting, at the beginning and after 3 months of therapy with SGLT2 inhibitors. Seventy-eight consecutive outpatients with CHF and T2DM (mean age 67.4 ± 8.4 years, male: 83%) were enrolled in the study. Thirty-eight of them started the treatment with SGLT2 inhibitors, while the remaining forty continued their original therapy. After 3 months of therapy, LVEF, LVEDD, and LVESD statistically improved (respectively, from 39.68 ± 7.78% to 45.08 ± 9.04%, P: 0.001 and 57.32 ± 9.76 mm to 54.16 ± 6.54 mm, P: 0.01 and from 47.51 ± 1.58 mm to 43.24 ± 8.12, P: 0.0008). Changes in left ventricular function and dimensions were not significant in patients who did not started a therapy with SGLT2 inhibitors. There was a statistically significant reduction of E/E′ (from 16.51 ± 22.55 to 9.73 ± 3.35, P: 0.0007) in patients with treatment with SGLT2i. Moreover, there was an improvement of right ventricular function, due to a statistically significant reduction of PAPs and increase of TAPSE (respectively, from 30.63 ± 8.80 to 24.00 ± 8.35, P: 0.008; from 19.16 ± 2.54 to 21.18 ± 2.84, P: 0.0003) and S′ (10.42 ± 2.09 to 12.91 ± 2.50, P: 0.000) 3 months after the administration of SGLT2 inhibitors therapy vs. the control group. Conclusions In a real-world scenario, our results showed that the treatment with SGLT-2 inhibitors in patients with CHF and diabetes is associated with an echocardiographic biventricular function improvement.

Aims Pulmonary hypertension (PH) is defined as a mean pulmonary arterial pressure (mPAP) of 25 mmHg or greater at rest, confirmed by right heart catheterization (RHC). The World Health Organization has classified PH into five clinical subgroups. Pulmonary arterial hypertension (PAH) (group 1) is characterized by loss and obstructive remodelling of the pulmonary vascular bed. These patients are characterized haemodynamically by the presence of precapillary PH, defined as an mPAP of 25 mm Hg or greater, pulmonary artery wedge pressure (PAWP) of 15 mm Hg or less, and pulmonary vascular resistance (PVR) of three Wood units (WU) or greater. Pulmonary hypertension due to left-sided heart disease (LHD) (PH-LHD) (group 2) occurs in HF. Patients with PH-LHD usually have isolated postcapillary PH (PAWP >15 mm Hg and PVR 15 mm Hg and PVR ≥3 WU). PH due to chronic lung disease (CLD) (PH-CLD) and/or hypoxia (group 3) can occur in many lung diseases. These patients have precapillary PH. Chronic thromboembolic PH (CTEPH) (group 4) is characterized by obstruction of the pulmonary vasculature by organized thromboembolic material and vascular remodelling, resulting from prior pulmonary embolism. Patients with unclear and/or multifactorial mechanisms are listed as group 5. Specific pulmonary vasodilators are approved only in PAH patients. While research was predominantly focused on pulmonary vasculature, little is known about the peripheral endothelial damage in different vascular beds in PH patients. To evaluate the relationship between the peripheral endothelial function and the haemodynamic parameters, in order to provide a non-invasive method for the indirect evaluation of mean pulmonary pressure and vascular resistance, to predict if the PH is a precapillary or postcapillary, to select more accurately the patients who should undergo RHC. Moreover, we investigate if there is a possible correlation between endothelial dysfunction and response to specific PH therapies. Methods and results Patients with suspected PH, based on symptoms, medical history, and clinics will undergo physical examination, ECG, echocardiography, and RHC. In all patients, endothelial function was assessed by FMD. Medical history, heart rate, systolic blood pressure, body mass index, WHO functional class, and medications were recorded. All patients underwent blood analysis, erythrocyte sedimentation rate (ERS), high sensitivity C-reactive protein (CRP), and NT-proBNP levels were assayed. Increased peripheral endothelial dysfunction in patients with precapillary PH, with a linear correlation between endothelium dysfunction and increased PVR at the right catheterization. To differentiate pre and post capillary PH forms by cut-off values of the FMD. The degree of endothelial dysfunction could be a marker of therapy response. Sequential combination therapy in the pre-capillary PH forms could be the one with a worst endothelial response than up-front combination therapy.

Aims Sacubitril/valsartan have changed the treatment of heart failure with reduced ejection fraction (HFrEF), due to the positive effects morbidity and mortality partly mediated by left ventricular reverse remodelling (LVRR). The aim of this multicentre study was to identify echocardiographic predictors of LVRR after sacubitril/valsartan administration. Methods and results Patients with HFrEF requiring therapy with sacubitril/valsartan from 13 Italian centres were included. Echocardiographic indexes including speckle tracking echocardiography (STE) indexes were used to predict LVRR [defined as LV end-systolic volume reduction and ejection fraction (LVEF) improvement > 10% at follow-up] at 6 months follow-up as the primary endpoint. Changes in symptoms (NYHA class) and neurohormonal activations [N-terminal-pro-brain natriuretic peptide (NTproBNP)] were also evaluated as secondary endpoints. The final population (excluding patients with poor acoustic windows and missing data) consists of 341 patients [mean age: 65 ± 10 years; 18% female, median LVEF 30% (interquartile range: 25–34)]. At 6 months follow-up, 82 (24%) patients showed early complete response (LVRR and LVEF ≥35%), 55 (16%) early incomplete response (LVRR and LVEF Conclusions STE parameters at baseline could be useful to predict LVRR and clinical response to sacubitril-valsartan, and thus could be used as a guide for treatment in patients with HFrEF.

Aims This sub-study deriving from a multicentre Italian register (DISCOVER-ARNI) investigated whether sacubitril/valsartan in adjunction of optimal medical therapy (OMT) could reduce the rate of implantable cardioverter-defibrillator(ICD) indications for primary prevention in heart failure with reduced ejection fraction (HFrEF) according to European guidelines indications, and its potential predictors. Methods and results In this observational study, consecutive patients with HFrEF eligible for sacubitril/valsartan from 13 Italian centres were included. Lack of follow-up or speckle tracking data represented exclusion criteria. Demographic, clinical, biochemical and echocardiographic data were collected at baseline and after 6 months of therapy. Of 351 patients, 225 (64%) were ICD carriers and 126 (36%) were not ICD carriers (of whom 13 had not indication) at baseline. After 6 months of sacubitril/valsartan, among 113 non-ICD carriers despite having baseline left ventricular (LV)EF ≤ 35% and New York Heart Association (NYHA) class = II–III, 69(60%) did not show ICD indications; 44(40%) still fulfilled ICD criteria (Figure 1). Age, atrial fibrillation, mitral regurgitation>moderate, left atrial volume index (LAVi), and LV global longitudinal strain (GLS) significantly varied between the groups. With ROC curves, age ≥ 75 years, LAVi ≥ 42 ml/m2 and LV GLS ≥ −8.3% were associated with ICD indications persistence (AUC = 0.65, 0.68, and 0.68, respectively). With univariate and multivariate analysis, age and LV GLS emerged as the only significant predictors of ICD indications at follow-up. Conclusions Sacubitril/valsartan provided early improvement of NYHA class and LVEF, reducing the possible number of implanted ICD for primary prevention in HFrEF. Baseline advanced age and reduced LV GLS were markers of ICD indication despite OMT. Early therapy with sacubitril/valsartan may save infective/haemorrhagic risks and unnecessary costs deriving from ICDs.

Aims Observational studies have demonstrated that treatment with sacubitril/valsartan may improve left ventricular (LV) systolic and diastolic function in subjects with reduced LV ejection fraction (LVEF) in real-world studies. Subjects with heart failure and reduced EF (HFrEF), however, are also characterized by an impaired right ventricular (RV) function. We therefore aimed to evaluate whether also RV function may improve after S/V therapy and possible predictors of RV improvement could be identified at echocardiography and tissue Doppler imaging. Methods Fifty consecutive patients (67 ± 8 years, LVEF 28 ± 6%, male 86%) with chronic HFrEF and NYHA Classes II–III were followed up for 6 months after therapy with S/V. LV&RV function was assessed at baseline and after 6 months of therapy. Results After 6-month therapy with S/V a significant improvement was shown in the following echocardiography parameters assessing RV function: PAsP (31 ± 11 vs. 35 ± 10 mmHg, P Conclusions In a real-world scenario, 6-month therapy with S/V was associated with an improved RV function in HFrEF. RV function improvement may be predicted by assessing baseline RV S’ and right atrial volume values.

Background Sacubitril/valsartan changed the treatment of heart failure with reduced ejection fraction (HFrEF), due to the positive effects morbidity and mortality partly mediated by left ventricular reverse remodeling (LVRR). The aim of this multicenter study was to identify echocardiographic predictors of LVRR after sacubitril/valsartan administration. Methods Patients with HFrEF requiring therapy with sacubitril/valsartan from 13 Italian centers were included. Echocardiographic indexes including speckle tracking echocardiography (STE) were used to predict LVRR (defined as LV end-systolic volume reduction and ejection fraction [LVEF] improvement >10% at follow-up) at 6 months follow-up as the primary endpoint. Changes in symptoms (NYHA class) and neurohormonal activations (N-terminal-pro-brain natriuretic peptide [NTproBNP]) were also evaluated as secondary endpoints. Patients with poor acoustic windows and missing data were excluded. Results The final population consisted of 341 patients (mean age: 65±10 years; 18% female, median LVEF 30% [interquartile range:25; 34]. At 6 months follow-up, cardiac dimensions and function, including left heart STE parameters, improved (Table 1). Moreover, 82 (24%) patients showed early complete response (LVRR and LVEF ≥35%), 55 (16%) early incomplete response (LVRR and LVEF −9.3% showed a good accuracy in predicting LV RR (Figure 1). LA strain was the best predictor of positive changes in NYHA class and NT-proBNP (all p Conclusions STE parameters at baseline could be useful to predict LVRR and early clinical response to sacubitril-valsartan, and thus could be used as a guide for treatment in patients with HFrEF. Funding Acknowledgement Type of funding sources: None. Table 1Figure 1

COVID-19 pandemic has negatively impacted the management of patients with acute and chronic cardiovascular disease: acute coronary syndrome patients were often not timely reperfused, heart failure patients not adequately followed up and titrated, atrial arrhythmias not efficaciously treated and became chronic. New phenotypes of cardiovascular patients were more and more frequent during COVID-19 pandemic and are expected to be even more frequent in the next future in the new world shaped by the pandemic. We therefore aimed to briefly summarize the main changes in the phenotype of cardiovascular patients in the COVID-19 era, focusing on new clinical challenges and possible therapeutic options.

Aims: Exercise oscillatory ventilation (EOV) is a pivotal cardiopulmonary exercise test parameter for the prognostic evaluation of patients with chronic heart failure (HF). It has been described in patients with HF with reduced ejection fraction (50%, HFpEF), but no data are available for patients with HF with mid-range ejection fraction (40–49%, HFmrEF). The aim of the study was to evaluate the prognostic role of EOV in HFmrEF patients. Methods and results: We analysed 1239 patients with HFmrEF and 4482 patients with HFrEF, enrolled in the MECKI score database, with a 2-year follow-up. The study endpoint was the composite of cardiovascular death, urgent heart transplant, and ventricular assist device implantation. We identified EOV in 968 cases (16% and 17% of cases in HFmrEF and HFrEF,. respectively). HFrEF EOV+ patients were significantly older, and their parameters suggested a more severe HF than HFrEF EOV− patients. A similar behaviour was found in HFmrEF EOV+ vs. EOV− patients. Kaplan–Meier analysis, irrespective of ejection fraction, showed that EOV is associated with a worse survival, and that patients with HFrEF and HFmrEF EOV+ had a significantly worse outcome than the EOV− of the same ejection fraction groups. EOV-associated survival differences in HFmrEF patients started after 18 months of follow-up. Conclusion: Exercise oscillatory ventilation has a similar prevalence and ominous prognostic value in both HFmrEF and HFrEF patients, indicating a group of patients in need of a more intensive follow-up and a more aggressive therapy. In HFmrEF, the survival curves between EOV+ and EOV− patients diverged only after 18 months.

Despite relative frequency of delirium in elderly hospitalized heart failure patients, skills and expertise in managing such complication are usually poor for physicians and nurses facing this clinical condition. International guidelines on heart failure do not provide detailed indication for such clinical condition, and evidence on this topic is limited. A multi-disciplinary approach (cardiologists, internists, geriatricians, psychologists, and psychiatrists) is often required; this review will therefore focus on diagnosis and clinical management of delirium in heart failure patients from a multidisciplinary point of view.

Patients with advanced heart failure have poor prognosis despite traditional pharmacological therapies. The early identification of these subjects would allow them to be addressed on time in dedicated centers to select patients eligible for heart transplantation or ventricular assistance. In this article we will report the current management of these patients based on latest international guidelines, underlining some critical aspects, with reference to future perspectives.

Takotsubo syndrome (TTS) can be induced by a large variety of physical/emotional triggers; several cases, however, are related to either an overt or occult malignancy, as shown in retrospective studies and case reports. The aim of this study was therefore to evaluate the clinical outcome of patients with TTS and cancer in a meta-analysis study. In June 2018, a Pubmed systematic research was conducted for studies assessing outcome in patients with TTS and cancer. We assessed Mantel-Haenszel pooled estimates of risk ratios (RRs) and 95% confidence intervals (CIs) for adverse events at follow-up. After paper retrieval, four studies were included in the meta-analysis, with a total of 123,563 patients. The prevalence of current or previous malignancy among patients admitted with TTS was 6.7% (8258 patients). When compared to control patients, patients with cancer showed an increased risk of clinical events (RR 3.24, 95% CI 3.04–3.45, p

Aims: Exercise-derived parameters, specifically peak exercise oxygen uptake (peak VO2) and minute ventilation/carbon dioxide relationship slope (VE/VCO2 slope), have a pivotal prognostic value in heart failure (HF). It is unknown how the prognostic threshold of peak VO2 and VE/VCO2 slope has changed over the last 20 years in parallel with HF prognosis improvement. Methods and results: Data from 6083 HF patients (81% male, age 61 ± 13 years), enrolled in the MECKI score database between 1993 and 2015, were retrospectively analysed. By enrolment year, four groups were generated: group 1 1993–2000 (n = 440), group 2 2001–2005 (n = 1288), group 3 2006–2010 (n = 2368), and group 4 2011–2015 (n = 1987). We compared the 10-year survival of groups and analysed how the overall risk (cardiovascular death, urgent heart transplantation, or left ventricular assist device implantation) changed over time according to peak VO2 and VE/VCO2 slope and to major clinical and therapeutic variables. At 10 years, a progressively higher survival from group 1 to group 3 was observed, with no further improvement afterwards. A 20% risk for peak VO2 15 mL/min/kg (95% confidence interval 16–13), 9 (11–8), 4 (4–2) and 5 (7–4) was observed in group 1, 2, 3, and 4, respectively, while the VE/VCO2 slope value for a 20% risk was 32 (37–29), 47 (51–43), 59 (64–55), and 57 (63–52), respectively. Conclusions: Heart failure prognosis improved over time up to 2010 in a HF population followed by experienced centres. The peak VO2 and VE/VCO2 slope cut-offs identifying a definite risk progressively decreased and increased over time, respectively. The prognostic threshold of peak VO2 and VE/VCO2 slope must be updated whenever HF prognosis improves.

The usefulness of β-blockers in heart failure (HF) patients with permanent atrial fibrillation (AF) has been questioned. Background: The usefulness of β-blockers in heart failure (HF) patients with permanent atrial fibrillation (AF) has been questioned. Methods and results: We analyzed data from HF patients (958 patients (801 males, 84%, age 67 ± 11 years)) with AF enrolled in the MECKI score database. We evaluated prognosis (composite of cardiovascular death, urgent heart transplant, or left ventricular assist device) of patients receiving β-blockers (n = 777, 81%) vs. those not treated with β-blockers (n = 181, 19%). We also analyzed the role β1-selectivity and the role of daily β-blocker dose. To account for different HF severity, Kaplan-Meier survival curves were normalized for relevant confounding factors and for treatment strategies. Dose was available in 629 patients. Median follow-up was 1312 (577–2304) days in the entire population, 1203 (614–2420) and 1325 (569–2300) days in patients not receiving and receiving β-blockers. 224 (23%, 54/1000 events/year), 163 (21%, 79/1000 events/year), and 61 (34%, 49/1000 events/year) events were recorded, respectively. At 10-year patients treated with β-blockers had a better outcome (HR 0.447, p < 0.01) with no effects as regards β1selective drugs (53%) vs. β1-β2 blockers (47%). Survival improved in parallel with β-blocker dose increase (HR 0.296, 0.496, 0.490 for the high, medium, and low dose vs. no β-blockers, p < 0.0001). Conclusion: HF patients with AF taking a β-blocker have a better outcome (with a survival improvement in parallel with daily dose but no differences as regards β1 selectivity) but this does not mean that β-blockers improve outcomes in these patients as we cannot control for all the potential confounders associated with β-blocker use.

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.