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Background: Diastolic dysfunction (DD) assessment in heart failure is still challenging. Peak atrial longitudinal strain (PALS) is strongly related to end-diastolic pressure and prognosis, but it is still not part of standard DD assessment. We tested the hypothesis that a machine learning approach would be useful to include PALS in DD classification and refine prognostic stratification. Methods: In a derivation cohort of 864 heart failure patients in sinus rhythm (age, 66.6±12 years; heart failure with reduced ejection fraction, n=541; heart failure with mildly reduced ejection fraction, n=129; heart failure with preserved ejection fraction, n=194), machine learning techniques were retrospectively applied to PALS and guideline-recommended diastolic variables. Outcome (death/heart failure rehospitalization) of the identified DD-clusters was compared with that by guidelines-based classification. To identify the best combination of variables able to classify patients in one of the identified DD-clusters, classification and regression tree analysis was applied (with DD-clusters as dependent variable and PALS plus guidelines-recommended diastolic variables as explanatory variables). The algorithm was subsequently validated in a prospective cohort of 189 heart failure outpatients (age, 65±13 years). Results: Three distinct echocardiographic DD-clusters were identified (cluster-1, n=212; cluster-2, n=376; cluster-3 DD, n=276), with modest agreement with guidelines-recommended classification (kappa=0.40; P P =0.033; net reclassification improvement 0.166 [95% CI, 0.035–0.276], P =0.013), without interaction with ejection fraction category. In the validation cohort (median follow-up: 18.5 months), cluster-based classification better predicted outcome than guideline-based classification (C-index 0.80 versus 0.78, P =0.093). Conclusions: Integrating PALS by machine learning algorithm in DD classification improves risk stratification over recommended current criteria, regardless of ejection fraction status. This proof of concept study needs further validation of the proposed algorithm to assess generalizability to other populations.

International audience; Aims Pulmonary congestion during exercise assessed by lung ultrasound predicts negative outcome in patients with heart failure with preserved ejection fraction (HFpEF). We aimed at assessing predictors of exercise-induced pulmonary B-lines in HFpEF patients. Methods and results Eighty-one I-II NYHA class HFpEF patients (65.0 ± 8.2 y/o, 56.8% females) underwent standard and strain echocardiography, lung ultrasound, and natriuretic peptide assessment during supine exercise echocardiography (baseline and peak exercise). Peak values and their changes were compared in subgroups according to exercise lung congestion grading (peak B-lines >10 or ≤10). Exercise elicited significant changes for all echocardiographic parameters in both subgroups [39/81 (48.1%) with peak B-lines >10; 42/81 (51.9%) with B-lines ≤10]. Peak values and changes of E-wave (and its derived indices) were significantly higher in patients with >10 peak B-lines compared with those with ≤10 B-line (all P-values 10 (all P-values

Introduction Left atrial appendage (LAA) is a finger-like muscular extension of the left atrium (LA). It acts as blood reservoir, modulates LA pressure and elicits adaptive responses to stress. Several LAA shapes and variants have been described. We report a case of congenital absence of LAA diagnosed by transesophageal echocardiography (TEE) and confirmed by computed tomography (CT). Case report A 55-year-old male patient with history of hypertension was admitted to our hospital for an episode of atrial fibrillation (AF). TEE was performed and showed normal LA volume, absence of thrombi and spontaneous echo contrast in the LA, but, despite acquiring three-dimensional (3D) en-face views, we were unable to identify LAA. Congenital absence of LAA was suspected and multidetector cardiac CT confirmed the abnormality. Discussion Congenital absence of LAA is an extremely rare condition: only eighteen cases were described on a review of the literature published in 2020. Associations with other congenital abnormalities or with atrial fibrillation have been reported, but a causal relationship cannot be established. Multiple imaging modalities can be used to define the anatomy and function of LAA, to detect or rule out in situ thrombosis and to guide catheter-based therapies, but the most widely used technique is TEE. Among intracardiac thrombi in patients with non-valvular atrial fibrillation, more than 90% are identified in the LAA, meaning that the remaining 10% may develop in other sites of the LA. The congenital absence of LAA could be considered similar to LAA percutaneous occlusion or surgical exclusion; because of the few published randomized controlled trials, the current ESC guidelines on atrial fibrillation are unclear about the true thrombotic risk in these cases. Since LAA percutaneous occlusion is actually indicated only in cases of contraindications for long-term anticoagulant treatment, in our opinion in patients with non-valvular AF, LAA congenital absence, high stroke risk and low bleeding risk, anticoagulant therapy should be considered. Conclusion Congenital absence of LAA is an extremely rare condition and its pathophysiological role, especially with regard to antithrombotic therapy in patients with AF, is still not well defined.

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.

Ejection fraction (EF) is still widely used to categorize heart failure (HF) patients but has limitations. Global longitudinal strain (GLS) has emerged as a new prognosticator in HF, independent of EF.We investigated the incremental predictive benefit of GLS over different risk profiles as identified by automated cluster analysis of simple echocardiographic parameters.In 797 HFrEF patients (age 66 ± 12y; mean EF 30 ± 7%), unsupervised cluster analysis of 10 routine echocardiographic variables (without GLS) was performed. Median follow-up was 37 months. End-point was all-cause mortality. Association between risk profiles, GLS, and mortality was assessed by Cox proportional-hazard modeling with interaction term. Cluster analysis allocated patients to 3 different risk phenogroups (PG): PG-1 (mild diastolic dysfunction [DD], moderate systolic dysfunction, no pulmonary hypertension, normal right ventricular [RV] function); PG-2 (moderate DD, mild pulmonary hypertension, normal RV function); PG-3 (severe DD, advanced systolic dysfunction, pulmonary hypertension, RV dysfunction). Compared to PG-1, PG-2 and PG-3 showed increased adjusted-hazard ratio (1.71; 95% CI:1.05-2.77, P = 0.30; and 2.58; 95% CI:1.50-4.44, P 0.001, respectively). GLS was independently associated with outcome in the whole population (adjusted-HR: 1.11; 95% CI: 1.05-1.17, P = 0.001); however, profile membership modified the relationship between GLS and outcome which was no longer significant in PG-3 (P for interaction = 0.003).Within HFrEF populations, clustering of routine echocardiography parameters can automatically identify patients with different risk profiles; further assessment by GLS may be useful for patients with not advanced disease.

Aims: Heart failure (HF) and atrial fibrillation (AF) may coexist and influence each other. However, characteristics, anticoagulant treatment, and outcomes of contemporary AF patients with concurrent HF are ill-defined. This study analyses characteristics, treatment, and 2year outcomes in newly diagnosed Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) patients with vs. without HF. Methods and results: GARFIELD-AF is the world's largest observational AF patient study. At enrolment, 11758 of 52072 patients (22.6%) had HF; 76.3% were New York Heart Association class II–III. Patients with HF had comparable demographics, blood pressure, and heart rate but more likely had permanent (15.6% vs. 11.9%) or persistent AF (18.9% vs. 13.8%), acute coronary syndromes (16.7% vs. 8.9%), vascular disease (40.8% vs. 20.2%), and moderate-to-severe chronic kidney disease (14.6% vs. 9.0%) than those without. Anticoagulant prescription was similar between the two groups. At 2year follow-up, patients with HF showed a greater risk of all-cause mortality [hazard ratio (HR), 2.06; 95% confidence interval (CI), 1.91–2.21; P&nbsp

SGLT2 inhibitors reduce cardiovascular death or hospitalization for heart failure, regardless of the presence or absence of diabetes in patients at high cardiovascular risk and in those with heart failure and reduced ejection fraction (HFrEF). In patients with HF and preserved EF, empagliflozin also showed favorable effects mainly related to the reduction of hospitalization for heart failure. These favorable effects are beyond the reduction of glycemic levels and mainly related to beneficial hemodynamic and anti-inflammatory effects of these drugs and improved cardiac energy metabolism. In this review, we aimed to evaluate the effects of SGLT2 inhibitor on cardiac remodeling and function, which is still incompletely clear.

Background and aims It is unknown whether the prognostic role of diabetes (T2DM) in outpatients with chronic heart failure (CHF) is independent of the most important echocardiographic markers of poor prognosis. The aims of this analysis were to evaluate whether T2DM modifies the risk of mortality in CHF patients stratified by etiology of disease or by right-ventricular to pulmonary arterial coupling at echocardiography and to evaluate how T2DM interacts with the prognostic role of cardiac plasma biomarkers. Methods and results This is a retrospective analysis of 1627 CHF outpatients who underwent a complete echocardiographic examination. During a median follow-up period of 63 months 255 patients died. Poor right-ventricular to pulmonary arterial coupling and reduced left ventricular ejection fraction were independent predictors of outcome, whereas ischemic etiology and T2DM were not. T2DM interacted with etiology increasing the risk of mortality by 32% among patients with ischemic disease (p = 0.003). Elevated hsTNI plasma levels were associated with poor survival in T2DM but not in non-diabetic patients. Conclusion T2DM signals a worse outcome in ischemic CHF patients regardless of the echocardiographic phenotype. High plasma levels of hsTNI are stronger predictors of mortality in CHF patients with T2DM than in patients without diabetes.

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.

Coronary artery disease is a major underlying etiology for heart failure. The role of coronary microvascular disease, and endothelial dysfunction, in the pathophysiology of heart failure is poorly appreciated. Endothelial dysfunction, induced by oxidative stress, contributes to the development of heart failure. Alterations of endothelial function and nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway are involved in the pathophysiology of heart failure with both reduced and preserved ejection fraction. Indeed, an altered endothelium dependent vasodilatation, causing repeated episodes of ischemia/reperfusion, can induce a chronic stunned myocardium with systolic dysfunction and an increased diastolic stiffness with diastolic dysfunction. Moreover, the altered NO-cGMP pathway directly affects myocardial homeostasis. Endothelial dysfunction is associated with worse prognosis and higher rate of cardiovascular events. Potential therapeutic strategies targeting the NO-cGMP pathway in patients with HF will be discussed in this review article. Although clinical data are still inconclusive, the NO-cGMP pathway represents a promising target for 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.

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

Background Patients with heart failure undergoing cardiac resynchronization therapy with or without defibrillator function may exhibit recovery of left ventricular ejection fraction (LVEF) during follow-up. Mechanical dispersion (MD; the SD of time to peak longitudinal strain by two-dimensional speckle-tracking echocardiography) is a known predictor of life-threatening ventricular arrhythmias (VAs). Relationships among LVEF recovery, changes in MD, and incidence of VA are still not extensively investigated. Methods In this retrospective study, recipients of cardiac resynchronization therapy defibrillation (n = 183) or implantable cardioverter-defibrillators only (n = 87) underwent conventional and speckle-tracking echocardiography, both at baseline and after 10 to 12 months, and were followed clinically. Both a ≥10% increase in LVEF and a final LVEF > 35% defined echocardiographic response (EchoResp). Reduction in MD ≥10 msec defined MD response (MDResp). Risk for appropriate implantable cardioverter-defibrillator therapy for VAs was assessed using a multivariable Cox hazard model. Results The prevalence of EchoResp+ and MDResp+ was 39% and 46%, respectively. During follow-up (49.8 ± 33.5 months), 74 VA events occurred. The incidence rate (per 100 patient-years) of VAs was lowest in the EchoResp+/MDResp+ group (1.66%; 95% CI, 0.69%-3.99%), highest in the EchoResp−/MDResp− group (12.8%; 95% CI, 9.53%-17.2%; P 71.4 msec) was associated with VAs independent of whether final LVEF was below or above the guideline-reported cutoff of 35% (P Conclusions Among ICD recipients, improvements in both left ventricular function and MD are associated with reduced risk for VAs. In patients whose follow-up LVEFs improved to >35%, risk for VAs, although substantially decreased, remained elevated in the presence of still elevated MD.

Idarucizumab (Praxbind) is a humanized antibody fragment, that reversibly and with high affinityties up dabigatran (Pradaxa). Anticoagulation reversal is achieved immediately, and with no procoagulant effect. It is administered intravenously and clearance is renal. The main clinical application of idarucizumab is to antagonize bleeding related to dabigatran, especially if it occurs at critical sites, such as nervous system (central or peripheral), intraocular, pericardial, retroperitoneal or pulmonary. Other indications are: i) dabigatran-induced anticoagulation reversal in the need for emergency surgery or procedures at high risk of bleeding; and ii) second-line treatment in bleedings that persist despite local hemostasis procedures. In this narrative review, we comprehensively address clinical indications for idarucizumab, summing up evidence derived from a systematic literature review, but also from case reports.

Aims: In patients with heart failure with reduced ejection fraction (HFrEF), an association between left atrial (LA) dilatation and dysfunction is expected, but the degree of coexistence of the two abnormalities and their relative prognostic role is not known. Methods and results: A total of 626 HFrEF patients formed the study population. All of them underwent a comprehensive echocardiographic evaluation. LA maximal volume was indexed to body surface area (LAVi); LA function was assessed using strain analysis during the reservoir phase: peak atrial longitudinal strain (PALS) analysis. Study primary endpoint was overall mortality or hospitalization for worsening heart failure. Four groups of patients were included in this study according to LAVi (≤34 or >34 mL/m2 ) and PALS (≤23% or >23%); 61 (10%) patients had normal LA volume and function (Group 1), 58 (9%) had LA dilatation but normal function (Group 2), 100 (16%) had normal volume but abnormal function (Group 3), and 407 (65%) had enlarged left atrium and abnormal function (Group 4). PALS was associated with primary endpoint in patients with both normal-size [Groups 1 and 3: hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.88-0.96; P = 0.0006] and dilated left atria (Groups 2 and 4: HR 0.93, 95% CI 0.91-0.96; P < 0.0001). In contrast, LAVi was associated with the primary endpoint in patients with abnormal LA function (Groups 3 and 4: HR 1.018, 95% CI 1.011-1.024; P < 0.00001) but not in those with normal PALS (Groups 1 and 2: HR 1.023, 95% CI 0.99-1.057; P = 0.1). Conclusions: Left atrial dilatation and dysfunction frequently but not invariably coexist. PALS emerged as a significant prognostic parameter in HFrEF even in the absence of LA dilation.

Several parameters have proven useful in assessing prognosis in outpatients with heart failure with preserved ejection fraction (HFpEF). In contrast, prognostic determinants in HFpEF hospitalized for an acute event are poorly investìgated.To determine the predictive value of NT-proBNP, and diastolic function (assessed by E/e'), in patients with HFpEF hospitalized for acute heart failure.We evaluated 205 consecutive HFpEF patients admitted for acute heart failure (median age: 76[53,81], 36% male, median EF: 61 [54,77]). We assessed clinical, echocardiographic, and NT-proBNP values, on admission and at discharge. Primary end-point was the composite of all-cause death and/or HF rehospitalization. After a mean follow up of 28±10 months, 82 patients met the primary end-point; there were 30 deaths (14.6%), and 72 patients (35%) were rehospitalized for HF. By multivariable analysis, predictors of the composite end-point were: discharge E/e´ ≥14 (HR: 4.63 CI 95%: 2.71-18.2, p0.0001), discharge NT-proBNP ≥1500 pg/ml (HR: 5.23, CI 95%: 2.87-17.8, p 0.0001), ≥50% NT-proBNP decrease between admission and discharge (HR: 0.62, CI 95%: 0.25-0.79, p = 0.019). Combining E/e´ and NT-proBNP values at discharge further and significantly improved discrimination power compared to each variable analyzed separately (AUC, NT-proBNP at discharge: 0.80; E/e´ at discharge: 0.77; E/e´ + NT-proBNP: 0.88; p 0.01).In HFpEF patients hospitalized with acute heart failure, assessment of E/e´ ratio and NT-proBNP at discharge provides prognostic information on top of other variables, and allows to easily identify a population at higher risk of subsequent death or rehospitalization for heart failure, during a medium-term follow up.

Background: Patients with heart failure (HF) with preserved ejection fraction (HFpEF) typically develop dyspnea and pulmonary congestion upon exercise. Lung ultrasound is a simple diagnostic tool, providing semiquantitative assessment of extravascular lung water through B-lines. It has been shown that patients with HFpEF develop B-lines upon submaximal exercise stress echocardiography; however, whether exercise-induced pulmonary congestion carries prognostic implications is unknown. This study aimed at evaluating the prognostic value of B-line assessment during exercise in patients with HFpEF. Methods: Sixty-one New York Heart Association class I to II patients with HFpEF underwent standard echocardiography, lung ultrasound (28-scanning point method), and BNP (B-type natriuretic peptide) assessment during supine exercise echocardiography (baseline and peak exercise). The primary end point was a composite of cardiovascular death or HF hospitalization at 1 year. Results: B-lines, E/e′, and BNP significantly increased during exercise ( P P P =0.002) B-lines were retained as independent predictors of outcome (hazard ratios per 1 B-line increment), along with BNP and E/e′ ratio. Importantly, adding peak B-line on top of a clinical model significantly improved prognostic accuracy (C-index increase, 0.157 [0.056–0.258], P =0.002) and net reclassification (continuous net reclassification improvement, 0.51 [0.09–0.74], P =0.016), with similar results for B-line change. Conclusions: Detection of exercise-induced pulmonary congestion by lung ultrasound is an independent predictor of outcome in patients with HFpEF; its use may help refining the routine risk stratification of these patients on top of well-established clinical variables.

Aims To evaluate whether the clinical and echocardiographic correlates and the prognostic significance of right ventricular (RV) dysfunction are different in heart failure patients with reduced (HFrEF), mid-range (HFmrEF), or preserved (HFpEF) left ventricular ejection fraction. Methods and results The study included 1663 patients with heart failure caused by ischaemic or hypertensive heart disease or by idiopathic cardiomyopathy. Left ventricular ejection fraction was 40 mmHg was by far the strongest correlate of a reduced TAPSE in HFpEF and HFmrEF patients (interaction analysis, P = 0.0011). TAPSE/PASP proved to be a powerful predictor of prognosis in all patients. Conclusions The correlates of RV dysfunction differ in HFrEF compared with HFpEF and HFmrEF patients. Regardless of the extent of LV dysfunction, the TAPSE/PASP ratio is a powerful independent predictor of prognosis in all heart failure patients.

Background Left atrial (LA) volume is a marker of cardiac remodeling and prognosis in heart failure (HF) with reduced ejection fraction (EF), but LA function is rarely measured or characterized. We investigated determinants and prognostic impact of LA reservoir function in patients with HF with reduced EF. Methods and Results In 405 patients with stable HF with reduced EF (EF, ≤40%) in sinus rhythm, we assessed LA reservoir function by both LA total EF (by phasic volume changes) and peak atrial longitudinal strain (PALS; by speckle tracking echocardiography); LA functional index was also calculated. During follow-up (median, 30 months; Q1-Q3, 13-52), 139 patients (34%) reached the composite end point (all-cause death/HF hospitalization). Median PALS was 15.5% (interquartile range, 11.2-20.6). By univariable analysis, all LA function parameters significantly predicted outcome ( P0.01 for all), with PALS showing the highest predictive accuracy (area under the curve, 0.75; sensitivity, 73%; specificity, 70%). Impaired PALS was associated with greater left ventricular and LA volumes, worse left ventricular EF, left ventricular global longitudinal strain, right ventricular systolic function, and more severe diastolic dysfunction. After multivariable adjustment (including LA volume and left ventricular global longitudinal strain), PALS, but not LA total EF or LA functional index, remained significantly associated with outcome (hazard ratio per 1-SD decrease, 1.38; 95% CI, 1.05-1.84; P=0.030). Adding PALS to a base model, including age, sex, LA volume, EF, E/E' ratio, and global longitudinal strain, provided incremental predictive value (continuous net reclassification improvement, 0.449; P=0.0009). Conclusions In HF with reduced EF, assessment of LA reservoir function by PALS allows powerful prognostication, independently of LA volume and left ventricular longitudinal contraction.

Background Left atrial (LA) volume is a marker of cardiac remodeling and prognosis in heart failure (HF) with reduced ejection fraction (EF), but LA function is rarely measured or characterized. We investigated determinants and prognostic impact of LA reservoir function in patients with HF with reduced EF. Methods and Results In 405 patients with stable HF with reduced EF (EF, ≤40%) in sinus rhythm, we assessed LA reservoir function by both LA total EF (by phasic volume changes) and peak atrial longitudinal strain (PALS; by speckle tracking echocardiography); LA functional index was also calculated. During follow-up (median, 30 months; Q1–Q3, 13–52), 139 patients (34%) reached the composite end point (all-cause death/HF hospitalization). Median PALS was 15.5% (interquartile range, 11.2–20.6). By univariable analysis, all LA function parameters significantly predicted outcome ( P P =0.030). Adding PALS to a base model, including age, sex, LA volume, EF, E/E′ ratio, and global longitudinal strain, provided incremental predictive value (continuous net reclassification improvement, 0.449; P =0.0009). Conclusions In HF with reduced EF, assessment of LA reservoir function by PALS allows powerful prognostication, independently of LA volume and left ventricular longitudinal contraction.

Global right ventricular (RV) longitudinal strain (RVGLS) and free wall RV longitudinal strain (RVFWS) have both been advocated as sensitive tools to evaluate RV function and predict prognosis in patients with heart failure and reduced ejection fraction (HFrEF). However, because the interventricular septum is an integral part of the left ventricle (LV) also, RVGLS might be influenced by LV dysfunction. Thus, we compared the prognostic performance of either RV strain parameter in HFrEF patients, also taking into account the degree of LV systolic dysfunction.In 288 prospectively enrolled outpatients with stable HFrEF, RVGLS and RVFWS were assessed by speckle-tracking and LV systolic function by global longitudinal strain and LV ejection fraction. Patients were followed up for 30.2 ± 23.0 months; the primary endpoint was all-cause death/heart failure-related hospitalization. Prognostic performance was assessed by C-statistic and net reclassification improvement.There were 95 events during follow-up. By univariable analysis, both RVGLS (hazard ratio × 1 SD, 1.60; 95% CI, 1.29-1.99; P .0001) and RVFWS (hazard ratio × 1 SD, 1.82; 95% CI, 1.45-2.29; P .0001) were associated with outcome, and both remained significant after correction for EMPHASIS risk score, New York Heart Association class, natriuretic peptides, and therapy. However, after further correction for LV systolic function parameters, only RVFWS remained significantly associated with outcome (P .01). A basic prediction model was improved by adding RVFWS (net reclassification improvement 0.390; P .05), but not RVGLS.Although both RVGLS and RVFWS have prognostic value, RVFWS better predicts outcome in HFrEF patients, mainly because it is less influenced by LV longitudinal dysfunction.

AIMS A compromised tricuspid annular plane systolic excursion (TAPSE) is associated with worse survival in patients with chronic heart failure with reduced ejection fraction (HFrEF). However, it is not known whether a reversible abnormal TAPSE at follow-up predicts survival. Our aim was to evaluate whether a reversible abnormal TAPSE is associated with a better survival in patients with chronic HFrEF. METHODS AND RESULTS A complete echocardiography was performed in 706 patients with chronic HFrEF (LVEF ≤45%) at baseline and after 6 ± 3 months. Right ventricular (RV) systolic function was evaluated using TAPSE. The study endpoint was all-cause mortality. At baseline, TAPSE was severely reduced (≤14 mm) in 89 (13%) patients, and slightly reduced (>14 but

We compared the follow-up data on loop diuretic use and renal function, as assessed by serum creatinine levels, and the estimated glomerular filtration rate (eGFR), of two groups of consecutive ambulatory HF patients: 1) the clinically-guided group, in which management was clinically driven based on the institutional protocol of the HF Unit of the Cardiovascular and Thoracic Department of Pisa (standard of care) and 2) the echo and B-type natriuretic peptide (BNP) guided group (patients conforming to the protocol of the Network Labs Ultrasound (NEBULA) in HF Study Group: Pisa, Perugia, Pavia; Verona, Auckland, and Veruno), in which therapy was delivered according to the serial assessment of BNP and echocardiography. Patients whose follow-up was based on standard of care had a significant higher prevalence of worsening renal function, that was likely related to higher diuretic dosages, whilst, a better management of renal function was observed in the echo-BNP-guided group. The data is related to “Echo and natriuretic peptide guided therapy improves outcome and reduces worsening renal function in systolic heart failure: An observational study of 1137 outpatients” (A. Simioniuc, E. Carluccio, S. Ghio, A. Rossi, P. Biagioli, G. Reboldi, G.G. Galeotti, F. Lu, C. Zara, G. Whalley, P.G. Temporelli, F.L. Dini, 2016; K.J. Harjai, H.K. Dinshaw, E. Nunez, M. Shah, H. Thompson, T. Turgut, H.O. Ventura, 1999; A. Ahmed, A. Husain, T.E. Love, G. Gambassi, L.J. Dell׳Italia, G.S. Francis, M. Gheorghiade, R.M. Allman, S. Meleth, R.C. Bourge, 2006) [1–3].

Background and aims Elevated serum uric acid (sUA) concentrations have been associated with worse prognosis in heart failure (HF) but little is known about elderly patients. We aimed to assess long-term additive prognostic value of sUA in elderly patients hospitalized for HF. Methods and results Clinical and echocardiographic characteristics of 310 consecutive elderly patients hospitalized for HF were collected. During index period, 206 had sUA concentrations available, which were obtained within 24 h prior to discharge; 10 patients were lost to follow-up, leaving 196 patients available. Patients had a median age of 77 (IQR 69–83) years, and were mostly male (64.5%). sUA ranges for tertiles I–III were: 1.5–6.1, 6.2–8.3, and 8.4–18.9 mg/dl, respectively. During a median follow-up of 27 months (IQR 10.5–39.5), 122 combined events occurred (87 deaths and 73 HF rehospitalizations). Four-year event-free survival for the combined endpoint was 46 ± 7% for tertile I, 34 ± 7% for tertile II, and 21 ± 5% for tertile III (P = 0.001). By multivariable Cox backward analysis, sUA was retained as a significant predictor. Compared with the lowest sUA tertile, tertile III showed a strong association with outcome, also after adjustment for other predictors (HR 1.84, 95% CI 1.16–2.93; P = 0.01). Importantly, addition of sUA to the other significant predictors of outcome resulted in improved risk classification (net reclassification improvement 0.19, P = 0.017). Conclusions High sUA at discharge is a strong predictor of adverse outcome in elderly hospitalized for HF, and it significantly improves risk classification. Measuring sUA can be a simple and useful tool to identify high-risk elderly hospitalized for HF.

Background: Current diagnosis of heart failure with preserved ejection fraction (HFpEF) is suboptimal. We tested the hypothesis that comprehensive machine learning (ML) of left ventricular function at rest and exercise objectively captures differences between HFpEF and healthy subjects. Methods and Results: One hundred fifty-six subjects aged >60 years (72 HFpEF+33 healthy for the initial analyses; 24 hypertensive+27 breathless for independent evaluation) underwent stress echocardiography, in the MEDIA study (Metabolic Road to Diastolic Heart Failure). Left ventricular long-axis myocardial velocity patterns were analyzed using an unsupervised ML algorithm that orders subjects according to their similarity, allowing exploration of the main trends in velocity patterns. ML identified a continuum from health to disease, including a transition zone associated to an uncertain diagnosis. Clinical validation was performed (1) to characterize the main trends in the patterns for each zone, which corresponded to known characteristics and new features of HFpEF; the ML-diagnostic zones differed for age, body mass index, 6-minute walk distance, B-type natriuretic peptide, and left ventricular mass index ( P Conclusions: The analysis of left ventricular long-axis function on exercise by interpretable ML may improve the diagnosis and understanding of HFpEF.

Aims Residual pulmonary congestion at discharge is associated with poor prognosis in heart failure (HF), but its quantification through physical examination is challenging. Ultrasound imaging of lung comets (B-lines) could improve congestion evaluation. The aim of this study was to assess the short-term prognostic value of B-lines after discharge from HF hospitalisation compared with other indices of haemodynamic congestion (BNP, E/e', and inferior vena cava diameter) or clinical status (NYHA class). Methods and results Sixty consecutive HF inpatients underwent clinical examination, echocardiography, and lung ultrasound at discharge, independently of, and in addition to routine management by the attending physicians. The median B-line count was 8.5 (5–34). Three-month event-free survival for the primary endpoint (all-cause death or HF hospitalisation) was 27 ± 10% in patients with ≥30 B-lines and 88 ± 5% in those with