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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/m2) were combined to determine 4 hemodynamic profiles: profile-A (normal-flow/normal-pressure); profile-B (low-flow/normal-pressure); profile-C: (normal-flow/high-pressure); profile-D: (low-flow/high-pressure). Changes among categories were recorded, and their associations with rates of the composite of death/HF-hospitalization were assessed by multivariable Cox analysis. At 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. • Sacubitril/valsartan (S/V) improves outcome in HFrEF outpatients. • S/V improves non-invasive assessment of cardiac output and LV filling pressure. • Long-term risk of death/HF-hospitalization is reduced after this hemodynamic improvement. • Prognostic benefit of hemodynamic improvement is independent on LVEF improvement. [ABSTRACT FROM AUTHOR]

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. • HFrEF patients are extremely heterogeneous regarding etiology, clinical manifestations, and natural history. • Cluster analysis allows identification of "echocardiographic phenogroups" with considerably different disease severity. • The prognostic role of Global Longitudinal Strain varies across HF disease severity being not significant in advanced stage. [ABSTRACT FROM AUTHOR]

Current guidelines do not recommend periodically repeating echocardiograms in the follow-up of stable heart failure patients with reduced ejection fraction (HFrEF). The objective of the study was to verify the additional prognostic information provided by a comprehensive re-assessment of their cardiac function and hemodynamic profile at Doppler echocardiography in HFrEF patients. Retrospective analysis of 769 stable HFrEF outpatients who underwent two complete echocardiograms, at baseline and at re-assessment. Main candidate predictors of prognosis were: left ventricular (LV) filling pattern, pulmonary artery systolic pressure (PASP) and right ventricular function (TAPSE). Age, LV ejection fraction, mitral regurgitation severity, NYHA class, brain natriuretic peptide plasma levels at baseline, and their changes at 12 months, were used as covariates. Median follow-up was 30 months. All-cause death was the study end-point. At baseline, restrictive filling pattern and low TAPSE were significant predictors of poor prognosis. At re-evaluation, persistently restrictive/worsened filling pattern, persistently-low/worsened TAPSE and worsened PASP, were associated with poorer survival. A significant interaction between changes in TAPSE, PASP and LV filling pattern was observed: in the restrictive pattern subgroup, survival was poorer in worsened/persistently low TAPSE (p < 0.01); in non-restrictive pattern subgroup, survival was poorer in worsened/persistently elevated PASP (p = 0.01). The re-assessment model improved the C-index from 0.69 to 0.74 (P < 0.01) compared to baseline model. Doppler echocardiographic re-assessment of LV filling pattern, PASP and TAPSE allows a better prognostic stratification of HFrEF outpatients than baseline evaluation and is additional to changes in BNP and NYHA class. • Current heart failure guidelines do not recommend periodically repeating echocardiograms in the follow-up of stable heart failure patients. • Re-assessment of LV filling pattern, PASP and TAPSE allows a better prognostic stratification of HF patients than baseline evaluation. • Echocardiography may thus help clinicians to accurately follow-up heart failure patients. [ABSTRACT FROM AUTHOR]

Background Increased red blood cell distribution width (RDW) has been associated with poor outcome after cardiac resynchronization therapy (CRT). However, whether baseline RDW, and its serial changes after CRT implant, have incremental prognostic value is unknown. Methods and results In 148 consecutive patients (age, 68 ± 9 years; 122 men) undergoing CRT, RDW was assessed before and 3 months after implant. Patients were categorized according to baseline RDW (≤ 14.5% vs > 14.5%); and as “stable”, “decreased”, “increased”, relative to post-implant changes. Primary end-point was a composite of death/HF hospitalization during follow-up (median 21 months). A reduction in left ventricular (LV) end-systolic volume by ≥ 15% at 6-month identified LV reverse remodeling. By multivariable logistic regression analysis “increased” (OR:0.22, 95%CI: 0.07-0.69, P = 0.010) and “stable-high” RDW at follow-up (OR: 0.39, 95%CI: 0.17–0.89, P = 0.027) showed a lower likelihood to develop LV reverse remodeling, while baseline RDW was no longer predictive of LV remodeling. During follow-up, there were 57 events. Baseline RDW > 14.5% (HR: 2.24, 95%CI: 1.05–4.77, P = 0.036), “increased” (HR: 2.55, 95% CI: 1.09–5.97, P = 0.030) and “stable-high” RDW (HR: 2.95, 95% CI: 1.45–5.99, P = 0.003) independently predicted outcome after adjusting for functional improvement after CRT, radial dyssynchrony, BNP, creatinine clearance, and left atrial volume index. However, integrated discrimination improvement and net reclassification improvement were not statistically significant when both baseline RDW and its changes were added to a base predictive model. Conclusion Increased and stable-high values of RDW were independently associated with both LV reverse remodeling and outcome after CRT; however, RDW did not show any incremental predictive value. [ABSTRACT FROM AUTHOR]

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, p<0.0001), 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. • Prognostic determinants in HFpEF hospitalized for acute event are poorly investìgatedE. • 205 HFpEF patients admitted for acute heart failure enrolled; >2 years follow up. • Discharge E/e´ or NT-proBNP predicted events; E/e´ + NT-proBNP refined prediction. • Assessment of E/e´ and NT-proBNP at discharge allows identifying HFpEF at higher risk. [ABSTRACT FROM AUTHOR]