Search

Aim: Echo‐derived haemodynamic classification, based on forward‐flow and left ventricular (LV) filling pressure (LVFP) correlates, has been proposed to phenotype patients with heart failure and reduced ejection fraction (HFrEF). To assess the prognostic relevance of baseline echocardiographically defined haemodynamic profile in ambulatory HFrEF patients before starting sacubitril/valsartan. Methods and results: In our multicentre, open‐label study, HFrEF outpatients were classified into 4 groups according to the combination of forward flow (cardiac index; CI:< or ≥2.0 L/min/m2) and early transmitral Doppler velocity/early diastolic annular velocity ratio (E/e′: ≥ or <15): Profile‐A: normal‐flow, normal‐pressure; Profile‐B: low‐flow, normal‐pressure; Profile‐C: normal‐flow, high‐pressure; Profile‐D: low‐flow, high‐pressure. Patients were started on sacubitril/valsartan and followed‐up for 12.3 months (median). Rates of the composite of death/HF‐hospitalization were assessed by multivariable Cox proportional‐hazards models. Twelve sites enrolled 727 patients (64 ± 12 year old; LVEF: 29.8 ± 6.2%). Profile‐D had more comorbidities and worse renal and LV function. Target dose of sacubitril/valsartan (97/103 mg BID) was more likely reached in Profile‐A (34%) than other profiles (B: 32%, C: 24%, D: 28%, P < 0.001). Event‐rate (per 100 patients per year) progressively increased from Profile‐A to Profile‐D (12.0%, 16.4%, 22.9%, and 35.2%, respectively, P < 0.0001). By covariate‐adjusted Cox model, profiles with low forward‐flow (B and D) remained associated with poor outcome (P < 0.01). Adding this categorization to MAGGIC‐score and natriuretic peptides, provided significant continuous net reclassification improvement (0.329; P < 0.001). Intermediate and high‐dose sacubitril/valsartan reduced the event's risk independently of haemodynamic profile. Conclusions: Echocardiographically‐derived haemodynamic classification identifies ambulatory HFrEF patients with different risk profiles. In real‐world HFrEF outpatients, sacubitril/valsartan is effective in improving outcome across different haemodynamic profiles. [ABSTRACT FROM AUTHOR]

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]