Echocardiographically defined haemodynamic categorization predicts prognosis in ambulatory heart failure patients treated with sacubitril/valsartan.

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.

Benefit from sacubitril/valsartan is associated with hemodynamic improvement in heart failure with reduced ejection fraction: An echocardiographic study.

BACKGROUND: 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. PURPOSE: To assess changes in echocardiographically-derived hemodynamic profiles induced by sacubitril/valsartan and their impact on outcome. METHODS: 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. RESULTS: 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). CONCLUSION: In HFrEF patients, the beneficial prognostic effects of sacubitril/valsartan are associated with improvement in hemodynamic conditions.

Trend of perceived quality of life and functional capacity in outpatients with chronic heart failure and in treatment with sacubitril/valsartan: a real-life experience.

BACKGROUND: Despite the use of optimal medical therapy, heart failure and reduced left ventricular ejection fraction (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 HFrEF. 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. METHODS: 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, NT-ProBNP, BNP and NYHA class. However, analyzing the ∆% 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.

Diagnosis of type 2 Brugada pattern: insights from a pilot survey.

BACKGROUND: Differentiation of Type 2 Brugada Pattern (BP) from incomplete right bundle branch block or normal rSr' pattern can be insidious. The aim of this study was to assess interobserver and intraobserver agreement in the diagnosis of type 2 BP in a cohort of cardiologists with different skills. METHODS: We collected 14 ECGs with a positive terminal deflection of the QRS complex in lead V1 and V2 at the 4th intercostal space. We proposed these ECGs, specifying to use 2012 Consensus conference criteria for diagnosis of type 2 BP, to 42 participants: 14 arrhythmologists, 14 general cardiologists and 14 electrophysiology (EP) fellows. The same 14 ECGs, with a different order, were proposed fifteen days later to the same cohort to assess intraobserver variability. Authors analyzed all 14 ECGs in order to assess whether 2012 Consensus Conference criteria for BP were fulfilled. All patients underwent provocative test with IC antiarrhythmics drugs (flecainide) in order to exclude or confirm the diagnosis of Brugada Syndrome (BrS). RESULTS: Slight interobserver agreement (Fleiss K<0.20) in the diagnosis of type 2 BP was observed in all three categories of cardiologists. Considering five operators per class, intraobserver agreement is variable (k ranging from 0.000 to 0.857), with a slight superiority of arrhytmologists (k minimum value 0.276; k maximum value 0.857). CONCLUSIONS: This study demonstrated, for the first time, a low interobserver agreement in diagnosis of type 2 BP in categories of cardiologists with different abilities. Reproducibility of type 2 BP diagnosis (intraobserver agreement) is poor, even among experts. These findings highlight the difficulties in analysis of ECG with BrS suspicion and, therefore, underscore the key role of clinical and anamnestic data.

Cardiovascular Risk in Psoriasis: Current State of the Art.

Psoriasis (Pso) is a chronic inflammatory immune-mediated skin disease associated with several comorbidities. Despite the growing number of studies providing evidence for the link between Pso and Cardiovascular (CV) disorders, there are still many unsolved questions, dealing with the role of the skin disease as an independent risk factor for CV events, the influence of Pso severity and duration on CV damage, the presence of Psoriatic Arthritis (PsA) as a predictor of increased CV mortality and morbidity and the detection of reliable clinical, laboratory and/or instrumental parameters to stratify CV risk in psoriatic patients. Moreover, it remains to clarify if the early treatment of the dermatosis may lower CV risk. In this paper we will try to provide answers to these queries in the light of the updated data of the literature.