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Multicenter Study
. 2022 Apr;9(2):1107-1117.
doi: 10.1002/ehf2.13779. Epub 2022 Feb 5.

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

Frank L Dini  1 , Erberto Carluccio  2 , Roberto Bitto  3 , Michele Ciccarelli  4 , Michele Correale  5 , Andreina D'Agostino  1 , Giuseppe Dattilo  3 , Marco Ferretti  6 , Arianna Grelli  7 , Stefania Guida  7 , Francesca Jacoangeli  2 , Laura Lupi  8 , Lorenzo Luschi  9 , Daniele Masarone  10 , Valentina Mercurio  11 , Giuseppe Pacileo  10 , Nicola Riccardo Pugliese  1 , Antonella Rispoli  4 , Laura Scelsi  7 , Carlo Gabriele Tocchetti  11 , Natale Daniele Brunetti  5 , Alberto Palazzuoli  9 , Massimo Piepoli  12 , Savina Nodari  8 , Giuseppe Ambrosio  2   13 ; Working Group on Heart Failure of the Italian Society of Cardiology
Affiliations
Multicenter Study

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

Frank L Dini et al. ESC Heart Fail. 2022 Apr.

Erratum in

Abstract

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.

Keywords: ejection fraction; haemodynamic; heart failure; prognosis; sacubitril/valsartan.

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Conflict of interest statement

There are no relationships with industry and financial associations from within the past 2 years that might pose a conflict of interest in connection with the submitted article for all the authors.

Figures

Figure 1
Figure 1
Final dosage of sacubitril/valsartan (S/V) according to echo‐defined haemodynamic profile (left panel). Maximal dosage (97/103 mg BID) was more likely reached in Profile‐A, than in other profiles (P = 0.009). (Right panel) Prevalence of patients who withdrew S/V therapy during follow‐up, according to echo‐defined haemodynamic profiles.
Figure 2
Figure 2
Echo‐defined haemodynamic profiles and effects of sacubitril/valsartan (S/V) dosages. (A) Distribution of echo‐defined haemodynamic profiles based on presence/absence of elevated E/e′ ratio and hypoperfusion. CI, cardiac index; E/e′, averaged ratio of early diastolic filling velocity to early diastolic mitral velocity; LVFP, left ventricular filling pressure. (B) Kaplan–Meier failure estimates according to echo‐derived profiles. (C) Treatment effects of S/V therapy according to echo‐defined haemodynamic profiles. Shaded areas represent the 95% confidence intervals for the log‐relative hazard at each baseline echo‐profile.
Figure 3
Figure 3
Left panel: Incidence rate (per 100 patients per year) for the composite of all‐cause death/HF‐related hospitalization, according to echo‐defined haemodynamic profiles. Right panel: univariable hazard ratios (HRs) and 95% confidence intervals for each haemodynamic profile.
Figure 4
Figure 4
Left panel: Incidence rate (per 100 patients per year) for the composite of all‐cause death/heart failure (HF)‐related hospitalization, according to sacubitril/valsartan (S/V) dosages. Central panel: univariable hazard ratios (HRs) and 95% confidence intervals for each S/V dosage; Right panel: Kaplan–Meier failure estimates according to S/V dosages.
Figure 5
Figure 5
Treatment effects of intermediate (left) and high (right) compared with low‐dosage sacubitril/valsartan therapy according to echo‐defined haemodynamic profiles. Shaded areas represent the 95% confidence intervals for the log‐relative hazard at each baseline echo‐profile.
See this image and copyright information in PMC

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