Benefit from sacubitril/valsartan is associated with hemodynamic improvement in heart failure with reduced ejection
Erberto Carluccio1, Frank L Dini2, Roberto Bitto3
1Cardiology and Cardiovascular Pathophysiology, University of Perugia, Italy.
Insights
Sacubitril/valsartan improves heart failure outcomes by enhancing hemodynamic profiles in patients with reduced ejection fraction. Improved hemodynamics are linked to better prognosis, independent of ejection fraction.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Medicine
Background:
- Sacubitril/valsartan demonstrates improved outcomes in heart failure with reduced left ventricular ejection fraction (HFrEF).
- Mechanisms underlying sacubitril/valsartan's benefits in HFrEF remain incompletely understood.
- Echocardiographic hemodynamic profiles offer a potential window into treatment effects.
Purpose of the Study:
- To evaluate the impact of sacubitril/valsartan on echocardiographically derived hemodynamic profiles.
- To determine the association between changes in hemodynamic profiles and patient outcomes.
Main Methods:
- A multicenter, open-label study involving 727 HFrEF outpatients.
- Comprehensive echocardiography performed at baseline and 12 months to assess left ventricular filling pressure (E/e') and cardiac index (CI).
- Patients categorized into four hemodynamic profiles (A, B, C, D); changes and associations with death/HF-hospitalization assessed via multivariable Cox analysis.
Main Results:
- After 12 months, 53% of patients showed improved hemodynamic profiles, with prevalence increasing with sacubitril/valsartan dose.
- Patients with improved profiles experienced significantly lower rates of death/HF-hospitalization compared to those with unchanged or worsened profiles.
- Improved hemodynamic profile was an independent predictor of favorable outcomes (HR 0.65, P < 0.05).
Conclusions:
- Sacubitril/valsartan treatment leads to significant improvements in hemodynamic profiles in HFrEF patients.
- These hemodynamic improvements are closely associated with the drug's beneficial prognostic effects.
- Hemodynamic profile changes offer valuable insights into sacubitril/valsartan's mechanism of action in heart failure.
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.
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