ESC 2022: Can Modern Treatment of Acute Heart Failure Improve (Re)hospitalization Prevention?

The Importance of Understanding the Course of the Disease

Dr. Maria Rosa Costanzo from the Advocate Heart Institute in Naperville stated that each decompensation of HF is a cause of increased mortality from this disease. Acutely decompensated HF (ADHF) is diagnosed in all patients with active worsening of heart failure despite efforts for optimized HF treatment if this worsening requires intensified, escalated, or urgent intravenous, advanced, or rescue HF therapy [1].

ADHF is not specified by location, necessity of hospitalization, or clear presentation. It is always necessary to define hemodynamic subsets (congestive DHF or DHF with hypoperfusion), etiology, phenotypes, and severity, from which the need for specific therapy may arise. Additionally, it is crucial to check the trajectory of response to initial DHF therapy (and potentially proceed with rescue therapy). Good understanding of the clinical course of decompensated HF is key − in this context, the speaker highlighted the expert consensus of the American College of Cardiology from 2019 [2].

Hospitalization for Acute HF and Sacubitril/Valsartan

Professor Michele Senni from the University of Milan emphasized the PIONEER-HF and TRANSITION studies, indicating that they provided numerous insights on the role of the angiotensin receptor and neprilysin inhibitor (ARNI) sacubitril/valsartan, which is one of the four drug groups recommended in heart failure treatment, specifically in acute HF:

• Changes in NT-proBNP concentrations: In PIONEER-HF, significant changes were observed just one week after starting the medication, and the open extension of this study (weeks 8–12) subsequently showed that in a group of patients with HFrEF and recent hospitalization for ADHF, those switched from enalapril to sacubitril/valsartan 8 weeks after randomization had a 37% reduction in NT-proBNP levels [3].
• The TRANSITION study revealed predictors for successful uptitration of sacubitril/valsartan to 200 mg twice daily [4]. Lower success in uptitration of sacubitril/valsartan was observed in patients who initially had chronic kidney disease (CKD) compared to those without CKD.
• Regarding renal safety, the PIONEER-HF study showed no significant differences in the rates of renal function deterioration, hyperkalemia, symptomatic hypotension, or angioedema between sacubitril/valsartan and enalapril [5].
• Biomarkers of myocardial damage and stress (sST2) are elevated in ADHF, and their concentration in the first week post-hospitalization correlates with clinical outcomes. Greater reduction in NT-proBNP levels with sacubitril/valsartan compared to enalapril in the PIONEER-HF study positively reflected in biomarkers and clinical outcomes after discharge [6].
• In high-risk patients, sacubitril/valsartan reduced the incidence of cardiovascular (CV) death or HF rehospitalization (PIONEER-HF study) [5].
• Patients with newly diagnosed HF: In the TRANSITION study, adverse events over 10 weeks occurred in a smaller proportion of de novo patients compared to those with previous HFrEF. Sacubitril/valsartan proved effective as a first-line treatment, with potential to delay progression in de novo patients [7]. The PIONEER-HF study results show that for de novo patients, sacubitril/valsartan remains superior to enalapril regarding NT-proBNP levels and CV death or HF rehospitalization at 8 weeks of treatment [8].

Eva Srbová
proLékaře.cz editorial team

Sources:
1. Costanzo M. R. Putting it all together: drug treatment of acute hospitalised heart failure. Acute hospitalised heart failure: recent positive trials and their clinical relevance, ESC Congress, Barcelona, 2022 Aug 26.
2. Hollenberg S. M., Warner Stevenson L., Ahmad T. et al. 2019 ACC expert consensus decision pathway on risk assessment, management, and clinical trajectory of patients hospitalized with heart failure: a report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol 2019; 74 (15): 1966–2011, doi: 10.1016/j.jacc.2019.08.001.
3. DeVore A. D., Braunwald E., Morrow D. A. et al.; PIONEER-HF Investigators. Initiation of angiotensin-neprilysin inhibition after acute decompensated heart failure: secondary analysis of the open-label extension of the PIONEER-HF trial. JAMA Cardiol 2020; 5 (2): 202−207, doi: 10.1001/jamacardio.2019.4665.
4. Wachter R., Senni M., Bělohlávek J. et al.; TRANSITION Investigators. Initiation of sacubitril/valsartan in haemodynamically stabilised heart failure patients in hospital or early after discharge: primary results of the randomised TRANSITION study. Eur J Heart Fail 2019; 21 (8): 998−1007, doi: 10.1002/ejhf.1498.
5. Velazquez E. J., Morrow D. A., DeVore A. D. et al.; PIONEER-HF Investigators. Angiotensin-neprilysin inhibition in acute decompensated heart failure. N Engl J Med 2019; 380 (6): 539–548, doi: 10.1056/NEJMoa1812851.
6. Morrow D. A., Velazquez E. J., DeVore A. D. et al. Cardiovascular biomarkers in patients with acute decompensated heart failure randomized to sacubitril-valsartan or enalapril in the PIONEER-HF trial. Eur Heart J 2019; 40 (40): 3345–3352, doi: 10.1093/eurheartj/ehz240.
7. Senni M., Wachter R., Witte K. K. et al. Initiation of sacubitril/valsartan shortly after hospitalisation for acutely decompensated heart failure in patients with newly diagnosed (de novo) heart failure: a subgroup analysis of the TRANSITION study. Eur J Heart Fail 2020; 22 (2): 303–312, doi: 10.1002/ejhf.1670.
8. Ambrosy A. P., Braunwald E., Morrow D. A. et al. Angiotensin receptor-neprilysin inhibition based on history of heart failure and use of renin-angiotensin system antagonists. J Am Coll Cardiol 2020; 76 (9): 1034–1048, doi: 10.1016/j.jacc.2020.06.073.
9. Senni M. Acute hospitalized heart failure: sacubitril/valsartan. Acute hospitalised heart failure: recent positive trials and their clinical relevance, ESC Congress, Barcelona, 2022 Aug 26.