Low- and High-renin Heart Failure Phenotypes with Clinical Implications

Author:

Pavo Noemi1,Goliasch Georg1,Wurm Raphael1,Novak Johannes1,Strunk Guido2,Gyöngyösi Mariann1,Poglitsch Marko3,Säemann Marcus D4,Hülsmann Martin1

Affiliation:

1. Department of Internal Medicine II, Clinical Division of Cardiology, Medical University of Vienna, Vienna, Austria

2. Complexity Research, Vienna, Austria; FH Campus Vienna, Vienna, Austria, and Technical University Dortmund, Dortmund, Germany

3. Attoquant Diagnostics, Vienna, Austria

4. Department of Internal Medicine III, Clinical Division of Nephrology, Medical University of Vienna, Vienna, Austria

Abstract

Abstract BACKGROUND Blockade of the renin–angiotensin system (RAS) represents a main strategy in the therapy of heart failure with reduced ejection fraction (HFrEF), but the role of active renin concentration (ARC) for guiding therapy in the presence of an RAS blockade remains to be established. This study assessed angiotensin profiles of HFrEF patients with distinct RAS activations as reflected by ARC. METHODS Two cohorts of stable chronic HFrEF patients on optimal medical treatment (OMT) were enrolled. We assessed ARC and all known circulating angiotensin metabolites, including AngI and AngII, by mass spectrometry to investigate the effect of different therapy modalities. Low- and high-renin HFrEF patients were identified by ARC screening and subsequently characterized by their angiotensin profiles. RESULTS Although different modes of RAS blockade resulted in typical AngII/AngI ratios, concentrations of (AngI+AngII) strongly correlated with ARC [r = 0.95, P < 0.001] independent of therapy mode. Despite RAS blocker treatment with angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin II type 1 receptor blockers (ARB), which anticipated ARC upregulation, about 30% of patients showed lower/normal range ARC values. ARC did not correlate with N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations and New York Heart Association (NYHA) stages. Angiotensin concentrations were profoundly diminished for the low-ARC group compared with the high-ARC group: AngI [6.4 ng/L (IQR: 2.1–12.5) vs 537.9 ng/L (IQR: 423.1–728.4), P < 0.001 for ACE-I; and 4.5 ng/L (IQR: 1.4–11.2) vs 203.0 ng/L (IQR: 130.2–247.9), P = 0.003 for ARB] and AngII [<1.4 ng/L (IQR: <1.4–1.5) vs 6.1 ng/L (IQR: 2.0–11.1), P = 0.002 for ACE-I and 4.7 ng/L (IQR: <1.4–12.3) vs 206.4 ng/L (IQR: 142.2–234.4), P < 0.001 for ARB]. CONCLUSIONS In addition to NT-proBNP and NYHA stages, ARC enables classification of HFrEF patients receiving OMT into more distinguished neurohumoral HFrEF phenotypes, offering a rationale for adaptive therapeutic interventions.

Publisher

Oxford University Press (OUP)

Subject

Biochemistry, medical,Clinical Biochemistry

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