Author + information
- Pardeep Jhund,
- Jean Rouleau,
- Karl Swedberg,
- Michael Zile,
- Martin Lefkowitz,
- Margaret Prescott,
- Victor Shi,
- Scott Solomon,
- Milton Packer and
- John McMurray
Background: Urinary cyclic guanosine monophosphate (ucGMP) levels reflect the activity of vasoactive substances (eg B-type natriuretic peptide (BNP)). The ucGMP/BNP ratio is lower in heart failure (HF) and is associated with worse prognosis. We examined the relationship between ucGMP/BNP and outcomes, and the effect of sacubitril/valsartan (sac/val) on the ratio, in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF).
Methods: The association between ucGMP/BNP ratio and cardiovascular death or HF hospitalization (CV/HFH) and CV death was examined, as was the effect of sac/val (vs enalapril) on the ucGMP/BNP ratio.
Results: In 2031 with ucGMP/BNP, low ucGMP/BNP was associated with a higher risk of CV/HFH (31% vs 16% in the lowest vs highest tertile) and CV death (17% vs 8%). The risk of CV/HFH in compared to tertile 1 (lowest cGMP/BNP ratio), was HR=0.44(0.35 −0.55) in tertile 3 (highest cGMP/BNP ratio). This was similar for CV death. Sac/val (vs enalapril) caused the ucGMP/BNP ratio to rise (Figure). The effect of sac/val on outcomes was not modified by ucGMP/BNP ratio at randomization (p interaction CV death/HFH=0.90)
Conclusions: Lower cGMP/BNP ratio is associated with worse outcomes in patients with HF. Neprilysin inhibition with sac/val increased the cGMP/BNP ratio more than enalapril, likely reflecting the potentiation of other peptides acting through the cGMP signalling pathway to promote vasodilation and natriuresis.
Moderated Poster Contributions
Heart Failure and Cardiomyopathies Moderated Poster Theater, Poster Hall, Hall C
Friday, March 17, 2017, 3:45 p.m.-3:55 p.m.
Session Title: Hormones and Heart Failure
Abstract Category: 13. Heart Failure and Cardiomyopathies: Clinical
Presentation Number: 1177M-03
- 2017 American College of Cardiology Foundation