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Targeting Cyclic Guanosine Monophosphate to Treat Heart Failure: JACC Review Topic of the Week

Research output: Contribution to journalReview article

Michele Emdin, Alberto Aimo, Vincenzo Castiglione, Giuseppe Vergaro, Georgios Georgiopoulos, Luigi Francesco Saccaro, Carlo Mario Lombardi, Claudio Passino, Elisabetta Cerbai, Marco Metra, Michele Senni

Original languageEnglish
Pages (from-to)1795-1807
Number of pages13
JournalJournal of the American College of Cardiology
Issue number15
Published13 Oct 2020

King's Authors


The significant morbidity and mortality associated with heart failure with reduced ejection fraction (HFrEF) or heart failure with preserved ejection fraction (HFpEF) justify the search for novel therapeutic agents. Reduced cyclic guanosine monophosphate levels contribute to HF progression. Among molecules modulating the nitric oxide (NO)–GMP–phosphodiesterase (PDE) pathway, the evaluation of nitrates, synthetic natriuretic peptides (NP), and NP analogs has yielded mixed results. Conversely, sacubitril/valsartan, combining NP degradation inhibition through neprilysin and angiotensin receptor blockade, has led to groundbreaking findings in HFrEF. Other strategies to increase tissue cyclic guanosine monophosphate have been attempted, such as PDE-3 or PDE-5 inhibition (with negative or neutral results), NO-independent soluble guanylate cyclase (sGC) activation, or enhancement of sGC sensitivity to endogenous NO. Following the positive results of the phase 3 VICTORIA (A Study of Vericiguat in Participants With Heart Failure With Reduced Ejection Fraction) trial on the sGC stimulator vericiguat in HFrEF, the main open questions are the efficacy of the sacubitril/valsartan-vericiguat combination in HFrEF and of vericiguat in HFpEF.

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