Author + information
- Received May 26, 2020
- Revision received August 13, 2020
- Accepted August 14, 2020
- Published online October 5, 2020.
- Michele Emdin, MD, PhDa,b,∗∗ ( )(, )@MicheleEmdin,
- Alberto Aimo, MDa,∗,
- Vincenzo Castiglione, MDa,
- Giuseppe Vergaro, MD, PhDa,b,
- Georgios Georgiopoulos, PhDc,
- Luigi Francesco Saccaro, MDa,
- Carlo Mario Lombardi, MD, PhDd,
- Claudio Passino, MDa,b,
- Elisabetta Cerbai, MD, PhDe,
- Marco Metra, MDd and
- Michele Senni, MDf
- aInstitute of Life Sciences, Scuola Superiore Sant’Anna, Pisa, Italy
- bCardiology Division, Fondazione Toscana Gabriele Monasterio, Pisa, Italy
- cSchool of Biomedical Engineering and Imaging Sciences, King’s College London, London, United Kingdom
- dDepartment of Medical and Surgical Specialties, Radiological Sciences, and Public Health University and Civil Hospital, Brescia, Italy
- eDepartment of Neurosciences, Psychology, Drug Research and Child Health, Center for Molecular Medicine, University of Florence, Florence, Italy
- fCardiovascular Department and Cardiology Unit, Azienda Socio-Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy
- ↵∗Address for correspondence:
Dr. Michele Emdin, Institute of Life Sciences, Scuola Superiore Sant’Anna, Piazza Martiri della Libertà 33, 56124 Pisa, Italy.
• Levels of cGMP are often reduced in patients with HF.
• Several drugs modulating NO-GMP-PDE pathways have been evaluated as potential therapeutic avenues for HF.
• Sacubitril/valsartan and vericiguat are associated with beneficial effects on prognosis in patients with HF.
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.
↵∗ Drs. Emdin and Aimo contributed equally to this work.
Dr. Emdin has received consulting fees from Merck; and serves as an Italian national leader investigator of VICTORIA. Dr. Metra has received consulting fees from Bayer, Fresenius, Novartis, and Windtree Therapeutics for participation on Advisory Boards or Executive Committees of clinical trials. Dr. Senni has received consulting fees from Bayer, Merck, Novartis, Vifor Pharma, Abbott, Boehringer Ingelheim, AstraZeneca, BioVentrix, and Servier; and serves as an Italian national leader investigator of VICTORIA. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC author instructions page.
- Received May 26, 2020.
- Revision received August 13, 2020.
- Accepted August 14, 2020.
- 2020 American College of Cardiology Foundation
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