Author + information
- Received September 27, 2019
- Revision received January 2, 2020
- Accepted January 2, 2020
- Published online April 27, 2020.
- Ines Garcia-Lunar, MDa,b,c,
- Isabel Blanco, PhDd,e,
- Leticia Fernández-Friera, PhDa,b,f,
- Susanna Prat-Gonzàlez, PhDg,
- Paloma Jordà, MDg,
- Javier Sánchez, PhDa,h,
- Daniel Pereda, PhDb,g,
- Sandra Pujadas, MDi,
- Mercedes Rivas-Lasarte, PhDi,
- Eduard Solé-Gonzalez, MDj,
- Jorge Vázquez, MDb,k,
- Zorba Blázquez, MDl,
- Juan García-Picart, MDi,
- Pedro Caravaca, MDl,
- Noemí Escalera, BPTa,b,
- Pablo Garcia-Pavia, PhDa,k,m,
- Juan Delgado, PhDb,l,
- Javier Segovia-Cubero, PhDb,k,
- Valentín Fuster, PhDa,n,
- Eulalia Roig, PhDi,
- Joan Albert Barberá, PhDd,e,
- Borja Ibanez, PhDa,b,o,∗∗ ( and )
- Ana García-Álvarez, PhDa,b,g,∗ ( )()
- aCentro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
- bCentro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain
- cHospital Universitario Quirónsalud Madrid, UEM, Madrid, Spain
- dDepartment of Pulmonary Medicine, Hospital Clínic-IDIBAPS, Barcelona, Spain
- eCentro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain
- fHM Hospitales-Centro Integral de Enfermedades Cardiovasculares HM-CIEC, Madrid, Spain
- gInstitut Clinic Cardiovascular, IDIBAPS, Hospital Clínic, University of Barcelona, Barcelona, Spain
- hPhilips Healthcare Iberia, Madrid, Spain
- iCardiology Department, Hospital Santa Creu i Sant Pau, IIb-Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain
- jCardiology Department, Hospital del Mar, Barcelona, Spain
- kCardiology Department, University Hospital Puerta de Hierro, University Autonoma de Madrid, Madrid, Spain
- lCardiology Department, University Hospital 12 de Octubre, Universidad Complutense, Madrid, Spain
- mUniversity Francisco de Vitoria (UFV), Pozuelo de Alarcon, Spain
- nZena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York
- oIIS-Fundación Jiménez Díaz University Hospital, Madrid, Spain
- ↵∗Address for correspondence:
Dr. Ana García-Álvarez, Cardiology Department. Clinic Cardiovascular Institute, Hospital Clínic, Villarroel 170, 08027 Barcelona, Spain.
- ↵∗∗Dr. Borja Ibáñez, Translational Laboratory for Cardiovascular Imaging and Therapy, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Melchor Fernández Almagro, 3. 28029 Madrid, Spain.
• CpcPH is a relatively common complication of chronic HF, is associated with poor survival, and has no specific pharmacological treatment.
• ß3AR stimulation has shown improvement in pulmonary hemodynamics and RV performance in a translational large animal model mimicking this condition.
• The SPHERE-HF trial is a Phase II randomized, double-blind clinical trial designed to evaluate the efficacy and safety of mirabegron (oral β3 AR agonist) in patients with CpcPH secondary to HF.
• The SPHERE-HF trial will include 80 patients treated with mirabegron or placebo for 16 weeks.
• The main outcome is the change in PVR. Secondary outcomes include changes in RV performance, clinical status, NT-proBNP levels, and additional pulmonary hemodynamic parameters.
Combined pre-and post-capillary hypertension (CpcPH) is a relatively common complication of heart failure (HF) associated with a poor prognosis. Currently, there is no specific therapy approved for this entity. Recently, treatment with beta-3 adrenergic receptor (β3AR) agonists was able to improve pulmonary hemodynamics and right ventricular (RV) performance in a translational, large animal model of chronic PH. The authors present the design of a phase II randomized clinical trial that tests the benefits of mirabegron (a clinically available β3AR agonist) in patients with CpcPH due to HF. The effect of β3AR treatment will be evaluated on pulmonary hemodynamics, as well as clinical, biochemical, and advanced cardiac imaging parameters. (Beta3 Agonist Treatment in Chronic Pulmonary Hypertension Secondary to Heart Failure [SPHERE-HF]; NCT02775539)
The SPHERE-HF trial is an investigator-initiated noncommercial trial independent of the pharmaceutical industry. This work was funded by a grant from Fundació La Marató de TV3 (20151730-31-32). The CNIC is supported by the Ministerio de Ciencia, Innovación y Universidades and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505). IDIBAPS belongs to the CERCA Programme and receives partial funding from the Generalitat de Catalunya. Drs. Ibanez, García-Álvarez, and Fuster are co-inventors of a patent for the use of beta-3 agonists for the treatment of pulmonary hypertension. 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: Basic to Translational Science author instructions page.
- Received September 27, 2019.
- Revision received January 2, 2020.
- Accepted January 2, 2020.
- 2020 The Authors