Table 1.

Inclusion and Exclusion Criteria

Inclusion Criteria	Exclusion Criteria
Written informed consent	Noncoronary cardiac surgery (e.g., valvular surgery) or noncoronary structural percutaneous procedure (e.g., Mitraclip) within the 12 months preceding recruitment or scheduled.
Age ≥18 years of age	Myocardial infarction or coronary revascularization within the 3 months preceding recruitment.
HF with reduced, intermediate or preserved LVEF, according to the definition of the European Society of Cardiology guidelines.	CRT implantation within the 6 months preceding recruitment
Combined pre- and post-capillary PH determined by RHC showing the following:
PCWP or LVEDP ≥15 mm Hg. Mean PAP ≥25 mm Hg; and: PVR ≥3 WU and/or diastolic gradient ≥7 mm Hg, or transpulmonary gradient ≥12 mm Hg	Sinus tachycardia or uncontrolled atrial fibrillation (HR >100 beats/min).
NYHA functional class II−IV	Uncontrolled systemic hypertension (systolic BP >180 mm Hg or diastolic BP >110 mm Hg) or symptomatic hypotension (systolic BP <90 mm Hg).
On optimized evidence-based pharmacological treatment	Diagnosis of infiltrative cardiomyopathy.
Stable clinical condition defined as no changes in therapeutic regimen for HF or hospitalization in the 30 days preceding recruitment and no current plan for changing therapy.∗	Pre-menopausal women who have not undergone total hysterectomy
	Expected survival <1 yr due to a disease other than HF.
	Severe renal failure (GFR <30 ml/min/1.73 m2).
	Severe hepatic impairment (transaminase elevation>3 times ULN).
	Prolonged QTc interval on the ECG (>430 ms in men or >450 ms in women)†
	Concomitant use with specific pulmonary vasodilators (sildenafil, bosentan, macicentan, riociguat, or other endothelin receptor blockers, phosphodiesterase 5 inhibitors or guanylate cyclase stimulators).
	Treatment with digoxin, flecainide, propafenone, dabigatran, tricyclic antidepressants or other CYP2D6 inhibitors (other than β-blockers).
	Severe COPD (FEV1/FVC ratio <0.7 together with FEV1 <50% predicted value).
	Severe restrictive lung disease (TLC <50%)
	Participation in another clinical trial
	Known allergy to mirabegron or any of the excipients

BP = blood pressure; COPD = chronic obstructive pulmonary disease; CRT = cardiac resynchronization therapy; FEV1 = forced expiratory volume in the first second; FVC = forced vital capacity; GFR = glomerular filtration rate; HR = heart rate; LVEDP = left ventricular end-diastolic pressure; NYHA = New York Heart Association; PAP = pulmonary artery pressure; PCWP = pulmonary capillary wedge pressure; PVR = pulmonary vascular resistance; RHC = right heart catheterization; TLC = total lung capacity; ULN = upper limit of normal; WU = Wood units.

^∗In the case of heart failure (HF) with preserved left ventricular ejection fraction (LVEF) it refers to an adequate control of comorbidity and optimized fluid status.

^†This criterion was changed by an amendment to QTc >480 ms.