Table 1.

Inclusion and exclusion criteria for recruited patients

Inclusion criteria
Demographic criteria
Sex	Male and female
Age	≥18 years old
Population	Diagnosed of HF, NYHA functional classes II–III, with ≥ a 3-month duration at the inclusion. Stable under HF therapy
Anthropometric criteria
Body mass index	19–30 kg/m2
Medical criteria
	Laboratory analysis results, vital signs, and ECG were performed to validate that the inclusion criteria were met
Medication criteria
History	Must be under stable drug therapy, defined as no new drug for HF introduced within 4 weeks prior to inclusion
Other criteria
Procedures	Informed consent approved by the ethics committee of the HSCSP signed by patients before any intervention
Pregnancy	Women not pregnant and assure no risk of pregnancy
Exclusion criteria
Medical criteria
Hospitalization	Hospitalization due to HF, any acute cardiac disease or procedure within the previous 6 weeks or any major surgery within the previous 8 weeks
Concomitant clinical conditions	Symptoms of angina at rest or with minimal activity (class III or IV, Canadian Cardiovascular Society) Severe aortic or mitral stenosis or clinically significant valvular heart disease that could lead to surgery within 12 months after inclusion Hypertrophic obstructive cardiomyopathy, active myocarditis, constrictive pericarditis, or clinically significant congenital heart disease Hepatitis B, hepatitis C or HIV or AIDS diagnosis Medical history or evidence of drug or alcohol abuse in the 3 months prior to inclusion Concomitant cardiovascular disease that was expected to reduce life expectancy to less than 1 year, or uncontrolled insulin-dependent diabetes SBP >150 mmHg, DBP >95 mmHg, HR in supine ≥100 beats/min after a 5-minute rest or untreated symptomatic bradycardia within 1 month prior to inclusion Total bilirubin ≥1.5 times ULN, or ALT or AST ≥3 times ULN, and estimated GFR ≤30 mL/min/1.73 m2
Ventricular assist devices	To require ventricular assist devices, underwent CRT within 3 months or cardioverter defibrillator in the 4 weeks prior to inclusion
Transplants	To have a main organ transplant or a high probability of receiving a heart transplant within 6 months after inclusion
Medication criteria
Concomitant therapy	Scheduled routine intravenous infusions for HF (eg, inotropes, vasodilators, diuretics) or routine ultrafiltration Digoxin therapy at a steady state exceeding 1.0 ng/mL at inclusion Current intake of a potent inhibitor of CYP2C9 or within 14 days prior to inclusion Current intake of a potent inducer of CYP2C9 or within 28 days prior to inclusion Chronic therapy with antiepileptic and antiarrhythmic drugs (except beta blockers) Treatment with eplerenone and espironolactone was only permitted after 7 days of washout Amiodarone was only permitted after 14 days of washout Chronic treatment (>7 days) with NSAIDs, except aspirin ≤325 mg dose
Other criteria
	Participation in other clinical trials within the preceding 60 days, or five half-lives before inclusion Blood donation during 4 weeks prior to inclusion

Abbreviations: CRT, cardiac resynchronization therapy; ECG, electrocardiogram; NSAIDs, nonsteroidal anti-inflammatory drugs; GFR, glomerular filtration rate; HF, heart failure; NYHA, New York Heart Association; HSCSP, Hospital de la Santa Creu i Sant Pau; SBP, systolic blood pressure; DBP, diastolic blood pressure; HR, heart rate; ULN, upper normal limit; ALT, alanine aminotransferase; AST, aspartate aminotransferase.