Virtual Human Twins as Tools for Personalized Clinical Care in Heart Failure With Preserved Ejection Fraction: a Pilot Study

Prior treatment

• Treatment with an approved MRA (e.g., spironolactone, eplerenone, finerenone) for more than 7 days within the last month prior to screening
• Systolic blood pressure \<100 mmHg or symptomatic hypotension within the previous 24 hours
• Acute coronary syndrome, stroke, or transient ischemic attack within the 3 months before screening
• Major cardiac surgery, coronary revascularization, or valvular repair within 3 months prior to screening
• Renal replacement therapy within the previous 4 weeks or requirement for renal replacement therapy
• Receiving medication that is contraindicated to excessive light exposure (in order to exclude the possibility of local skin irritation from irradiation by LED-light of PPG)

Other illness

• Hypersensitivity to spironolactone
• History of obstructive hypertrophic cardiomyopathy, infiltrative cardiomyopathy (including amyloidosis), restrictive, or arrhythmogenic right ventricular cardiomyopathy
• Active myocarditis or pericardial causes of heart failure
• History of mechanical circulatory support or heart transplantation
• Severe liver disease or Addison's disease
• Any contraindication to cardiac MRI: severe claustrophobia, any device which is known to threaten or pose hazard in all magnetic resonance environments (as defined on //www.mrisafety.com/, patients with implanted biomedical devices (cardiac artefacts): pacemakers, cardiac defibrillators or cardiac resynchronization therapy
• Allergy to gadolinium
• Known allergies to adhesives and/or Ag/AgCl electrodes and/or metals and/or plastic

Lab values

• Serum potassium \> 5 mmol/l at screening
• History of severe hyperkalemia (i.e., ≥ 6 mmol/l)
• LVEF \< 40% or alternative primary cardiac diagnosis explaining symptoms (significant valvular disease requiring intervention, hypertrophic or infiltrative cardiomyopathy, constrictive pericarditis)

Other

• Estimated glomerular filtration rate \< 30 mL/min/1.73 m² at screening
• Systolic blood pressure ≥180 mmHg regardless of treatment, at the time of screening
• Severe comorbidity with life expectancy \< 1 year
• Inability to perform exercise testing (including VO2max), as determined by the physician
• Pregnancy or breastfeeding
• Individuals suffering from skin irritation or non-intact skin at the sensor attachment sites (sternum, chest, left upper arm, and index, middle or ring finger)
• Individuals under legal protection or guardianship
• Inability to understand the study procedures
• Patient under State Medical Aid (AME)

• Age ≥18 years and ≤ 90 years
• Prior diagnosis of HF with LVEF \> 40%, documented by echocardiography performed within the 6 months before screening
• Patient already treated with an SGLT2 inhibitor for HF for at least 4 weeks at a stable dose, as part of routine clinical care
• With an indication to receive spironolactone for HF, as part of routine clinical care (i.e., not an experimental treatment introduced for the purpose of this study), at the guideline-recommended starting dose, i.e., 25 mg once daily
• For patients in sinus rhythm, NT-proBNP levels ≥ 300 pg/ml; for patients in atrial fibrillation, NT-proBNP levels ≥ 600 pg/ml at screening
• Affiliated with a social security scheme
• Physical condition compatible with the performance of study-related investigations, as judged by the investigator
• Patient who has provided written informed consent
• Willingness to shave the electrode attachment sites if necessary