Evaluation of GeranylGeranylAcetone in Heart Failure With Preserved Ejection Fraction

Prior treatment

• Acute coronary syndrome, transient ischemic attack/cerebrovascular accident, major surgery within the previous 3 months
• Acute myocarditis within 3 months prior to randomization
• Currently enrolled in another investigational device or drug trial

Other illness

• Current acute decompensated heart failure, requiring hospitalization or augmented therapy with intravenous diuretics, vasodilators, and/or inotropic drugs
• History of mitral valve repair or replacement
• Presence of significant valvular disease defined as mitral valve regurgitation defined as grade ≥ 3+ MR; tricuspid valve regurgitation defined as grade ≥ 2+ TR; aortic valve disease defined as ≥ 2+ AR or \> moderate AS
• Severe pulmonary disease requiring home oxygen or chronic oral steroid therapy
• Precapillary pulmonary hypertension
• History of solid organ transplantation including kidney transplantation
• Proven allergy for lactose products or cow-milk.
• Proven allergy for Iodide-containing contrast, Iohexol or PAH.
• Any documented or suspected malignancy or history of malignancy within 1 year prior to screening, except appropriately treated basal cell carcinoma of the skin or in situ carcinoma of the cervix

Lab values

• Hemoglobin \<9 g/dl at screening
• LVEF \<40% measured at any time point in the history of the patient
• Estimated glomerular filtration rate (GFR) \<20 ml/min or \>90 ml/min

Other

• Infiltrative cardiomyopathy
• Genetic cardiomyopathy
• BMI \>40 kg/m2
• Atrial fibrillation or atrial flutter with resting ventricular rate \>110 bpm
• Not able to undergo the complete study protocol
• Doubt about compliance
• Pre-menopausal women who are nursing, pregnant, or of child-bearing potential and not practicing an acceptable method of birth control
• Chronic absorption problems
• Estimated life expectancy \<1 year

• Age≥ 50 years
• Patients with a diagnosis of symptomatic chronic heart failure (New York Heart Association class II or III) AND preserved systolic LV function (LV ejection fraction or LVEF ≥ 50%) documented within the last 6 months AND evidence of diastolic LV dysfunction with at least 1 out of the following 4 criteria:
  • HFA-PEFF score ≥5
  • H2FPEF score ≥6
  • HFpEF according to the 2021 ESC HF Guidelines (NT-proBNP\>125 pg/ml AND either LV mass indexed or LVMI \>95 g/m2 for women and \>115 g/m2 for men OR left atrial volume indexed or LAVI \>34 ml/m2 OR mean e; septal/lateral \< 9 cm/s) OR E/e' \>13 OR TR velocity at rest \>2,8m/s.
  • Pulmonary capillary wedge pressure (PCWP) \>15 mmHg and/or \>25 mmHg during exercise.