From: Heart failure with preserved ejection fraction based on aging and comorbidities
Types | Interventions | Inclusion | Trials | Endpoints | Results |
---|---|---|---|---|---|
Exercise | Exercise training | NYHA II-III, EF ≥ 50%, tissue Doppler-derived E/e' ratio | Ex-DHF | Exercise capacity, QOL | Positive |
ACEI/ARB | Candesartan | Aged ≥ 18 years, NYHA II-IV, EF > 40% | CHARM-Preserved | CV death, HF hospitalization | Neutral |
 | Perindopril | Aged ≥ 70 years, clinical diagnosis of chronic HF, EF ≥ 40%, hospitalised for a cardiac problem, able to walk without the aid of another person | PEP-CHF | CV death, HF hospitalization | Neutral |
ARNI | Sacubitril/valsartan | Aged ≥ 40 years, EF ≥ 45%, HF signs or symptoms, NT-proBNP ≥ 400 pg/mL, eGFR ≥ 30 mL/min/1.73m2, potassium ≤ 5.2 mmol/L | PARAMOUNT | NT-proBNP | Positive |
 |  | Aged ≥ 45 years, EF > 40%, LAE or LVH on echocardiography, NYHA II–IV, NT-proBNP > 220 pg/mL for patients with no AF or > 600 pg/mL for those with AF | PARALLAX | NT-proBNP | Positive |
sGC stimulator and activator | Vericiguat | Aged ≥ 45 years, EF ≥ 45%, NYHA II–III, HF decompensation, NT-proBNP ≥ 300 or BNP ≥ 100 pg/mL in sinus rhythm, or NT-proBNP ≥ 600 or BNP ≥ 200 pg/mL in AF, LVH (intraventricular septal or posterior wall thickness ≥ 1.1 cm, and/or LVMI ≥ 115 g/m2 in male and ≥ 95 g/m2 in female), or LAE (LAV index ≥ 29 mL/m2, or LAV > 58 mL in male and > 52 mL in female patients, or LA area > 20 cm2, or LA diameter > 40 mm in male and > 38 mm in female patients) | VITALITY | QOL | Positive |
 |  | NYHA II-IV, EF ≥ 45%, BNP ≥ 100 pg/mL or NT-proBNP ≥ 300 pg/mL(or BNP ≥ 200 pg/mL or NTproBNP ≥ 600 pg/mL in AF), LAE determined by echocardiography | SOCRATES-PRESERVED | QOL | Neutral |
 | Riociguat | EF ≤ 35%, NYHA Class III-IV | DYNAMIC | CO | Positive |
SGLT-2 inhibitor | Empaglifozin | NYHA II-IV, EF > 40%, NT-proBNP > 300 pg/mL in patients without AF and > 900 pg/mL in AF, structural changes in the heart (left atrial size or LVM) on echocardiography, HF hospitalization | EMPEROR-PRESERVED | CV death, HF hospitalization | Positive |
 |  | EF > 40%, NYHA II-IV, 6MWD of ≥ 100 m and ≤ 350 m | EMPERIAL-PRESERVED | 6MWD | Positive |
 | Sotaglifozin | Type 2 diabetes mellitus, HF hospitalization | SOLOIST-WHF | CV death, HF hospitalization | Positive |
Nitrate | Oral nitrate | Mean PAP ≥ 35 mmHg and baseline PCWP ≥ 20 mmHg, NYHA II-III, EF ≥ 40% | PH-HFPEF | PAP at exercise | Positive |
MRA | Spironolactone | Aged ≥ 50 years, EF ≥ 45%, potassium < 5.0 mmol/L, HF hospitalization, BNP ≥ 100 pg/ml, NT-proBNP ≥ 360 pg/ml | TOPCAT | HF hospitalization | Neutral |
 |  | Aged ≥ 50 years, NYHA II-III, EF 50%, diastolic dysfunction | Aldo-DHF | Neurohumoral activation, LVH | Positive |
PDE-5 inhibitor | Sildenafl | Outpatients with HFpEF | RELAX | PAP, CO | Positive |
Pirfenidone | Pirfenidone | Aged ≥ 40 years, EF ≥ 45%, symptoms and signs of HF, BNP ≥ 100 pg/ml or NT-proBNP ≥ 300 pg/ml(patients in AF are required to have BNP ≥ 300 pg/ml or NT-proBNP ≥ 900 pg/ml) | PIROUETTE | ECV | Positive |
Cardiolipin peroxidase inhibitor | Elamipretide | Aged 40–80 years, EF ≤ 40%, no hospitalization related to HF, at least 3 dysfunctional but viable segments (hyperenhancement ≤ 25%) by cardiac MRI examination | PROGRESS-HF | NT-pro-BNP | Positive |
Beta3-adrenoreceptor selective agonist | Mirabegron | LVH (increased LVMI or LVWT ≥ 13 mm in at least one wall segment), in the absence of genetic hypertrophic cardiomyopathy and significant valvular disease | BETA3-LVH | LVMI, E/e′ | Positive |
Device therapy | CardioMEMS | NYHA II-IV regardless of EF with and elevated natriuretic peptides | GUIDE-HF | All-cause death, HF hospitalization | Positive |
 |  | HF ≥ 3 months, NYHA class III | CHAMPION | HF hospitalization | Positive |
 | IASD | EF ≥ 40% and NYHA III-IV HF, PCWP ≥ 15 mmHg at rest or ≥ 25 mmHg during supine bike exercise | REDUCE LAP-HF | CV death, HF hospitalization | Positive |
 | ASV | HFpEF or HFrEF, AHI ≥ 15 events per hour | CAT HF | CV death, HF hospitalization, 6MWD | Positive |