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Table 1 Trials of exercise, medications and devices in patients with HFpEF

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

  1. HFpEF heart failure with preserved ejection fraction, NYHA New York Heart Assocation, AF atrial fibrillation, QOL quality of life, 6MWD 6-min walk distance, ACEI angiotensin-converting enzyme inhibitor, ARB angiotensin receptor blocker, ARNI angiotensin receptor-neprilysin inhibitor, eGFR estimated glomerular filtration rate, CV cardiovascular, BNP B-type natriuretic peptide, NT-proBNP N-terminal pro-B-type natriuretic peptide, sGC soluble guanylyl cyclase, LAE left atrial enlargement, CO cardiac output, PCWP pulmonary capillary wedge pressure, SGLT-2 sodium glucose cotransporter-2, HF heart failure, PAP pulmonary artery pressure, LVH left ventricular hypertrophy, PDE-5 phosphodiesterase-5, MRA mineralocorticoid receptor antagonist, ECV extracellular volume fraction, MRI magnetic resonance imaging, E/e′ mitral early diastolic velocity/mitral annular velocity, LVMI left ventricular mass index, IASD interatrial shunt device, ASV adaptive servo-ventilation, HFrEF heart failure with reduced ejection fraction, AHI apnea–hypopnea index