Diabetes Mellitus, Heart Failure, Diastolic, Heart Failure with Preserved Ejection Fraction
Conditions
Keywords
Exercise, Invasive Exercise Testing, SGLT-2 Inhibitors
Brief summary
Sodium-Glucose Cotransporter-2 (SGLT-2) inhibitors generally and empagliflozin specifically have shown cardiovascular benefits in patients with heart failure (HF), but the underlying mechanisms remain unclear. Empagliflozin use resulted in lower pulmonary artery diastolic pressures in patients with HF, suggesting a beneficial diuretic effect. Other potential mechanisms include increased blood volume, decreased blood pressure, and changes in sympathetic and neuro-hormonal activation. This study is a single-arm, open label, prospective interventional study of 8 subjects with heart failure with preserved ejection fraction (HFpEF). Before and after 12 weeks of daily empagliflozin, participants with undergo comprehensive invasive exercise testing with a right heart catheter. Our goal is to evaluate the effects of empagliflozin on fitness, assessed by peak VO2, and peak left ventricular filling pressure, assessed by pulmonary capillary pressure at peak exercise.
Detailed description
This is a single-arm, open label, pilot study of 8 subjects with HFpEF. The subjects will undergo screening tests (exercise stress echo and blood work) to evaluate for potential exclusion criteria and provide familiarization to the exercise protocol. Those included will undergo an echocardiogram and invasive cardiopulmonary exercise test. This involves placement of a right heart catheter in the pulmonary artery and undergoing seated, upright exercise. During the exercise test, the subject's oxygen uptake (VO2), intra-cardiac pressures (right atrial pressure, pulmonary capillary wedge pressure) and cardiac output (Qc) will be measured. The subject will take a dose of empagliflozin in the lab and wait for at least 60 minutes. They will repeat a shortened version of the exercise test in the afternoon. After baseline testing, each subject will take 10mg empagliflozin daily for 12 weeks. They will have repeat blood work (specific electrolytes and renal function) 30 days after starting medication to screen for renal injury. After 12 weeks, they will return for another invasive cardiopulmonary exercise test and echocardiogram.
Interventions
DRUGEmpagliflozin 10 MG
Daily Empagliflozin
Sponsors
Boehringer Ingelheim
University of Texas Southwestern Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single arm, open label trial
Eligibility
Sex/Gender
ALL
Age
50 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* adults ages 50-85 * clinical heart failure * ejection fraction \> 50%
Exclusion criteria
* previous hypersensitivity or adverse reaction to SGLT-2 inhibitors * currently treated with SGLT-2 inhibitor * current or prior ejection fraction \<50% * chronic kidney disease with glomerular filtration rate \< 45 ml/kg/min * unstable coronary artery disease * significant arrhythmia * BMI \>55 kg/m2 * inability to exercise.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peak Oxygen Uptake | 12 weeks | Peak VO2 measured on maximal exercise test |
| Peak Pulmonary Capillary Wedge Pressure (PCWP) | 12 weeks | Peak PCWP, measured at end-expiration, at the end of maximal exercise test |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Stroke Volume at Rest and During Exercise | 12 weeks | — |
| Right Atrial Pressure at Rest and During Exercise | 12 weeks | — |
| Pulmonary Capillary Wedge Pressure at Rest and During Submaximal Exercise | 12 weeks | — |
| Primary Endpoints after single dose of empagliflozin | 1 hour | Peak VO2 and peak PCWP will be measured after a single dose of empagliflozin |
| Hemoglobin mass, plasma volume, total blood volume | 12 weeks | Measured by Carbon Monoxide Rebreathe |
| Diastolic parameters at rest and during submaximal exercise | 12 weeks | Measured by echocardiography |
| 6 minute walk time | 12 weeks | — |
| Left ventricular volumes at rest and during submaximal exercise | 12 weeks | Measured by echocardiography |
| Cardiac Output at Rest and During Exercise | 12 weeks | — |
Countries
United States
Outcome results
None listed