Assessment of Cardiac Energy Metabolism, Function and Physiology in Patients With Heart Failure Taking Empagliflozin - EMPA-VISION

Aug 21, 2023
Font Size
A
A
A
Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Kim A. Eagle, MD, MACC
Trial Sponsor:
Boehringer Ingelheim
Date Published:
04/18/2023
Date Updated:
08/21/2023
Original Posted Date:
08/21/2023
References

Contribution To Literature:

The EMPA-VISION trial showed that empagliflozin 10 mg daily does not have salutary effects on myocardial energetics or substrate metabolism compared with placebo in patients with either HFrEF or HFpEF.

Description:

The goal of the trial was to assess the impact of empagliflozin on cardiac energetics and physiology.

Study Design

Eligible patients were randomized in a 1:1 fashion to either empagliflozin 10 mg daily (n = 35) or placebo (n = 37). There were two separate cohorts with heart failure with reduced ejection fraction (HFrEF: left ventricular ejection fraction [LVEF] ≤40%) and heart failure with preserved ejection fraction (HFpEF: LVEF ≥50%).

  • Total screened: 101
  • Total number of enrollees: 72
  • Duration of follow-up: 12 weeks
  • Mean patient age: 68 years
  • Percentage female: 42%

Inclusion criteria:

  • An established diagnosis of nonischemic, chronic HF with typical signs (N-terminal pro-B-type natriuretic peptide >125 pg/mL in sinus rhythm or >600 pg/mL in atrial fibrillation) and symptoms (New York Heart Association [NYHA] classes II–IV) and appropriate doses of guideline-directed HF medical therapy
  • In addition, patients with HFpEF were required to display significant signs of adverse structural remodeling (left atrial volume index >34 mL/m2; left ventricular mass index >95 g/m2 [women] and >115 g/m2 [men])

Exclusion criteria:

  • Significant coronary artery disease
  • Ischemia
  • Implanted devices
  • Recent (within 1 week before screening visit) decompensated HF
  • Severely impaired renal function (creatinine clearance <30 mL/min by Cockcroft–Gault formula)

Other salient features/characteristics:

  • White race: 97%
  • Mean estimated glomerular filtration rate: 70
  • NYHA class II: 80%
  • Diabetes: 12%

Principal Findings:

The primary outcome, difference between empagliflozin and placebo for change in the resting cardiac phosphocreatine:ATP ratio (PCr/ATP) between baseline and week 12 based on cardiovascular magnetic resonance (CMR) (HFrEF cohort): -0.25 (95% confidence interval [CI] -0.58 to 0.09), p = 0.14.

Difference between empagliflozin and placebo for change in the resting PCr/ATP between baseline and week 12 (HFpEF cohort) based on CMR: -0.16 (95% CI -0.60 to 0.29), p = 0.47.

Secondary outcomes:

  • Difference between empagliflozin and placebo for change in the PCr/ATP ratio of dobutamine stress between baseline and week 12 based on CMR (HFrEF cohort): -0.13 (-0.35 to 0.09), p = 0.23
  • Difference between empagliflozin and placebo for change in the PCr/ATP ratio of dobutamine stress between baseline and week 12 based on CMR (HFpEF cohort): -0.22 (-0.66 to 0.23), p = 0.32
  • Difference between empagliflozin and placebo for change in LV mass between baseline and 12 weeks (HFrEF cohort): -9.65 (-17.5 to -1.8): p < 0.05
  • Difference between empagliflozin and placebo for change in LV mass between baseline and 12 weeks (HFpEF cohort): -0.41 (-10.86 to 10.04): p = 0.94
  • Difference between empagliflozin and placebo for change in peak oxygen consumption between baseline and 12 weeks (HFrEF cohort): 0.69 (-1.25 to 2.63): p = 0.47
  • Difference between empagliflozin and placebo in change in peak oxygen consumption between baseline and 12 weeks (HFpEF cohort): 0.08 (-2.14 to 2.31): p = 0.98

Interpretation:

The results of this small mechanistic trial indicate that empagliflozin 10 mg daily does not have salutary effects on myocardial energetics or substrate metabolism compared with placebo in patients with either HFrEF or HFpEF.

References:

Hundertmark MJ, Adler A, Antoniades C, et al. Assessment of Cardiac Energy Metabolism, Function, and Physiology in Patients With Heart Failure Taking Empagliflozin: The Randomized, Controlled EMPA-VISION Trial. Circulation 2023;147:1654-69.

Clinical Topics: Arrhythmias and Clinical EP, Diabetes and Cardiometabolic Disease, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Echocardiography/Ultrasound, Magnetic Resonance Imaging

Keywords: Arrhythmia, Sinus, Atrial Fibrillation, Diagnostic Imaging, Dobutamine, Echocardiography, Stress, Heart Failure, Magnetic Resonance Imaging, Metabolic Syndrome, Metabolism, Natriuretic Peptide, Brain, Physiology, Stroke Volume


< Back to Listings