April 23, 2026European Heart Journal39 citationsOpen Access
View Full PaperAcyl ghrelin improves cardiac function in heart failure and increases fractional shortening in cardiomyocytes without calcium mobilization
Key Result
Intravenous acyl ghrelin increased cardiac output by 28% compared to placebo in patients with heart failure and reduced ejection fraction, without causing adverse hemodynamic events.
Key Points
- This research aims to evaluate the cardiovascular effects of acyl ghrelin in heart failure patients and isolated cardiomyocytes.
- Randomized placebo-controlled double-blind trial with 31 patients with chronic heart failure
- Synthetic human acyl ghrelin (0.1 µg/kg/min) administered intravenously for 120 min
- Ex vivo assessment of cardiomyocytes for fractional shortening and calcium transients
- Acyl ghrelin increased cardiac output significantly from 4.08 ± 1.15 to 5.23 ± 1.98 L/min, P < 0.001
- In cardiomyocytes, acyl ghrelin increased fractional shortening but did not change calcium transients
- No adverse effects on blood pressure or arrhythmias were observed.
Study Design
Type
RCT (n=30)
Blinding
Double-blind
Randomization
1:1 block randomization
Multicenter
No
Structured PICO
Does intravenous acyl ghrelin improve cardiac output in patients with chronic HFrEF?
P
Population
31 patients with chronic heart failure with reduced ejection fraction (HFrEF) and isolated mouse cardiomyocytes
I
Intervention
Synthetic human acyl ghrelin (0.1 µg/kg/min) intravenously over 120 min
C
Comparator
Placebo intravenously over 120 min
O
Outcome
Change in cardiac output (CO)surrogate
Intravenous acyl ghrelin acutely improves cardiac output and stroke volume in patients with HFrEF without causing adverse hemodynamic or ischemic effects, likely via calcium-independent increases in contractility.
Main Result
Absolute Event Rate: 5.23% vs 4.11%
p-value: p=<0.001
Limitations
- Single center study
- Small sample size
- Short-term infusion duration (120 minutes) limits assessment of long-term clinical outcomes
Abstract
BACKGROUND AND AIMS: Ghrelin is an endogenous appetite-stimulating peptide hormone with potential cardiovascular benefits. Effects of acylated (activated) ghrelin were assessed in patients with heart failure and reduced ejection fraction (HFrEF) and in ex vivo mouse cardiomyocytes. METHODS AND RESULTS: In a randomized placebo-controlled double-blind trial, 31 patients with chronic HFrEF were randomized to synthetic human acyl ghrelin (0.1 µg/kg/min) or placebo intravenously over 120 min. The primary outcome was change in cardiac output (CO). Isolated mouse cardiomyocytes were treated with acyl ghrelin and fractional shortening and calcium transients were assessed. Acyl ghrelin but not placebo increased cardiac output (acyl ghrelin: 4.08 ± 1.15 to 5.23 ± 1.98 L/min; placebo: 4.26 ± 1.23 to 4.11 ± 1.99 L/min, P < 0.001). Acyl ghrelin caused a significant increase in stroke volume and nominal increases in left ventricular ejection fraction and segmental longitudinal strain and tricuspid annular plane systolic excursion. There were no effects on blood pressure, arrhythmias, or ischaemia. Heart rate decreased nominally (acyl ghrelin: 71 ± 11 to 67 ± 11 b.p.m.; placebo 69 ± 8 to 68 ± 10 b.p.m.). In cardiomyocytes, acyl ghrelin increased fractional shortening, did not affect cellular Ca2+ transients, and reduced troponin I phosphorylation. The increase in fractional shortening and reduction in troponin I phosphorylation was blocked by the acyl ghrelin antagonist D-Lys 3. CONCLUSION: In patients with HFrEF, acyl ghrelin increased cardiac output without causing hypotension, tachycardia, arrhythmia, or ischaemia. In isolated cardiomyocytes, acyl ghrelin increased contractility independently of preload and afterload and without Ca2+ mobilization, which may explain the lack of clinical side effects. Ghrelin treatment should be explored in additional randomized trials. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05277415.