September 12, 2026Circulation Heart Failure0 citations
Cardiac Resynchronization Therapy and Circulating Metabolomic Profile in Patients With Advanced Heart Failure
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Key Result
Cardiac resynchronization therapy improved LVEF from 28.9% at baseline to 40.1% at 12 months (P<0.001) and modulated systemic plasma metabolomic profiles, including reduced ketone bodies.
Key Points
- To evaluate the impact of cardiac resynchronization therapy on left ventricular ejection fraction and circulating plasma metabolites in patients with advanced heart failure with reduced ejection fraction.
- Prospective observational cohort of 92 patients with ischemic or nonischemic cardiomyopathy receiving a cardiac resynchronization therapy defibrillator for LVEF ≤35%.
- Performed echocardiography and plasma metabolomic profiling using gas chromatography-mass spectrometry and 1H nuclear magnetic resonance spectroscopy before CRT and at 6 months post-implantation.
- LVEF improved significantly from 28.9±7.6% at baseline to 36.0±11.3% at 6 months (P <0.001) and to 40.1±12.6% at 12 months (P <0.001).
- Post-CRT plasma showed significant reductions in 42 metabolite features, notably ketone bodies including 3-hydroxybutyrate (P <0.001) and acetone (P = 0.01), as well as the branched-chain amino acid isoleucine (P = 0.01).
- Metabolite reductions predominated in nonischemic cardiomyopathy, whereas ischemic cardiomyopathy exhibited enhanced amino acid oxidation and elevated lactate and pyruvate.
Study Design
Type
Cohort (n=92)
Structured PICO
Does cardiac resynchronization therapy improve systemic metabolomic profile and left ventricular function in patients with advanced heart failure?
P
Population
92 patients (mean age 67.3 years, 37.0% female) with ischemic or nonischemic cardiomyopathy and LVEF ≤35% receiving cardiac resynchronization therapy, followed for 12 months.
E
Exposure
Cardiac resynchronization therapy (CRT) with a defibrillator
O
Outcome
Left ventricular ejection fraction (LVEF) and circulating plasma metabolites at 6-month follow-upsurrogate
Cardiac resynchronization therapy improves left ventricular function and modulates systemic plasma metabolomic profiles, particularly reducing ketone bodies and branched-chain amino acids in nonischemic cardiomyopathy.
Main Result
Absolute Event Rate: 40.1% vs 28.9%
p-value: p=<0.001
Abstract
BACKGROUND: It is unknown whether cardiac resynchronization therapy (CRT) improves systemic metabolomic profile by enhancing left ventricular function. The observational cohort study aimed to investigate the effect of CRT on left ventricular ejection fraction (LVEF) and circulating plasma metabolites in patients who had heart failure with reduced LVEF. METHODS: We prospectively screened patients with ischemic cardiomyopathy and nonischemic cardiomyopathy who received CRT with a defibrillator for LVEF ≤35% according to current guidelines. Clinical assessment included echocardiography and device interrogation. Blood samples for metabolomic analysis were collected before CRT and at 6-month follow-up. Plasma was subjected to gas chromatography-mass spectrometry and 1 H nuclear magnetic resonance-based metabolomic analysis. RESULTS: Totally 92 patients were enrolled, with a mean age of 67.3±11.3 years (37.0% female). LVEF was significantly improved from 28.9±7.6% at baseline to 36.0±11.3% at 6 months ( P <0.001) and to 40.1±12.6% at 12 months ( P <0.001). After CRT, 42 metabolite features were significantly decreased compared with the baseline. The ketone bodies, including 3-hydroxybutyrate ( P <0.001) and acetone ( P =0.01), were reduced. A branched-chain amino acid, isoleucine, was also decreased after CRT ( P =0.01). These metabolomic changes were mainly observed in the nonischemic cardiomyopathy group, while the metabolomic profile in the ischemic cardiomyopathy group was characterized by enhanced amino acid oxidation and elevated levels of lactate and pyruvate. The improvement in LVEF positively correlated with the ratio of changes in ketone bodies and isoleucine. CONCLUSIONS: CRT may modulate the systemic plasma metabolomic profile, which correlated with improvement in left ventricular function in patients with severe heart failure with reduced ejection fraction.
Cite This Study
Qian et al. (2026) conducted a cohort in Heart failure with reduced LVEF (n=92). Cardiac resynchronization therapy (CRT) vs. Baseline (pre-CRT) was evaluated on Left ventricular ejection fraction (LVEF) (p=<0.001). Cardiac resynchronization therapy improved LVEF from 28.9% at baseline to 40.1% at 12 months (P<0.001) and modulated systemic plasma metabolomic profiles, including reduced ketone bodies.