Heart failure & cardiomyopathies
Neutrophil Extracellular Traps in Myocardial Tissue Drive Cardiac Dysfunction and Adverse Outcomes in Patients With Heart Failure With Dilated Cardiomyopathy
Authors' conclusion
NETs in myocardial tissue contribute to cardiac dysfunction and adverse outcomes in patients with heart failure with DCM, potentially through mitochondrial dysfunction of cardiomyocytes.
Study context
- Population
- Patients with HF with idiopathic dilated cardiomyopathy (DCM) undergoing endomyocardial biopsy
- Participants
- 62 patients
- Comparison
- DCM with neutrophil extracellular traps (NETs) vs without NETs in myocardial tissue
- NETsn = 32
- No NETsn = 30reference
Methodological detailsconsecutive patients, endomyocardial biopsy, ex vivo and in vivo experiments
- Consecutive patients
- Endomyocardial biopsy
- Ex vivo and in vivo experiments
Main finding
As reported in the abstract
- NETs per myocardial tissue area and proportion of NETs per neutrophil significantly higher in DCM vs non-DCM controls without HF
- Number of NETs negatively correlated with LVEF
- DCM with NETs: lower LVEF and higher BNP than without NETs
- Presence of NETs independently associated with increased risk of adverse cardiac events (multivariable Cox model)
Further findings
Cardiomyocyte mitochondrial oxygen consumption (ex vivo)
- NETs-containing conditioned medium or purified NET components impaired mitochondrial oxygen consumption; abolished with PAD4 ablation in neutrophils
LVEF after transverse aortic constriction (mouse) · 4 weeks
- LVEF reduced in wild-type mice; preserved in PAD4-deficient mice without NET formation
Original publication
Neutrophil Extracellular Traps in Myocardial Tissue Drive Cardiac Dysfunction and Adverse Outcomes in Patients With Heart Failure With Dilated Cardiomyopathy. Circ Heart Fail. Published 7 June 2024. doi:10.
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