What is the clinical evidence from this study?

Population: Atrial fibrillation. Intervention: Dasatinib and quercetin (D+Q) vs. Vehicle. Primary outcome: Atrial fibrillation inducibility in myocardial infarction rats (p=<0.001).

What question did this study set out to answer?

The study aims to investigate the role of cellular senescence in atrial fibrillation and its association with cardiac pathology.

January 5, 2024Cardiovascular ResearchOpen Access

The role of cellular senescence in profibrillatory atrial remodelling associated with cardiac pathology

Q: What are the key findings of this study?

Senolytic therapy with dasatinib and quercetin reduced atrial fibrillation inducibility in myocardial infarction rats from 89% to 0% (P<0.001).

Q: What question did this study set out to answer?

The study aims to investigate the role of cellular senescence in atrial fibrillation and its association with cardiac pathology.

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Key result

Senolytic therapy with dasatinib and quercetin cuts AF inducibility ~100% in post-MI rats.

P<0.001

Why the study?

Cellular senescence is believed to contribute to many cardiac conditions, but its role in AF remains unknown.

Does senolytic therapy with dasatinib and quercetin reduce atrial fibrillation susceptibility in rat models of myocardial infarction?

Key Points

The study aims to investigate the role of cellular senescence in atrial fibrillation and its association with cardiac pathology.
Evaluated atrial fibrillation susceptibility in rat models of aging and myocardial infarction.
Administered senolytic therapy (dasatinib and quercetin) from the time of surgery for 28 days.
Assessed senescence markers in human atrial tissue based on age and atrial fibrillation presence.
Aged rats showed 100% atrial fibrillation inducibility versus 87.5% in young myocardial infarction rats (P ≤ 0.001).
Senolytic therapy reduced atrial fibrillation inducibility in myocardial infarction rats from 89% to 0% (P < 0.001).
Senescence markers were upregulated in older patients (≥70 years) with long-standing atrial fibrillation compared to younger controls (≤60 years).

Structured PICO

Does senolytic therapy with dasatinib and quercetin reduce atrial fibrillation susceptibility in rat models of myocardial infarction?

Population

Rat models of aging and myocardial infarction, along with human atrial tissue, evaluated for atrial fibrillation susceptibility and senescence markers.

Intervention

Senolytic combination of dasatinib and quercetin (D+Q) administered from the time of sham or MI surgery through 28 days later.

Comparator

Corresponding vehicle.

Outcome

Atrial fibrillation susceptibility (inducibility) evaluated with programmed electrical stimulation.surrogate

Main Result

Absolute Event Rate: 0% vs 89%

p-value: p=<0.001

Senolytic therapy with dasatinib and quercetin significantly reduces atrial fibrillation inducibility and atrial fibrosis in a rat model of myocardial infarction, suggesting cellular senescence plays a key role in AF pathophysiology.

Discussion

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Implication

Senolytics warrant no clinical use for post-MI AF; leaves open senescence as a therapeutic target in humans.

Cite This Study

Mehdizadeh et al. (2024) studied Atrial fibrillation. Dasatinib and quercetin (D+Q) vs. Vehicle was evaluated on Atrial fibrillation inducibility in myocardial infarction rats (p=<0.001). Senolytic therapy with dasatinib and quercetin reduced atrial fibrillation inducibility in myocardial infarction rats from 89% to 0% (P<0.001).

synapsesocial.com/papers/6a20a0c76236d09b9bcd34ff https://doi.org/10.1093/cvr/cvae003

Topics

Atrial fibrillation Persistent AF management Anticoagulation in AF AF ablation outcomes

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The role of cellular senescence in profibrillatory atrial remodelling associated with cardiac pathology

Key Points

Structured PICO

Main Result

Discussion

Implication

Cite This Study

Topics

The role of cellular senescence in profibrillatory atrial remodelling associated with cardiac pathology

Key Points

Structured PICO

Main Result

Discussion

Implication

Cite This Study

Also Consider

Topics

Also Consider