May 16, 2009Circulation Cardiovascular GeneticsOpen Access

Cardiac Resynchronization Therapy Corrects Dyssynchrony-Induced Regional Gene Expression Changes on a Genomic Level

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Key result

Cardiac resynchronization therapy reversed dyssynchrony-induced changes in 1050 gene transcripts to levels of nonpaced hearts, significantly reducing regional expression heterogeneity.

Why the study?

Does biventricular pacing correct dyssynchrony-induced regional gene expression changes in a canine model of heart failure?

Structured PICO

Does biventricular pacing correct dyssynchrony-induced regional gene expression changes in a canine model of heart failure?

Population

Adult male mongrel dogs with tachypacing-induced dyssynchronous heart failure (left bundle branch radiofrequency ablation and right atrial pacing at 200 bpm)

Intervention

Biventricular tachypacing (cardiac resynchronization therapy) for 3 weeks

Comparator

Continued right atrial tachypacing (dyssynchronous heart failure) for 6 weeks, and non-paced control animals without left bundle branch block

Outcome

Regional alterations in the myocardial transcriptome (gene expression changes in anterior vs lateral left ventricular walls)surrogate

Cardiac resynchronization therapy corrects dyssynchrony-induced regional gene expression changes in the anterior left ventricular wall, demonstrating a global transcriptomic effect of biventricular pacing.

Limitations

Tachypacing-induced HF does not mimic all features of human HF (dissimilar to clinical forms caused by chronic ischemia or hypertensive disease)
Pharmacological interventions known to disrupt neurohormonal dysfunction in HF (e.g., beta-blockers or ACE inhibitors) were not used
Tachypacing was maintained throughout the study, which might delay benefits from resynchronization
Higher heart rate necessary to induce and maintain HF may cause remodeling processes to differ from clinical HF syndrome

Discussion

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Implication

Provides mechanistic insight from canine dyssynchrony; leaves open human translation and clinical relevance.

Cite This Study

Barth et al. (2009) studied this question. Cardiac resynchronization therapy reversed dyssynchrony-induced changes in 1050 gene transcripts to levels of nonpaced hearts, significantly reducing regional expression heterogeneity.

synapsesocial.com/papers/6970eb032d1b404414ca79ba https://doi.org/10.1161/circgenetics.108.832345

Topics

Heart failure HFrEF treatment

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Cardiac Resynchronization Therapy Corrects Dyssynchrony-Induced Regional Gene Expression Changes on a Genomic Level

Structured PICO

Limitations

Discussion

Implication

Cite This Study

Topics

Cardiac Resynchronization Therapy Corrects Dyssynchrony-Induced Regional Gene Expression Changes on a Genomic Level

Structured PICO

Limitations

Discussion

Implication

Cite This Study

Also Consider

Topics

Also Consider