What question did this study set out to answer?

To determine whether inhibition of TNF-alpha using etanercept prevents adverse myocardial remodeling secondary to volume overload across different stages of heart failure progression.

August 7, 2009AJP Heart and Circulatory PhysiologyOpen Access

TNF-α inhibition attenuates adverse myocardial remodeling in a rat model of volume overload

Q: What is the clinical evidence from this study?

Population: Volume overload-induced heart failure (n=66). Intervention: Etanercept vs. Untreated aortocaval fistula (FIST) and sham-operated controls. Primary outcome: Unstressed left ventricular volume (V0) at 8 weeks postfistula (μl) (p=<0.05).

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Key result

Etanercept significantly attenuated adverse myocardial remodeling, including ventricular hypertrophy, dilatation, and increased compliance, at 8 weeks postfistula in a rat model of volume overload.

Why the study?

Does etanercept prevent adverse myocardial remodeling in a rat model of volume overload?

Key Points

To determine whether inhibition of TNF-alpha using etanercept prevents adverse myocardial remodeling secondary to volume overload across different stages of heart failure progression.
Eight-week-old male Sprague-Dawley rats were randomly assigned to sham-operated controls, untreated aortocaval (AV) fistulas, or etanercept-treated AV fistulas.
Etanercept was administered subcutaneously at 1 mg/kg body weight.
Outcomes were evaluated across three postfistula time points: 3 days, 3 weeks, and 8 weeks.
Etanercept prevented collagen degradation at 3 days and significantly attenuated the decrease in collagen content at 8 weeks postfistula.
Initial ventricular dilatation was not prevented at 3 weeks, but etanercept significantly attenuated subsequent ventricular hypertrophy, dilatation, and increased compliance at 8 weeks postfistula, leading to improved functional performance.
Etanercept markedly attenuated increases in cardiomyocyte length, width, and area at 8 weeks postfistula.

Structured PICO

Does etanercept prevent adverse myocardial remodeling in a rat model of volume overload?

Population

Eight-week-old male Sprague-Dawley rats with aortocaval (AV) fistula model of heart failure

Intervention

Etanercept 1 mg/kg body wt administered subcutaneously

Comparator

Sham-operated controls and untreated AV fistulas

Outcome

Myocardial remodeling (collagen degradation, ventricular hypertrophy, dilatation, compliance) at 3 days, 3 weeks, and 8 weeks postfistulasurrogate

Main Result

Absolute Event Rate: 399% vs 466%

p-value: p=<0.05

TNF-alpha inhibition with etanercept attenuates adverse myocardial remodeling and progression to heart failure in a rat model of volume overload.

Limitations

Treatment period was limited to 3 weeks in the 8-week group to avoid potential neutralizing antibodies against the human fusion protein.
Divergent effects of different TNF-α receptors on myocardial remodeling were not investigated.
TNF-α is only one of multiple factors modulating myocardial remodeling.

Discussion

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Implication

TNF-α inhibition may limit volume-overload remodeling; leaves open translation to human HF.

Cite This Study

Jobe et al. (2009) studied Volume overload-induced heart failure (n=66). Etanercept vs. Untreated aortocaval fistula (FIST) and sham-operated controls was evaluated on Unstressed left ventricular volume (V0) at 8 weeks postfistula (μl) (p=<0.05). Etanercept significantly attenuated adverse myocardial remodeling, including ventricular hypertrophy, dilatation, and increased compliance, at 8 weeks postfistula in a rat model of volume overload.

synapsesocial.com/papers/6a0efa2406ecbe83344805e8 https://doi.org/10.1152/ajpheart.00442.2009

Topics

Heart failure HFrEF treatment

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TNF-α inhibition attenuates adverse myocardial remodeling in a rat model of volume overload

Key Points

Structured PICO

Main Result

Limitations

Discussion

Implication

Cite This Study

Topics

TNF-α inhibition attenuates adverse myocardial remodeling in a rat model of volume overload

Key Points

Structured PICO

Main Result

Limitations

Discussion

Implication

Cite This Study

Also Consider

Topics

Also Consider