Does coronary microvascular dysfunction play a role in heart failure with reduced ejection fraction?

Area of Science:

• Cardiovascular Research
• Heart Failure Pathophysiology
• Pharmacology

Background:

• Current heart failure (HF) therapies primarily slow disease progression.
• A potential strategy involves targeting the causal mechanisms of HF for reversal.
• Insufficient myocardial blood flow (MBF) leading to ischemia is hypothesized as a key cause of HF.

Purpose of the Study:

• To investigate the relationship between MBF and cardiac work (WSRP) in a mouse model of HF.
• To evaluate the therapeutic potential of the coronary vasodilator chromonar in reversing HF.
• To determine if targeting MBF can halt or reverse HF progression.

Main Methods:

• Measured MBF and WSRP during norepinephrine infusion in control mice, HF mice (TAC-HF), and chromonar-treated HF mice (TAC-Chromonar).
• Assessed cardiac function, including ejection fraction.
• Utilized cardiac hypoxia fate-mapping and capillary density analysis.

Main Results:

• In TAC-HF mice, MBF failed to increase with increased cardiac work, unlike in controls.
• Chromonar treatment restored the relationship between MBF and cardiac work in HF mice.
• Chromonar reversed the decline in ejection fraction and reduced cardiac myocyte hypoxia and capillary rarefaction.

Conclusions:

• Inadequate MBF to meet the metabolic demands of the working heart is a significant cause of HF.
• Pharmacological coronary vasodilation with chromonar can increase MBF in HF.
• Chromonar treatment demonstrated potential to reverse functional decline and improve cardiac function in HF.