(CCSP080) TACKLING CORONARY MICROVASCULAR DYSFUNCTION IN HEART FAILURE WITH MILDLY REDUCED OR PRESERVED EJECTION FRACTION

Background: Despite representing 50% of the heart failure (HF) population, clinical outcomes and quality of life of individuals with heart failure with mildly reduced (HFmrEF) or preserved (HFpEF) ejection fraction remain poor. Inflammation is central to the pathophysiological process of HF in many of these patients and is mainly driven by their numerous comorbidities. Many mechanisms have been postulated for this inflammatory milieu, amongst which myocardial damage due to coronary microvascular dysfunction (CMD) seems fundamental, reinforcing the importance of targeting inflammation as a potential treatment for patients with HFmrEF or HFpEF. Colchicine is an anti-inflammatory agent that has recently shown benefits in patients with coronary artery disease. In patients with HFmrEF or HFpEF, colchicine may improve CMD and circulating biomarkers of inflammation and fibrosis.

METHODS AND RESULTS: In a single-center, randomized, double-blinded, placebo-controlled study, we aim to evaluate the effects of colchicine on CMD in patients with either HFmrEF or HFpEF and inflammation. We will enroll 80 participants with HF and left ventricular ejection fraction > 40% and elevated high-sensitivity C-reactive protein levels (hs-CRP, ≥2 mg/L). Patients will be randomly assigned in a 1:1 ratio to receive a 6-month course of colchicine at a dose of 0.5 mg twice daily or placebo. We will compare the change between baseline and six months in coronary flow reserve, a marker of CMD, assessed using adenosine-based positron emission tomography imaging. In addition, a broad set of circulating inflammation (including MPO, IL-1b, IL-6, TNF-a, sICAM-1) and myocardial fibrosis (including sST2, MMP-2/-9) biomarkers will be measured at baseline and six months using Olink Multiplex cardiovascular and inflammation panels (Olink, Uppsala, Sweden), a high-throughput multiplex immunoassay.

Conclusion: HFmrEF and HFpEF can be considered systemic inflammatory states induced by their frequent associated co-morbidities. While inflammation seems central to disease development and progression, whether a potent anti-inflammatory agent such as colchicine may improve CMD related to inflammation and circulating biomarkers of myocardial fibrosis is unknown. This mechanistic study aims to validate the role of inflammation as a potentially modifiable promoter of myocardial damage associated with CMD in patients with HFmrEF or HFpEF.