Coronary microvascular function and myocardial fibrosis in women with angina pectoris and no obstructive coronary artery disease: the iPOWER study

Introduction: Coronary microvascular dysfunction (CMD) is prevalent in symptomatic patients with no obstructive coronary artery disease. We postulated that exercise capacity and cardiac output augmentation in response to exercise are linked to coronary microvascular function in this patient population. Methods: Fifty-one consecutive patients with unexplained cardiac exertion symptoms, non-obstructive coronary artery disease on angiography (<50% stenosis), and normal left ventricular ejection fraction (>50%) who underwent concurrent clinically indicated coronary reactivity testing and invasive cardiopulmonary exercise testing (CPEX) were included. Microvascular function was assessed by coronary flow reserve (CFR; hyperemic/resting flow) in response to intracoronary adenosine injection. Cardiac output (CO) was calculated at rest and peak exercise using Fick’s formula. CO limitation was defined as a measured (peak CO - resting CO) <80% than the expected [6*absolute ΔVO 2 (Peak VO 2 -Rest VO 2 ) increase in CO in L/min]. The relationship between CFR, maximal exercise capacity, and CO augmentation at peak exercise was explored. Results: Patients were 56.6±10.5 years old and 73% were females. CFR had a modest positive correlation with measured increase in CO (r=0.42; P=0.003) ( Fig 1A ), and with maximal ergometric exercise capacity [in Watts/Kg] (Pearson’s r=0.33, P=0.02) ( Fig 1B ). Patients with, vs. without impaired cardiac limitations during exercise, had significantly lower CFR levels (2.6±0.5 vs 3.1±0.7; P=0.01) ( Fig 2 ). Conclusion: Impaired coronary microvascular function is associated with lower peak exercise capacity and reduced cardiac output augmentation in response to exercise, underscoring the functional ramification of CMD in symptomatic patients.

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Biomarkers of Myocardial Fibrosis are Associated with Diabetes but not with Coronary Microvascular Dysfunction in Women with Angina and No Obstructive Coronary Artery Disease

10.21203/rs.3.rs-36838/v1 ◽

2020 ◽

Author(s):

Kira Bang Bove ◽

Naja Dam Mygind ◽

Signe Holm Nielsen ◽

Marie Mide Michelsen ◽

Daria Frestad Bechsgaard ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Angina Pectoris ◽

Myocardial Fibrosis ◽

Obstructive Coronary Artery Disease ◽

Microvascular Dysfunction ◽

Coronary Microvascular Dysfunction ◽

Transthoracic Doppler Echocardiography ◽

Type Iv ◽

Artery Disease

Abstract Background Coronary microvascular dysfunction (CMD) is highly prevalent in women with no obstructive coronary artery disease and possibly related to myocardial fibrosis caused by excessive extracellular matrix (ECM) remodeling. ECM turnover can be measured in blood indicating fibrotic activity. We hypothesized that women with DM, angina and no obstructive coronary artery disease have increased ECM turnover and that this is associated with CMD.Methods We included 344 women with angina pectoris and no obstructive coronary artery disease (187 with DM, predominantly type II) and 76 asymptomatic women without DM as controls. Biomarkers reflecting formation of type IV and VI collagen (PRO-C4 and PRO-C6) and degradation of type IV, V and VI collagen (C4M, C5M, C6M), mimecan (MIM) and titin (TIM) were measured in all participants. CMD was defined as coronary flow velocity reserve (CFVR) <2.0 assessed by transthoracic Doppler echocardiography.Results Median age was 64.2 (IQR 57.0-70.0), slightly higher in symptomatic women with DM. Median CFVR was 2.21 (1.89-2.55) in symptomatic women with DM, 2.35 (1.96-2.77) in symptomatic women without DM and 2.63 (2.19-2.95) in controls (age-adjusted p for trend<0.001). With exception of CM5, women with DM had significantly higher levels of all ECM biomarkers than women without DM (age-adjusted p<0.01), whereas biomarkers did not differ between symptomatic women without DM and controls. High ECM biomarker levels were associated with HbA1c, high BMI, low HDL and high triglycerides (p=0.003-0.0001). There was no correlation between ECM biomarkers and CFVR.Conclusion Women with angina pectoris and DM had increased levels of myocardial fibrosis biomarkers compared with women without DM. There was no association between CMD and biomarkers of myocardial fibrosis.

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Design and rationale of the EVOCATION trial: A prospective, randomized, exploratory study comparing the effect of evolocumab on coronary microvascular function after percutaneous coronary intervention in patients with stable coronary artery disease

Journal of Cardiology ◽

10.1016/j.jjcc.2021.08.024 ◽

2021 ◽

Author(s):

Masanori Asakura ◽

Kiyoshi Hibi ◽

Wataru Shimizu ◽

Kenshi Fujii ◽

Satoru Suwa ◽

...

Keyword(s):

Coronary Artery Disease ◽

Percutaneous Coronary Intervention ◽

Coronary Artery ◽

Exploratory Study ◽

Stable Coronary Artery Disease ◽

Coronary Intervention ◽

Microvascular Function ◽

Percutaneous Coronary ◽

Artery Disease ◽

Coronary Microvascular Function

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Accelerated collagen turnover in women with angina pectoris without obstructive coronary artery disease: An iPOWER substudy

European Journal of Preventive Cardiology ◽

10.1177/2047487318758750 ◽

2018 ◽

Vol 25 (7) ◽

pp. 719-727 ◽

Cited By ~ 7

Author(s):

Signe H Nielsen ◽

Naja D Mygind ◽

Marie M Michelsen ◽

Daria F Bechsgaard ◽

Hannah E Suhrs ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Angina Pectoris ◽

Myocardial Fibrosis ◽

Volume Fraction ◽

Extracellular Volume ◽

Diffuse Myocardial Fibrosis ◽

Collagen Turnover ◽

Collagen Formation ◽

Artery Disease

Aim Collagens are major cardiac extracellular matrix components, known to be actively remodelled and accumulated during diffuse myocardial fibrosis. We evaluated whether accelerated collagen turnover described by neo-epitope biomarkers reflecting collagen formation and degradation separates patients with diffuse myocardial fibrosis from asymptomatic controls. Methods and results Seventy-one women with angina pectoris without significant coronary artery disease assessed by invasive coronary angiogram were included. Competitive enzyme-linked immunosorbent assays (ELISAs) measuring circulating protein fragments in serum assessed the formation and degradation of collagen type III (Pro-C3, C3M and C3C), IV (P4NP7S and C4M), V (Pro-C5 and C5M) and VI (Pro-C6 and C6M), and degradation of collagen type I (C1M). Serum samples from 32 age-matched asymptomatic women were included as controls. Symptomatic women presented significantly elevated levels of Pro-C6, C3C, C3M, C4M and C8-C ( p < 0.0001–0.0058) and significantly decreased levels of Pro-C3, C5M and C6M ( p < 0.0001–0.041), reflecting accelerated collagen turnover and an imbalanced collagen formation and degradation compared to controls. Cardiac magnetic resonance T1 mapping was performed to determine extracellular volume fraction and thus diffuse myocardial fibrosis. A significant association was identified between C5M and extracellular volume fraction by cardiac magnetic resonance ( p = 0.01). Conclusion Women with angina pectoris, but without significant obstructive coronary artery disease, showed an imbalanced collagen turnover compared to asymptomatic controls. The examined biomarkers are tools to monitor active collagen remodelling in patients with angina pectoris, in risk of developing myocardial fibrosis.

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