Ischemia With Nonobstructive Coronary Arteries

Reynolds, Harmony R.; Díaz, Ariel; Cyr, Derek D.; Shaw, Leslee J.; Mancini, G.B. John; Leipsic, Jonathon; Budoff, Matthew J.; Min, James K.; Hague, Cameron; Berman, Daniel S.; Chaitman, Bernard R.; Picard, Michael H.; Hayes, Sean W.; Scherrer‐Crosbie, Marielle; Kwong, Raymond Y.; Lópes, Renato D.; Senior, Roxy; Dwivedi, Sudhanshu Kumar; Miller, Todd D.; Chow, Benjamin J.W.; Silva, Ramesh de; Stone, Gregg W.; Boden, William E.; Bangalore, Sripal; O’Brien, Sean M.; Hochman, Judith S.; Maron, David J.

doi:10.1016/j.jcmg.2022.06.015

Cited by 40 publications

(20 citation statements)

References 42 publications

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“…This might be due to the patchy distribution pattern of microvascular ischemia, which can also affect “remote” myocardium. Consistent with our findings, a recent subanalysis of the ISCHEMIA trial also found that patients with INOCA tended to have lower degrees of ischemia on noninvasive stress testing compared with obstructive CAD 27 . This might explain why relative CTP-MBF seems to be close to reach statistical significance in contrast to absolute CTP-MBF in our study.…”

Section: Discussionsupporting

confidence: 91%

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Differentiating Macrovascular and Microvascular Ischemia Using Fractal Analysis of Dynamic Myocardial Perfusion Stress-CT

Michallek,

Nakamura,

Kurita

et al. 2023

Invest Radiol

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Objectives Fractal analysis of dynamic myocardial stress computed tomography perfusion imaging (4D-CTP) has shown potential to noninvasively differentiate obstructive coronary artery disease (CAD) and coronary microvascular disease (CMD). This study validates fractal analysis of 4D-CTP in a multicenter setting and assesses its diagnostic accuracy in subgroups with ischemia and nonobstructed coronary arteries (INOCA) and with mild to moderate stenosis. Materials and Methods From the AMPLIFiED multicenter trial, patients with suspected or known chronic myocardial ischemia and an indication for invasive coronary angiography were included. Patients underwent dual-source CT angiography, 4D-CTP, and CT delayed-enhancement imaging. Coronary artery disease, CMD, and normal perfusion were defined by a combined reference standard comprising invasive coronary angiography with fractional flow reserve, and absolute or relative CT-derived myocardial blood flow. Nonobstructed coronary arteries were defined as ≤25% stenosis and mild to moderate stenosis as 26%–80%. Results In 127 patients (27% female), fractal analysis accurately differentiated CAD (n = 61, 23% female), CMD (n = 23, 30% female), and normal perfusion (n = 34, 35% female) with a multiclass area under the receiver operating characteristic curve (AUC) of 0.92 and high agreement (multiclass κ = 0.89). In patients with ischemia (n = 84), fractal analysis detected CAD (n = 61) over CMD (n = 23) with sensitivity of 95%, specificity of 74%, accuracy of 89%, and AUC of 0.83. In patients with nonobstructed coronary arteries (n = 33), INOCA (n = 15) was detected with sensitivity of 100%, specificity of 78%, accuracy of 88%, and AUC of 0.94. In patients with mild to moderate stenosis (n = 27), fractal analysis detected CAD (n = 19) over CMD with sensitivity of 84%, specificity of 100%, accuracy of 89%, and AUC of 0.95. Conclusions In this multicenter study, fractal analysis of 4D-CTP accurately differentiated CAD and CMD including subgroups with INOCA and with mild to moderate stenosis.

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Section: Discussionsupporting

confidence: 91%

“…A smaller cohort with INOCA has been identified in the ISCHEMIA population (n = 476, 13%) and comprehensively characterized: INOCA was more common in younger women and included all degrees of ischemia 27 . Furthermore, microvascular ischemia has been associated with MACE, especially in women 28,29 .…”

Section: Discussionmentioning

confidence: 99%

Differentiating Macrovascular and Microvascular Ischemia Using Fractal Analysis of Dynamic Myocardial Perfusion Stress-CT

Michallek,

Nakamura,

Kurita

et al. 2023

Invest Radiol

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“…Men are more likely to suffer from intraplaque haemorrhage secondary to neovessel-rupture, whereas women more often present with coronary microvascular dysfunction (CMD) and subsequent angina with non-obstructive coronary arteries. [56][57][58] This is noteworthy, considering that female hormone signalling has been associated with CMD, 59 while oestrogen replacement therapy has not been found effective to halt classical obstructive atherosclerotic plaque progression in post-menopausal women with ischaemic heart disease. 60,61 The findings of our present study further substantiate the concept that in the development of CAD, both sexes exhibit numerous common risk factors in addition to sex-specific mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Sex-Specific Associations of the Plasma-Proteome with incident Coronary Artery Disease

Sier,

Willems van Dijk,

van Heemst

et al. 2024

Preprint

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Background and Aims The aetiology of coronary artery disease (CAD) is different for men and women, yet insights into underlying sex-specific biological and pathophysiological mechanisms are limited. We investigated the sex-specific associations of the plasma-proteome with incident CAD. Methods In 40,829 participants from UK Biobank free-of-CAD from baseline to 365 days thereafter (55% women, mean 56.9, standard deviation 8.1 years), we analysed associations between 2,922 plasma-proteins and CAD incidence. Baseline plasma samples (2006-2010), were analysed in relation to incident CAD over a median follow-up of 13.7 (IQR: 13.1,14.4) years. Combined and sex-specific analyses were performed using Cox-proportional hazard models, adjusting for considered confounders, and causal inference using Mendelian Randomisation (MR). Results Multivariable-adjusted Cox-proportional hazard models identified 1,138 proteins associated with incident CAD (false-discovery-rate-corrected p-value<0.05), of which 219 showed evidence for potential causality using MR. Overrepresentation analyses identified involvement of cytokine-cytokine receptor interactions (p<0.0001), matrix remodelling (p<0.0001), regulation of innate and adaptive immune cells (p<0.0001), and angiogenesis (p<0.0001) pathways associated with incident CAD. Sex-specific analyses revealed additional 412 female-exclusive and 37 male-exclusive proteins and distinct CAD-risk pathways were identified for women (e.g., innate immune response) and men (e.g., tube morphogenesis (angiogenesis)). Translation toward druggability on targets with causal evidence revealed sex-specific clinical drug candidates such as C1S (men) and FOXO1 (women). Conclusions Although the majority of proteins showed consistent associations with incident CAD in both sexes, multiple proteins and biological pathways were either more strongly associated with incident CAD in men or in women, potentially indicating sex-specific pathogenesis and opening new alleys for prevention and clinical strategies.

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“… 1 More recently, a post hoc analysis of the ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) trial reported that 13% of patients were without obstructive coronary artery disease even though these patients had evidence of moderate to severe ischemia according to noninvasive tests. 10 These patients often suffer from repeated chest pain that causes hospital readmission for invasive tests, leading to increased medical burden and cost. It is reported that about 50% of patients with nonobstructive coronary arteries experienced recurrent chest pain and impairment in functional capacity and quality of life.…”

Section: Clinical Importance Of Inocamentioning

confidence: 99%