Anatomical, haemodynamic, biochemical and imaging characteristics of the coronary collateral circulation in acute and chronic atherosclerotic disease processes

Aim: Although frequently identified during coronary angiography, the mechanisms by which coronary collaterals develop, and their prognostic implications are, to date, unknown. This body of work aims to determine the prevalence and predictors of coronary collateral recruitment in the setting of ST elevation myocardial infarction (STEMI) and chronic total occlusion (CTO) and to determine their prognostic impact. Furthermore, to identify biochemical, cellular and haemodynamic processes by which collaterals are recruited and mature, and influence haemodynamics in the coronary circulation. Methods: Anatomical grading of collaterals using the Rentrop classification was performed in a large cohorts of patients with STEMI and CTO to determine predictors, reproducibility and prognostic implications of collaterals. Data linkage with other health parameters including a history of obstructive sleep apnoea (OSA) and prior coronary artery bypass grafting (CABG) was performed to determine impact of comorbidities and haemodynamic modulation on collateral recruitment. Subsequent systematic reviews and meta-analyses were performed. Invasive haemodynamic assessment of coronary blood flow and pressure in the presence and absence of collaterals was correlated with endothelial, haematological, biochemical and proteomic markers in both human and animal studies. Results: The important and novel findings are; - The presence of acutely recruited robust collaterals in the setting of STEMI are associated with a reduction in mortality and improved left ventricular function. - In the setting of a CTO, robust collaterals do not reduce mortality or risk of future ischaemic events, but do increase likelihood of successful percutaneous revascularisation. - Collateral maturation is driven by an elevation in shear stress, alterations in blood flow and tissue ischaemia. - The presence of collaterals results in a consistent increase in coronary blood flow in the donor vessel, with resultant effect on both pressure and flow derived indices of ischaemia assessment commonly used in clinical practice. - Recruitment and maturation of coronary collaterals are associated with upregulation of endothelial derived chemoattractant proteins, growth factors and transcription factors. - Coronary artery bypass grafting to a donor vessel, results in poorer collateral recruitment, likely driven by alterations in coronary blood flow and endothelial shear stress - The presence of OSA is associated with more robust coronary collaterals in both the setting of STEMI and CTO, however in more severe forms of OSA, characterised by severe and prolonged hypoxia, collateral recruitment is attenuated. Conclusions: Coronary collaterals impart significant prognostic implications in the setting of acute and chronic coronary artery disease, recruited as a result of alterations in coronary haemodynamics and tissue ischaemia with resultant downstream activation of growth factors, chemokines and transcription factors. Ongoing research is necessary to determine whether this prognostic advantage can be translated into meaningful therapeutic targets along with a greater understanding of clinical implications of collaterals