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Trans-myocardial Extraction of Endothelin-1 Correlates with Increased Microcirculatory Resistance following
George R Abraham1,2, Duuamene Nyimanu2, Rhoda E Kuc2
1Royal Papworth Hospital NHS Foundation Trust, Cambridge, UK.
Insights
Endothelin-1 (ET-1) levels rise after percutaneous coronary intervention (PCI), and increased ET-1 extraction by the heart muscle contributes to coronary microvascular dysfunction (CMD). This finding highlights ET-1's role in post-PCI microvascular resistance.
Area of Science:
- Cardiology
- Vascular Biology
- Interventional Cardiology
Background:
- Coronary microvascular dysfunction (CMD) can complicate percutaneous coronary intervention (PCI).
- Endothelin-1 (ET-1), a potent vasoconstrictor, may mediate CMD post-PCI.
- Understanding ET-1's role requires evaluating its peri-procedural trans-myocardial gradient (TMG).
Purpose of the Study:
- To define the peri-procedural trans-myocardial gradient (TMG) of ET-1 and its precursor, Big ET-1.
- To assess the correlation between ET-1 TMG and pressure-wire indices of CMD, including coronary flow reserve (CFR) and index of microvascular resistance (IMR).
Main Methods:
- Paired blood samples were collected from the aortic root and coronary sinus before and after PCI in stable angina patients.
- Plasma ET-1 and Big ET-1 levels were quantified using enzyme-linked immunosorbent assay.
- ET-1 TMG was correlated with pressure-wire derived CFR and IMR.
Main Results:
- Both ET-1 and Big ET-1 levels increased significantly in the aorta and coronary sinus post-PCI.
- A negative shift in ET-1 TMG post-PCI indicated significantly increased myocardial extraction.
- Increased ET-1 trans-myocardial extraction correlated with higher IMR and increased hyperemic transit time.
Conclusions:
- Circulating ET-1 levels increase following PCI.
- Upregulated ET-1 trans-myocardial extraction contributes to elevated microcirculatory resistance post-PCI.
- ET-1 plays a significant role in the pathophysiology of coronary microvascular dysfunction after PCI.
Objective:
Coronary microvascular dysfunction (CMD) can complicate successful percutaneous coronary intervention (PCI). The potent endogenous vasoconstrictor peptide Endothelin-1 (ET-1) may be an important mediator. To investigate the mechanism, we sought to define the peri-procedural trans-myocardial gradient (TMG-coronary sinus minus aortic root levels) of ET-1 and its precursor peptide - Big ET-1. We then assessed correlation with pressure-wire indices of CMD: coronary flow reserve (CFR) and index of microvascular resistance (IMR).
Methods:
Paired blood samples from the guide catheter and coronary sinus were collected before and after pressure-wire-guided PCI from patients with stable angina. Plasma was analysed using a specific enzyme-linked immunosorbent assay for quantification of ET-1 peptides and correlated with pressure-wire data. Non normally distributed continuous variables are presented as median [IQR].
Results:
ET-1 and Big ET-1 increased post-PCI in the aorta (ET-1: 0.98 [0.76-1.26] pg/ml to 1.20 [1.03-1.67] pg/ml, P < 0.001 and Big ET-1: 2.74 [1.78-2.50] pg/ml to 3.36 [2.33-3.97] pg/ml, P < 0.001) and coronary sinus (ET-1: 1.00 [0.81-1.28] pg/ml to 1.09 [0.91-1.30] pg/ml, P = 0.03 and Big ET-1: 2.89 [1.95-3.83] pg/ml to 3.56 [2.66-4.83] pg/ml, P = 0.01). TMG of ET-1 shifted negatively compared with baseline following PCI reflecting significantly increased extraction (0.03 [-0.12-0.17] pg/ml pre-PCI versus -0.16 [-0.36-0.07] pg/ml post-PCI, P = 0.01). Increased ET-1 trans-myocardial extraction correlated with higher IMR (Pearson's r = 0.293, P = 0.02) and increased hyperemic transit time (Pearson's r = 0.333, P < 0.01). In subgroup analysis, mean ET-1 trans-myocardial extraction was higher amongst patients with high IMR compared with low IMR (0.73 pg/ml, SD:0.78 versus 0.17 pg/ml, SD:0.42, P = 0.02). There was additionally a numerical trend towards increased ET-1 trans-myocardial extraction in subgroups of patients with low CFR and in patients with Type 4a Myocardial Infarction, albeit not reaching statistical significance.
Conclusions:
Circulating ET-1 increases post-PCI and upregulated ET-1 trans-myocardial extraction contributes to increased microcirculatory resistance.
