Genetic polymorphisms and immunologic profiles in arteriogenesis

Obstructive coronary artery disease brings along morbidity and mortality in
millions of patients worldwide. Despite the success of techniques like
retrograde revascularization by coronary artery bypass grafting (CABG) and
antegrade revascularization by percutaneous coronary intervention (PCI), these
forms of treatment are not suited for all patients due to complexity of the
lesions or co-morbidity and high surgical risks. Therefore new alternative
treatment options are warranted to alleviate symptoms and improve survival and
quality of life in these estimated 20% of patients without revascularization
options. One of the body*s physiologic mechanisms to maintain tissue perfusion
is the growth of collateral vessels. Due to an increasing gradient in the
presence of a arterial stenosis, the caliber of pre-existing collateral vessel
is increased, This process is known as arteriogenesis and is in concept the
prototype of retrograde vascularization using natural bypasses already present
in myocardial tissue. This potent process is capable to largely compensate for
perfusion deficits in coronary artery disease (CAD) and its mechanisms have
been under extensive research in the past decades. Coronary collaterals are
already prevalent in some extent in every person, but there are great
differences in the arteriogenic response between individuals. These differences
have been attributed to both genetic variation (i.e. polymorphism) and
immunologic phenotype. Interestingly, only about one third of the patients with
obstructive coronary artery disease develops a fully functional collateral
circulation. Especially in patients with a chronic total occlusion (CTO), where
one of the coronary arteries is fully occluded for >=3 months and downstream
vital myocardium is fully dependent on collateral perfusion. This collateral
perfusion can be determined by the collateral flow index (CFI). By measuring
the pressure gradient between the aortic pressure and the post CTO coronary
wedge pressure, CFI can be calculated. In this way CFI is directly correlated
with the amount of collateral perfusion and thereby arteriogenesis. Analyzing
the correlations between CFI with both genetic an immunologic profile helps us
further unravel the mechanisms of arteriogenesis, thereby opening the way for
possible future clinical applications.

Determining the role and influence of genetics, their polymorphisms and
immunologic phenotype in arteriogenesis in patients with obstructive coronary
artery disease (CAD).

This study is designed as a single center prospective cohort study.

The burden of the research is small. Patients included in the study will
undergo a single additional invasive measurement following the PCI.
Furthermore, 120ml blood will be taken for lab investigation, and patients will
undergo MRI and PET scans. The risks are minimal. The intracoronoary
pressure-flow measurement is a single invasive procedure like many which are
done in every standard PCI procedure, the risk of which are <1%.