INFLUENCE OF INTIMAL THICKENING ON CORONARY BLOOD-FLOW RESPONSES IN ORTHOTOPIC HEART-TRANSPLANT RECIPIENTS - A COMBINED INTRAVASCULAR DOPPLER AND ULTRASOUND IMAGING STUDY

Background Intravascular ultrasound imaging detects epicardial intimal thickening in the majority of heart transplant recipients with angiographically normal epicardial coronary arteries. Although coronary artery vasoreactivity is abnormal after cardiac transplantation, intimal thickening does not appear to affect conduit vessel responses. However, the effect of intimal thickening on both conduit and resistance vessel responses, as measured by changes in volumetric coronary blood flow (CBF), is unknown. Methods and Results Epicardial coronary artery conductance and microvascular resistance vessel responses were studied after intracoronary adenosine and nitroglycerin administration in 36 orthotopic heart transplant recipients 1 month to 7 years after transplantation. Sequentially measured coronary flow average peak velocity ([APV, cm/s] 0.018 in Doppler guide wire) and epicardial luminal cross-sectional area ([CSA, mm(2)] 4.3F 30-MHz ultrasound catheter) data were obtained at baseline and during peak hyperemia after administration of 12 to 18 mu g IC adenosine and 150 to 200 mu g IC nitroglycerin. Volumetric CBF (mL/min) was calculated as CBF=APV (cm/s) x CSA (mm(2)) x 60 seconds/1 min x 1 cm(2)/100 mm(2) x 0.5. Measurements were made from a discrete position in the proximal left anterior descending (LAD) artery (n=22), mid-LAD artery (n=7), proximal circumflex artery (n=6), and proximal right coronary artery (n=1). Intimal thickening was present in 19 of 32 patients (60%). Both adenosine and nitroglycerin increased APV (from 18.9+/-4.9 to 56.0+/-11.5 cm/s for adenosine and from 20.2+/-5.3 to 49.1+/-11.5 cm/s for nitroglycerin; both P<.05). Coronary flow velocity reserve was significantly higher for adenosine compared with nitroglycerin (3.1+/-0.6 versus 2.5+/-0.7, respectively; P<.001). Epicardial luminal CSA was unchanged during adenosine hyperemia compared with baseline (17.4+/-3.8 versus 17.3+/-4.0 mm(2), respectively; P=NS) but was significantly greater during nitroglycerin hyperemia compared with baseline (18.7+/-3.8 versus 17.3+/-4.0 mm(2), 6.2+/-3.6% change; P<.05). Baseline CBF was similar before drug administration. Hyperemic adenosine and nitroglycerin CBF responses (297+/-99 and 276+/-87 mL/min, respectively; P=NS) and CBF reserve (3.0+/-0.7 and 2.7+/-0.7, respectively; P=NS) were not significantly different. Importantly, intimal thickening did not diminish resting or hyperemic APV, coronary flow velocity reserve, luminal CSA, CBF, or CBF reserve responses. Conclusions In this study of angiographically normal heart transplant recipients, epicardial intimal thickening does not diminish conduit and resistance vessel responses during endothelial-independent vasodilator administration.