Abstract

Cardiac allograft vasculopathy is a common phenomenon in epicardial and microvascular vessels. Intramyocardial vessel disease may lead to small, stellate infarcts. The present study tested the impact of microvascular vasomotor function on changes in left ventricular systolic function in the long-term follow-up after cardiac transplantation. Seventeen consecutive cardiac transplant patients, 40+/-21 months after cardiac transplantation, without angiographically visible cardiac allograft vasculopathy and without episodes of acute rejection were included in the study. Coronary microvascular reactivity was assessed by the endothelium-dependent stimulus acetylcholine (50 microg i.c.) and by the endothelium-independent stimulus dipyridamole (0.56 mg/kg i.v.) utilizing an Doppler catheter. Radionuclide ventriculography was performed at the time of coronary flow measurement and repeated 2 years later to correlate changes in left ventricular ejection fraction with the coronary flow reserve measurement 2 years previously. There was a statistically significant correlation between endothelium- independent coronary flow reserve to dipyridamole and changes in ejection fraction at rest (r=0.59; P < 0.01) and during exercise (r=0.48; P < 0.05). Twenty-four months later, patients with a coronary flow reserve to dipyridamole < 2.5 showed a significant decline in ejection fraction during exercise (-7 +/- 5%) compared to patients with a coronary flow reserve > 2.5 (1.1+/-5%; P=0.003). Coronary flow reserve to acetylcholine was not correlated with a reduced ejection fraction during exercise. Endothelium-independent microvascular dysfunction has prognostic importance for deterioration of left ventricular function in cardiac transplant recipients without angiographically visible coronary artery stenoses. These results reinforce the concept that microvascular and epicardial vessel disease after transplantation are two distinct entities with different functional consequences.

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