Incidence, progression and functional significance of cardiac allograft vasculopathy after heart transplantation.

BACKGROUND: Cardiac allograft vasculopathy after heart transplantation leads to an accelerated form of atherosclerosis with marked and often diffuse vessel wall changes that limit long-term survival. Previous studies showed contradictory results relating vessel wall changes to endothelial vasodilator response. METHODS: A total of 30 cardiac transplant recipients were studied 3, 12, and 24 months after heart transplantation. Coronary angiography was performed at rest, during supine bicycle ergometry, and after 1.6 mg sublingual nitroglycerin. Coronary cross-sectional area (biplane coronary angiography) and coronary artery wall changes (intravascular ultrasound) were assessed and extent of intimal changes correlated to vasodilator responses to nitroglycerine and bicycle ergometry. RESULTS: Intravascular ultrasound showed significant intimal thickening in 43, 64, and 58% of patients at 3, 12, and 24 months. Intimal thickening 3 months after transplantation was related to donor age (r=0.70, P<0.01) but did not predict progression of disease that manifested itself angiographically as a decrease in coronary cross-sectional area at 12 and 24 months (P<0.005) and significant coronary stenosis in 12% of patients after 24 months. Endothelium-independent vasodilatation after nitroglycerin (33+/-15, 44+/-20, and 43+/-24%) was normal. Endothelium-dependent, flow-induced vasodilatation during exercise was decreased (14+/-11, 18+/-14, and 16+/-17%) but did not correlate to intimal changes assessed by ultrasound. CONCLUSIONS: The study confirms the high incidence of intimal thickening after heart transplantation as assessed by intravascular ultrasound. Impaired exercise-induced vasodilatation suggests diminished bioavailability of endothelium-derived nitric oxide to physiological stimulation but the lack of relationship between coronary wall changes and this functional impairment suggests intermittent and presumably reversible endothelial injury in graft atherosclerosis.

Alpha-adrenoceptor blockade prevents exercise-induced vasoconstriction of stenotic coronary arteries.

OBJECTIVES: The study aimed to evaluate the role of alpha-adrenergic mechanisms during dynamic exercise in both normal and stenotic coronary arteries. BACKGROUND: Paradoxical vasoconstriction of stenotic coronary arteries has been reported during dynamic exercise and may be due to several factors such as alpha-adrenergic drive, a decreased release of nitric oxide, platelet aggregation with release of serotonin, or a passive collapse of the vessel wall. METHODS: Twenty-six patients were studied at rest, during two levels of supine bicycle exercise and after 1.6 mg sublingual nitroglycerin. The alpha-blocker phentolamine was given to 16 patients before exercise, five of whom had also taken a beta-adrenergic-blocker the same morning. Ten patients served as controls. The cross-sectional areas of a normal and a stenotic coronary vessel were determined by biplane quantitative coronary arteriography. RESULTS: In the normal vessel segments, coronary cross-sectional area did not change after phentolamine injection, but increased in all patient groups similarly during exercise. Although coronary vasoconstriction existed in stenotic vessel segments in control patients, phentolamine-treated patients showed exercise-induced vasodilation without difference in patients with and without chronic beta-blockade. CONCLUSIONS: Exercise-induced vasoconstriction of stenotic coronary arteries is prevented by intracoronary administration of phentolamine. There was no difference in coronary vasomotion between patients receiving phentolamine alone and patients receiving phentolamine in addition to a beta-blocker. This finding suggests that exercise-induced vasoconstriction is mediated not only by endothelial dysfunction but also by alpha-adrenergic mechanisms.

Angina pectoris in patients with aortic stenosis and normal coronary arteries. Mechanisms and pathophysiological concepts.

BACKGROUND: The incidence of angina pectoris (AP) in patients with severe aortic stenosis (AS) and normal coronary arteries has been reported to be 30% to 40%. The exact pathophysiological mechanism, however, is not known. The purpose of this work was to evaluate the various hemodynamic and angiographic determinants of myocardial perfusion in 61 patients with severe AS. METHODS AND RESULTS: In a retrospective analysis, 61 patients with severe AS and without significant coronary artery disease were studied. Thirty-three patients with atypical chest pain and angiographically normal arteries served as control subjects. Patients were divided into two groups: 32 with AP and 29 without AP. Quantitative coronary angiography was performed in 59 patients and 22 control subjects. Coronary flow reserve was determined in 29 patients and 7 control subjects by use of coronary sinus thermodilution technique. Patients with AP had a lower left ventricular (LV) muscle mass, an increased LV peak systolic pressure, and increased wall stress than those without AP. Vessels of the left coronary artery were smaller and coronary flow reserve was lower in patients with AP than in those without. Inadequate L V hypertrophy with an increased wall stress was found in patients with AP but not in patients without AP. CONCLUSIONS: Myocardial ischemia in patients with severe AS can occur in the absence of coronary artery disease and appears to be due to inadequate LV hypertrophy with high systolic and diastolic wall stresses and a reduced coronary flow reserve. The cause of inadequate LV hypertrophy, however, remains unclear.