Abnormal coronary microvascular endothelial function in humans with asymptomatic left ventricular dysfunction

Background Coronary endothelial dysfunction may potentially lead to myocardial ischemia and to the progression of heart failure. Though endothelial dysfunction is associated with advanced heart failure in humans, relatively little is known regarding their temporal relationship. Thus, the current study was designed to test the hypothesis that coronary endothelial dysfunction is present in patients with asymptomatic left ventricular dysfunction. Methods and results Three hundred patients without symptoms of heart failure, with normal or mildly diseased coronary arteries at angiography underwent coronary vascular reactivity evaluation using intracoronary adenosine, acetylcholine (ACH) and nitroglycerin. Patients were divided into 2 groups based on the left ventricular ejection fraction (EF): patients with asymptomatic left ventricular dysfunction (ALVD), EF <45% (n = 11); and patients with EF ≥45% (n = 289, controls). Except for a lower high-density lipoprotein level in patients with ALVD, there were no significant differences between the groups in regards to conventional cardiovascular risk factors. There was no difference in the change (mean ± SE) in epicardial diameter in response to ACH (−21.7% ± 7.2% vs −13.8% ± 1.5%, P = .3). The change in coronary blood flow in response to ACH was significantly attenuated in the patients with ALVD when compared to the controls (−18.5% ± 14.9% vs 74.0% ± 7.2%, P < .013). By multivariate analysis, EF was an independent predictor of coronary microvascular dilation with ACH (P < .001). Conclusion The current study demonstrates that coronary microvascular endothelial dysfunction is present in ALVD. Thus, coronary endothelial dysfunction may be an early event in the pathophysiology of heart failure.