Impaired Coronary Autoregulation Is Associated With Long-term Fatal Events in Patients With Stable Coronary Artery Disease

Abstract

Background— Abnormalities in the coronary microcirculation are increasingly recognized as an elementary component of ischemic heart disease, which can be accurately assessed by coronary flow velocity reserve in reference vessels (refCFVR). We studied the prognostic value of refCFVR for long-term mortality in patients with stable coronary artery disease. Methods and Results— We included patients with stable coronary artery disease who underwent intracoronary physiological evaluation of ≥1 coronary lesion of intermediate severity between April 1997 and September 2006. RefCFVR was assessed if a coronary artery with <30% irregularities was present. RefCFVR >2.7 was considered normal. Patients underwent revascularization of all ischemia-causing lesions. Long-term follow-up was performed to document the occurrence of (cardiac) mortality. RefCFVR was determined in 178 patients. Kaplan–Meier estimates of 12-year all-cause mortality were 16.7% when refCFVR >2.7 and 39.6% when refCFVR ≤2.7 ( P <0.001), whereas Kaplan–Meier estimates for cardiac mortality were 7.7% when refCFVR >2.7 and 31.6% when refCFVR ≤2.7 ( P <0.001). After multivariable adjustment, refCFVR ≤2.7 was associated with a 2.24-fold increase in all-cause mortality hazard (hazard ratio, 2.24; 95% confidence interval, 1.13–4.44; P =0.020) and a 3.32-fold increase in cardiac mortality hazard (hazard ratio, 3.32; 95% confidence interval, 1.27–8.67; P =0.014). Impairment of refCFVR originated from significantly higher baseline flow velocity in the presence of significantly lower reference vessel baseline microvascular resistance ( P <0.001), indicating impaired coronary autoregulation as its cause. Conclusions— In patients with stable coronary artery disease, impaired refCFVR, resulting from increased baseline flow velocity indicating impaired coronary autoregulation, is associated with a significant increase in fatal events at long-term follow-up.

Physiological Basis and Long-Term Clinical Outcome of Discordance Between Fractional Flow Reserve and Coronary Flow Velocity Reserve in Coronary Stenoses of Intermediate Severity

“…Notably, in patients in whom CFVR was abnormal, a decreased Because normal coronary autoregulatory function would provide compensatory vasodilation only to the point necessary to maintain stable coronary flow, 4 an increase in basal coronary flow in this setting suggests that coronary autoregulation is disturbed. 13,23,26 Such disturbed autoregulation is consistent with an important role of microvascular (dys)function in the discordance between FFR and CFVR and may be attributed to structural vascular adaptation in the setting of microvascular disease or in the setting of chronic deprivation of perfusion pressure in the presence of substantial epicardial disease.…”

“…[11][12][13] Moreover, the presence of microvascular disease may unaccountedly obscure the information on functional epicardial stenosis severity derived from coronary pressure measurements.…”

“…We have reported recently that abnormalities in microvascular function under basal autoregulation conditions, in the absence of hyperemic blood flow impairment, impart a particularly important risk for long-term adverse events, both in patients with stable coronary artery disease 13 and in patients after primary PCI for ST-segment-elevation myocardial infarction. 12 Moreover, the previously mentioned noninvasive imaging studies support this hypothesis, because both studies indicate that an abnormal coronary flow reserve in the presence of normal hyperemic perfusion, indicating alterations in basal flow, is an important marker for adverse outcome.…”

Clinical Quantification of Myocardial Blood Flow Using PET: Joint Position Paper of the SNMMI Cardiovascular Council and the ASNC

“…FFR can appear falsely normal in the presence of microvascular dysfunction or disease, since elevated pressure distal to a critical stenosis, associated with increased resistance due to a microvascular abnormality, may result in a normal pressure drop across a hemodynamically significant lesion. 193,194 Further, in the presence of diffuse atherosclerosis, FFR may be abnormal even without focal stenosis. 195 Finally, in the setting of excellent flow capacity, the clinical significance of a reduced FFR across a moderate lesion may be overestimated if peak flow is still sufficient to meet myocardial oxygen demand.…”

“…The discordance of low MFR with normal FFR is most commonly due to microvascular disease in the setting of diffuse nonobstructive epicardial disease or in isolation. 193,194 Thus, both FFR and MFR provide valuable physiologic information for patient management but assess different pathophysiologic processes. Knowledge of these differences is important in understanding the frequently observed discordance between these measurements.…”