Impaired coronary flow reserve as a marker of microvascular dysfunction to predict long-term cardiovascular outcomes, acute coronary syndrome and the development of heart failure.

BACKGROUND: In the absence of obstructive coronary narrowing, impaired coronary flow reserve (CFR) represents coronary microvascular dysfunction. Transthoracic Doppler echocardiography (TTDE) allows non-invasive measurement of CFR in the left anterior descending (LAD) artery. This study aimed to assess the prognostic value of TTDE-derived CFR (as a marker of microvascular function) in predicting long-term cardiovascular events, acute coronary syndrome (ACS) events, and the development of heart failure (HF). METHODS AND RESULTS: This study consisted of 272 patients with coronary artery disease not involving obstructive narrowing (≥50%) in the LAD. Patients underwent TTDE examination for CFR measurement in the LAD. During the follow-up period of 4.0±1.9 years, 32 patients (12%) had cardiovascular events. Cox proportional hazard analysis identified lower CFR as an independent risk factor of cardiovascular events (P<0.001), ACS events (P=0.008), and HF development (P=0.003). A CFR less than 2.4 was the best cut-off value for predicting all events (area under the curve=0.82). CFR excellently predicted the development of HF (area under the curve=0.95), but not ACS events (area under the curve=0.67). CONCLUSIONS: This TTDE study demonstrated that CFR was a significant and independent determinant of long-term cardiovascular events, ACS events and HF in patients with coronary artery disease. A CFR greater than 2.0 was not suitable to predict a favorable long-term outcome, even in the absence of obstructive coronary narrowing.

Circadian variation in coronary flow velocity reserve and its relation to α1-sympathetic activity in humans.

BACKGROUND: The circadian change in coronary microvascular function has not been directly assessed in human beings. Recent advances in transthoracic Doppler echocardiography (TTDE) provide noninvasive, physiological assessment of coronary flow velocity reserve (CFVR). METHODS: This study consisted of 20 young healthy subjects (24 ± 2 years, 20 men) who underwent CFVR examinations at 3 different times; early morning (6AM), late morning (11AM) and late evening (10PM). The flow velocity in the distal portion of the left anterior descending coronary artery was measured with TTDE at baseline and during adenosine infusion to calculate CFVR. These examinations were repeated with the intake of α1-blocker (prazosin 1mg) on the other day. RESULTS: CFVR showed a circadian variation with an increase from the early morning to the late morning, following a decrease to the late evening thereafter (4.4 ± 0.9 at 6AM; 5.2 ± 1.3 at 11AM; 4.2 ± 1.1 at 10PM, p<0.001). In the study with α1-blocker, CFVR was comparable between the early morning and the late morning, whereas CFVR in the late evening was lower than those in other 2 time points (5.0 ± 1.1 at 6AM; 4.9 ± 0.9 at 11AM; 4.3 ± 0.9 at 10PM, p<0.001). CONCLUSIONS: This study demonstrates that CFVR has a circadian variation in humans, with an increase from the late evening to the late morning. Adding α1-blocker ameliorated CFVR only in the early morning, indicating that α1-sympathetic activity plays a heterogeneous and important role in the circadian change of CFVR in humans.

Comparison of coronary microcirculation in female nurses after day-time versus night-time shifts.

Nightshift work, which is known to cause mental stress and disrupt normal biological diurnal rhythms, leads to endothelial dysfunction resulting in increased risk for cardiovascular disease. This study aimed to investigate the acute effect of night-shift work on coronary microcirculation through assessment of coronary flow reserve (CFR) by transthoracic Doppler echocardiography. This study consisted of 36 women nurses who underwent transthoracic Doppler echocardiographic examinations after working a nightshift and on a regular day without previous nightshift work. Flow velocity in the distal portion of the left anterior descending coronary artery was measured at baseline and during adenosine infusion. CFR was calculated as the ratio of hyperemic to basal mean diastolic flow velocity. CFR after night work was lower than that on a regular workday (3.8 ± 0.6 vs 4.1 ± 0.6, p <0.001). Degree of decreases in CFR after night work was correlated to Framingham risk score (r = 0.35, p = 0.036). In conclusion, this study demonstrated that coronary microcirculation was impaired after nightshift work in women nurses.