BACKGROUND: Coronary flow reserve (CFR) is progressively impaired with aortic stenosis (AS) severity. However, there is a broad range of CFR in patients with severe AS, and the factors responsible for this variability are weakly characterized. The aim of this study was to assess the correlates of noninvasive CFR in patients with severe AS (≤1 cm(2) or ≤0.6 cm(2)/m(2)) and preserved left ventricular (LV) ejection fractions (LVEFs) (>50%). METHODS: Sixty-six consecutive patients (mean age, 74 ± 11 years; 31 women; mean LVEF, 69 ± 10%) with isolated severe AS (mean, 0.75 ± 0.2 cm(2) and 0.42 ± 0.1 cm(2)/m(2)), without coronary artery disease, underwent prospectively Doppler transthoracic echocardiography including CFR measurement in the distal part of the left anterior descending coronary artery (LAD) with intravenous adenosine infusion (140 μg/kg/min over 2 min). CFR was defined as hyperemic peak LAD flow velocity divided by baseline flow velocity. Twenty controls matched for age and gender served as a comparative group. Plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) was also assessed. RESULTS: Compared with controls, patients with AS had higher baseline LAD flow velocities (36 ± 11 vs 27 ± 6 cm/sec, P < 0.01), lower hyperemic LAD flow velocities (80 ± 20 vs 89 ± 18 cm/sec, P = .09), and consequently lower CFR (2.3 ± 0.7 vs 3.3 ± 0.7, P < .01). In patients with AS, there were significant inverse correlations between CFR and age, E/e', indexed LV mass, NT-proBNP, pulmonary artery systolic pressure (PASP), baseline LV rate-pressure product, heart rate, and indexed left atrial volume and a significant positive correlation between CFR and LVEF (all P values < .05). Furthermore, compared with patients with asymptomatic AS (n = 22), those with symptomatic AS had more severely impaired CFR (2.15 ± 0.6 vs 2.7 ± 0.65), and higher NT-proBNP values (all P values < .05). In multivariate analysis, NT-proBNP, PASP, and LV rate-pressure product were the main independent correlates of CFR (all P values ≤ .01), and PASP was independently predicted by E/e' and indexed left atrial volume (all P values < .01). CONCLUSIONS: In patients with severe AS and preserved LVEFs, there is a relatively broad range of CFR values. CFR is more severely impaired in patients with symptomatic AS and is mainly linked with NT-proBNP, a surrogate of increased LV wall stress, workload as measured by LV rate-pressure product, and PASP.
BACKGROUND: Coronary flow reserve (CFR) is progressively impaired with aortic stenosis (AS) severity. However, there is a broad range of CFR in patients with severe AS, and the factors responsible for this variability are weakly characterized. The aim of this study was to assess the correlates of noninvasive CFR in patients with severe AS (≤1 cm(2) or ≤0.6 cm(2)/m(2)) and preserved left ventricular (LV) ejection fractions (LVEFs) (>50%). METHODS: Sixty-six consecutive patients (mean age, 74 ± 11 years; 31 women; mean LVEF, 69 ± 10%) with isolated severe AS (mean, 0.75 ± 0.2 cm(2) and 0.42 ± 0.1 cm(2)/m(2)), without coronary artery disease, underwent prospectively Doppler transthoracic echocardiography including CFR measurement in the distal part of the left anterior descending coronary artery (LAD) with intravenous adenosine infusion (140 μg/kg/min over 2 min). CFR was defined as hyperemic peak LAD flow velocity divided by baseline flow velocity. Twenty controls matched for age and gender served as a comparative group. Plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) was also assessed. RESULTS: Compared with controls, patients with AS had higher baseline LAD flow velocities (36 ± 11 vs 27 ± 6 cm/sec, P < 0.01), lower hyperemic LAD flow velocities (80 ± 20 vs 89 ± 18 cm/sec, P = .09), and consequently lower CFR (2.3 ± 0.7 vs 3.3 ± 0.7, P < .01). In patients with AS, there were significant inverse correlations between CFR and age, E/e', indexed LV mass, NT-proBNP, pulmonary artery systolic pressure (PASP), baseline LV rate-pressure product, heart rate, and indexed left atrial volume and a significant positive correlation between CFR and LVEF (all P values < .05). Furthermore, compared with patients with asymptomatic AS (n = 22), those with symptomatic AS had more severely impaired CFR (2.15 ± 0.6 vs 2.7 ± 0.65), and higher NT-proBNP values (all P values < .05). In multivariate analysis, NT-proBNP, PASP, and LV rate-pressure product were the main independent correlates of CFR (all P values ≤ .01), and PASP was independently predicted by E/e' and indexed left atrial volume (all P values < .01). CONCLUSIONS: In patients with severe AS and preserved LVEFs, there is a relatively broad range of CFR values. CFR is more severely impaired in patients with symptomatic AS and is mainly linked with NT-proBNP, a surrogate of increased LV wall stress, workload as measured by LV rate-pressure product, and PASP.