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Objective: There are no data about the prevalence of silent coronary artery disease in asymptomatic severe aortic stenosis patients with normal exercise testing. Importantly, unmasking significant coronary artery disease in patients with aortic stenosis could influence the choice/timing of treatment in these patients., Method: Exercise testing was performed on semi-supine ergobicycle. Cardiopulmonary analysis during exercise testing, echocardiography, and laboratory analysis at rest was done. Standard clinical/electrocardiography criteria were assessed for symptoms/signs of ischemia during/after exercise testing. In patients with normal exercise testing coronary angiography was performed using standard femoral/radial percutaneous approach. Coronary stenosis was considered significant if >70% of vessel diameter or 50%-70% with fractional flow reserve ≤0.8., Results: Total of 96 patients with normal exercise testing were included (67.6 years, 50.6% males). No patient had any complication or adverse event. The Pmean was 52.7 mmHg, mean indexed aortic valve area was 0.36 cm/m and left ventricular ejection fraction, 69.5%. 19/96 patients (19.8%) had significant coronary artery disease on coronary angiography. Multivariate logistic regression analysis revealed brain natriuretic peptide and blood glucose as independent predictors of silent coronary artery disease. Brain natriuretic peptide value of 118 pg/ml had sensitivity/specificity of 63%/73% for predicting coronary artery disease (area under the curve 0.727, P = 0.006)., Conclusion: Our results are the first to show that in patients with severe aortic stenosis, normal left ventricular ejection fraction,, and normal exercise testing, significant coronary artery disease is present in as many as 1/5 patients. In such patients, further prospective studies are warranted to address the diagnostic value of brain natriuretic peptide in detecting silent coronary artery disease.

Background and Aim: Coronary flow reserve is impaired in asymptomatic patients with aortic stenosis and has a prognostic value. We investigated whether the type II diabetes mellitus additionally impairs microvascular circulation assessed by coronary flow reserve in patients with asymptomatic severe aortic stenosis, normal left ventricular ejection fraction and nonobstructed coronary arteries., Methods: A total of 128 patients, mean age of 66.35 ± 10.51 (58.6% males), with severe aortic stenosis and normal left ventricular ejection fraction were enrolled in this study. Patients with diabetes mellitus, those who were treated for diabetes mellitus or had documentation confirming the diagnosis of diabetes mellitus, were considered. All patients underwent coronary angiography and had no obstructive coronary disease (defined as having no stenosis >50% in diameter), standard transthoracic Doppler-echocardiographic study and adenosine stress transthoracic echocardiography for coronary flow reserve measurement., Results: Diabetes mellitus was present in 26 patients (20.31%). There was no significant difference in aortic stenosis severity between diabetic and non-diabetic patients [aortic valve area (0.81 ± 0.18 vs 0.85 ± 0.15 cm(2)) and Vmax (4.20 ± 0.57 vs 4.21 ± 0.48 m/s)]. Mean coronary flow reserve in diabetic patients was 1.98 ± 0.48, while mean coronary flow reserve in non-diabetic patients was 2.64 ± 0.54 (p < 0.01). Diabetes mellitus was independent predictor of coronary flow reserve [B = -0.636, 95% confidence interval (-0.916 to -0.368), p < 0.001]., Conclusion: Diabetes mellitus additionally impairs coronary microvascular function in asymptomatic patients with severe aortic stenosis and nonobstructed coronary arteries., (© The Author(s) 2016.)

Aortic valve replacement (AVR) therapy is an obvious choice for symptomatic severe aortic stenosis (AS) patients as it improves symptoms, left ventricular function, and survival. The treatment decisions and indication for AVR in asymptomatic patients with severe AS and normal left ventricular ejection fraction are less well established and the subject of ongoing debate. Many efforts have been made to define the best treatment option in asymptomatic AS patients with normal left ventricular ejection fraction. Retrospective and observational data imply that elective AVR for asymptomatic severe AS may lead to improvement in outcomes in comparison to surgery performed after onset of symptoms. The AVATAR trial will aim to assess outcomes among asymptomatic AS patients randomized to either elective early AVR or medical management with vigilant follow-up. In the latter group, AVR would be delayed until either the onset of symptoms or changes in predefined echocardiographic parameters. To the best of the authors' knowledge, it will be the first large prospective, randomized, controlled, multicenter clinical trial that will evaluate the safety and efficacy of elective AVR in this specific group of patients., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background and Aim of the Study: Risk stratification is particularly complex in asymptomatic patients with significant aortic stenosis (AS). The study aim was to assess which hemodynamic/Doppler-echocardiographic parameter best predicts mortality in asymptomatic patients with severe AS and a normal left ventricular ejection fraction (LVEF)., Methods: This prospective study included 128 consecutive asymptomatic patients (75 males, 53 females; mean age 66.35 ± 10.51 years) with severe AS (aortic valve area (AVA) ± 1.0 cm2) and a normal LVEF (55%). The patients were followed up for 47 months (median 35.5 months, IQR 7 months). Clinical data at follow up were obtained from all patients by either direct examination or telephone interview., Results: During the follow up, 55 patients (43.0%) underwent aortic valve replacement (AVR) surgery due to AS-related symptoms. Of the 12 patients that died (9.4%), eight deaths occurred before surgery (four patients refused operation), and one patient died after surgery due to postoperative infection. Those patients who died had a significantly higher valvulo-arterial impedance (Z(va)) (7.81 versus 4.86 mmHg x ml/m2, p < 0.001), a higher N-terminal pro-brain natriuretic peptide (NT-proBNP) level (1708.5 versus 376.5 pg/ml, p = 0.003) and a lower AVA (0.65 versus 0.86 cm2, p = 0.002), but there were no differences in LVEF, P(mean) or age between the groups (69.68% versus 72.24%, p = 0.206; 44.95 versus 41.75 mmHg; and 69 versus 66 years, p = 0.332, respectively). When parameters that were predictors of mortality according to univariate analysis were further analyzed with Cox multivariate analysis, Z(va) was found to be the best independent predictor (B = 0.460, HR = 1.584, 95% CI = 1.064-2.359, p = 0.024). A Z(va) value of 6.1 mmHg x ml/m2 was identified as the best (cut-off) predictive value for the occurrence of death, with a sensitivity 61.1% and a specificity 86.0%., Conclusion: Z(va) is the best mortality predictor in asymptomatic patients with severe AS and a normal LVEF. Future studies are required to focus further on predictors of outcome, the aim being to achieve an optimal selection of asymptomatic patients considered to be at risk and who would benefit from early AVR.

Aim: NT-proBNP has been shown to be a reliable biochemical marker for left ventricular wall stress. The relationship between NT-proBNP and coronary flow reserve (CFR) was evaluated in patients with significant asymptomatic aortic stenosis (AS)., Methods: A total of 74 patients with moderate or severe AS, mean age 66.68 ± 10.02 years (56.75% males), were enrolled in this prospective study. All patients underwent coronary angiography and had no obstructive coronary disease (defined as having no stenosis >50% in diameter). They had all undergone standard transthoracic Doppler-echo study and adenosine stress transthoracic-echo for CFR measurement and laboratory analysis for NT-proBNP measurement., Results: The median NT-proBNP value was significantly increased (417.0 pg/ml; interquartile range [IQR]: 176.8-962.2 pg/ml). NT-proBNP was significantly higher in the group with CFR ≤2.5 (median: 549.0 pg/ml; IQR: 311.5-1131.0 pg/ml; as opposed to median: 291.5 pg/ml; IQR: 123.0-636.2 pg/ml; W = 452; p = 0.012). NT-proBNP showed significant negative correlation with CFR (ρ = -0.377, p = 0.001). There was also significant correlation between NT-proBNP and E/E´, S´ and aortic valve resistance. The NT-proBNP value of 334.00 pg/ml was determined as the best cut-off value for the diagnosis of CFR ≤2.5 (area under the curve: 0.67; 95%CI: 0.54-0.79; p < 0.01) and the sensitivity and specificity were 74 and 64%, respectively., Conclusion: Elevated NT-proBNP can indicate patients with impaired CFR in asymptomatic moderate or severe AS patients with preserved ejection fraction and nonobstructive coronary arteries.