Clinical outcome, echocardiographic assessment, neurohormonal and collagen turnover markers in low-fl ow severe aortic stenosis with high transvalvular gradient

Abstract

INTRODUCTION Patients with severe aortic stenosis (AS), high mean gradient (HMG), and preserved left ventricular ejection fraction (LVEF) may present with paradoxical "low flow" (LF). OBJECTIVES The aim of the study was to assess the potential effect of cardiac collagen metabolism on the HMG/LF phenomenon in patients with severe AS and to determine a clinical and echocardiographic pattern of these patients. PATIENTS AND METHODS We assessed a clinical status of 89 patients, aged over 64 years, with severe AS, HMG, and preserved LVEF (≥50%). Cardiac structure and function as well as systemic arterial hemodynamics were assessed with echocardiography, conventional Doppler, and tissue Doppler imaging. Moreover, plasma levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), procollagen III N-terminal propeptide (PIIINP), carboxyterminal telopeptide of collagen type I, matrix metallopeptidase 9, and inhibitor of matrix metalloproteinase type 1 were evaluated. We analyzed 2 groups of patients: with normal flow (stroke volume index [SVI], ≥35 ml/m 2 ; n = 70) and with LF (SVI, <35 ml/m 2 ; n = 19). RESULTS Patients with LF were older, had a larger left atrium and left atrial volume index, smaller aortic valve area, lower energy loss index, stroke work, mitral flow E velocity, mitral annular E' and S' velocities and systemic arterial compliance, higher relative left ventricular wall thickness, E/E', systemic arterial resistance and valvulo-arterial impedance. We observed a correlation between SVI and NT-proBNP, PIIINP, and selected parameters of cardiac structure and function. CONCLUSIONS In patients with severe AS, HMG and preserved LVEF, the LF is related to a more severe obstruction, altered aortic hemodynamics, cardiac dysfunction, and higher blood levels of NT-proBNP. An inverse association between PIIINP and SVI may indicate enhanced tissue fibrosis as an underlying pathology.

Is there any benefit from evaluation of exercise NT-proBNP concentrations in asymptomatic patients with severe high-gradient aortic stenosis?

“…17 In evaluating the severity of valvular heart disease, a sensitive biomarker would be very useful, potentially providing support to clinical management in asymptomatic patients with AS. 8,12,18 A previous study found that AS is strongly associated with increased NT-proBNP levels.…”

Severe Aortic Valve Stenosis and Pulmonary Hypertension: A Systematic Review of Non-Invasive Ways of Risk Stratification, Especially in Patients Undergoing Transcatheter Aortic Valve Replacement

“…Although CITP and PIIINP were found to be strongly associated with HF, especially HFrEF and cardiac dysfunction, circulating collagen metabolites were not accurate surrogate biomarkers for myocardial fibrosis in patients with AS [114]. However, the concentration of circulating PIIINP correlated positively with PAWP and inversely with LV ejection fraction and stroke volume index [115]. At the same time, downregulated expression of microRNA-19b, which elucidates collagen fibril cross-linking, predicted altered myocardial collagen network in AS patients, especially in those who had HF [116].…”

Aortic stenosis: new pathophysiological mechanisms and their therapeutic implications

“…Using the optimum NT-proBNP cut-off point of 515 pg/ml, they reported event-free survival rates at 1 and 2 years of 93% and 57%, respectively, in patients with NT-proBNP levels of less than 515 pg/ ml, compared with 50% and 31%, respectively, in those with NT-proBNP levels exceeding 515 pg/ml. 32 The authors concluded that the measurement of NT-proBNP provides valuable prognostic information in patients with asymptomatic moderate-to-severe AS.In a subset of patients with severe AS, high gradient, and preserved systolic function, Piestrzeniewicz et al 33 found low transvalvular flow to be related to high blood levels of NT-proBNP. In addition, they found an inverse relation between procollagen III N-terminal propeptide and stroke volume index, indicating enhanced tissue fibrosis as an underlying pathology.…”

“…In a subset of patients with severe AS, high gradient, and preserved systolic function, Piestrzeniewicz et al 33 found low transvalvular flow to be related to high blood levels of NT-proBNP. In addition, they found an inverse relation between procollagen III N-terminal propeptide and stroke volume index, indicating enhanced tissue fibrosis as an underlying pathology.…”