View largeDownload slide View largeDownload slide This editorial refers to ‘Impact of low stroke volume on mortality in patients with severe aortic stenosis and preserved left ventricular ejection fraction’†, by D. Rusinaru et al., on page 1992. The echocardiographic diagnosis of severe aortic stenosis (AS) is based on peak aortic jet velocity ≥4 m/s and mean aortic valve gradient ≥40 mmHg on continuous wave Doppler data and an aortic valve area <1 cm2 (indexed aortic valve area ≤0.6 cm2/m2).1 The peak aortic jet velocity and the mean aortic valve gradient are flow-dependent measurements: these parameters increase when the flow rate through the aortic valve is high and decrease when the aortic valve flow is low for the same aortic valve orifice area. The aortic valve area is calculated based on the continuity equation which considers that the stroke volume (SV) ejected by the left ventricle is equal at the level of the left ventricular (LV) outflow tract and at the level of the stenotic aortic valve orifice (Take home figure). The SV at the level of the LV outflow tract is calculated as the cross-sectional area of the LV outflow tract times the flow velocity over the ejection period (velocity time integral obtained from tracing the envelope of the pulsed wave Doppler spectral signal).1 Therefore, LV SV seems to be an important component in the characterization of patients with AS since it influences peak jet velocity and mean transaortic gradient, and the calculation of aortic valve area. Take home figure View largeDownload slide Characterization of severe aortic stenosis with preserved left ventricular ejection fraction (LVEF). Example of a 78-year-old female with low-flow low-gradient severe aortic stenosis with preserved LVEF (C). The left ventricular outflow tract (LVOT) measured on the parasternal long-axis view below the insertion point of the aortic cusps is 20 mm (A). The short-axis view of the aortic valve shows calcified tricuspid valve with reduced opening (B). The peak jet velocity and mean transvalvular gradient on continuous wave Doppler are 2.8 m/s and 21 mmHg, respectively, indicating low gradient (D). The pulsed wave Doppler obtained in the apical five-chamber view shows reduced left ventricular stroke volume index (SVi), 32 mL/m2 (E). The calculated aortic valve area (AVA) is 0.9 cm2 (indexed, AVAi 0.53 cm2/m2). Take home figure View largeDownload slide Characterization of severe aortic stenosis with preserved left ventricular ejection fraction (LVEF). Example of a 78-year-old female with low-flow low-gradient severe aortic stenosis with preserved LVEF (C). The left ventricular outflow tract (LVOT) measured on the parasternal long-axis view below the insertion point of the aortic cusps is 20 mm (A). The short-axis view of the aortic valve shows calcified tricuspid valve with reduced opening (B). The peak jet velocity and mean transvalvular gradient on continuous wave Doppler are 2.8 m/s and 21 mmHg, respectively, indicating low gradient (D). The pulsed wave Doppler obtained in the apical five-chamber view shows reduced left ventricular stroke volume index (SVi), 32 mL/m2 (E). The calculated aortic valve area (AVA) is 0.9 cm2 (indexed, AVAi 0.53 cm2/m2). In patients with morphology of the aortic valve suggesting AS, current recommendations are first to evaluate the transaortic mean gradient.1 Patients with a high mean transaortic gradient (≥40 mmHg) usually have an aortic valve area <1 cm2 and the diagnosis of severe AS can be established. In these patients, aortic valve replacement is recommended if there are symptoms or reduction in LV ejection fraction (EF).2 In patients with a low transaortic mean gradient (<40 mmHg), the aortic valve area should be assessed: an aortic valve area >1 cm2 indicates moderate AS, whereas an aortic valve area <1 cm2 indicates the presence of low-gradient severe AS. One-third of the patients with severe AS have low transaortic gradients and pose a diagnostic and therapeutic dilemma. To characterize patients with low-gradient severe AS further, LV SV should be measured. Conventionally, an LV SV index ≤35 mL/m2 defines low-flow status.3 Patients with an LV SV index >35 mL/m2 are classified as normal-flow low-gradient severe AS. Patients with low-flow low-gradient severe AS are classified based on LVEF in paradoxical low-flow low-gradient severe AS (when LVEF is ≥50%) and classical low-flow low-gradient severe AS (if LVEF is <50%). While paradoxical low-flow low-gradient severe AS is usually characterized by severe LV hypertrophy with a small cavity and uncontrolled hypertension leading to reduced LV SV, in classical low-flow low-gradient severe AS, the low-flow status is caused by impaired LV contractility and frequently associated severe mitral regurgitation. Why is it important to consider flow status in patients with low-gradient severe AS? Several studies have shown that the clinical outcomes of patients with low-flow low-gradient severe AS are as poor as those reported in patients with high-gradient severe AS if left unoperated.3–6 In contrast, the clinical outcomes of patients with normal-flow low-gradient severe AS are comparable with those of patients with moderate AS and they can be conservatively managed.7,8 However, the cut-off value to define flow status was set arbitrarily.3 In the current issue of the European Heart Journal, Rusinaru and colleagues provide further insight into the association between flow status and prognosis in patients with severe AS and preserved LVEF.9 A total of 1645 individuals with no structural heart disease and 1450 patients with severe AS and preserved LVEF were evaluated. From the cohort of individuals without structural heart disease, the normal reference values of the LV SV index were derived (median 37.3 mL/m2). Thus, it could be considered that the current cut-off value to define low (<35 mL/m2) or normal (≥35 mL/m2) flow status is rather accurate. The cohort of patients with severe AS and preserved LVEF were divided according to an LV SV index <30 mL/m2, between 30 and 35 mL/m2, and >35 mL/m2, representing 13, 15, and 72% of patients, respectively. During a median follow-up of 38 months, 1072 patients underwent aortic valve replacement and 440 died. Severe AS patients with an LV SV index <30 mL/m2 had the lowest 5-year survival rates as compared with patients with an LV SV between 30 and 35 mL/m2 and >35 mL/m2 (53% vs. 69% and 72%, respectively; P < 0.001). On multivariate analysis, an LV SV index <30 mL/m2 was independently associated with higher risk of all-cause mortality as compared with the other groups, whereas there were no significant differences in risk between severe AS patients with an LV SV between 30 and 35 mL/m2 and patients with an LV SV index >35 mL/m2. These findings were also observed within the subgroup of patients with low-gradient severe AS. Current guidelines recommend aortic valve replacement in symptomatic low-flow low-gradient severe AS patients with reduced LVEF (class I) and preserved LVEF (class IIa) after careful confirmation of true severe AS.2 Echocardiographic measurement of LV SV is influenced by various technical factors (i.e. alignment of the ultrasound beam along the transaortic jet flow) and geometrical assumptions. The cross-sectional area of the LV outflow tract is considered circular based on two-dimensional echocardiography. This is an important source of error in the calculation of the aortic valve area. The measurement of the cross-sectional area of the LV outflow tract with three-dimensional imaging techniques may reclassify a significant number of severe AS patients into moderate AS.10 In addition, in patients with reduced LVEF, the aortic valve area should be calculated after normalization of the LV SV with low-dose dobutamine. Ultimately, the calcium load of the aortic valve has been included in current recommendations as a valuable surrogate to define severe AS.1 The results of the present study open up the question of how to better understand the factors underlying low-flow severe AS in patients with preserved LVEF and their association with poor outcome. Late gadolinium contrast-enhanced magnetic resonance imaging studies have shown increasing myocardial reactive and replacement fibrosis in patients with severe AS that may lead to a stiffer and less compliant left ventricle, resulting in lower LV preload and LV SV.11 The presence of late gadolinium enhancement in the LV myocardium in severe AS patients has been associated with poor prognosis.11 Therefore, LV SV assessment is an important component in the diagnosis of AS and, in patients with preserved LVEF, LV SV is a reflector of the consequences of the stenotic aortic valve on the LV structure. Conflict of interest: The Department of Cardiology of the Leiden University Medical Center receives unrestricted research grants from Biotronik, Medtronic, Boston Scientific and Edwards Lifesciences. V.D. has received speaker fees from Abbott Vascular. J.J.B. has nothing to disclose. References 1 Baumgartner H, Hung J, Bermejo J, Chambers JB, Edvardsen T, Goldstein S, Lancellotti P, LeFevre M, Miller FJr, Otto CM. Recommendations on the echocardiographic assessment of aortic valve stenosis: a focused update from the European Association of Cardiovascular Imaging and the American Society of Echocardiography. Eur Heart J Cardiovasc Imaging 2017; 18: 254– 275. Google Scholar CrossRef Search ADS PubMed 2 Baumgartner H, Falk V, Bax JJ, De Bonis M, Hamm C, Holm PJ, Iung B, Lancellotti P, Lansac E, Rodriguez MD, Rosenhek R, Sjogren J, Tornos MP, Vahanian A, Walther T, Wendler O, Windecker S, Zamorano JL. 2017 ESC/EACTS Guidelines for the management of valvular heart disease. Eur Heart J 2017; 38: 2739– 2791. Google Scholar CrossRef Search ADS PubMed 3 Hachicha Z, Dumesnil JG, Bogaty P, Pibarot P. Paradoxical low-flow, low-gradient severe aortic stenosis despite preserved ejection fraction is associated with higher afterload and reduced survival. Circulation 2007; 115: 2856– 2864. Google Scholar CrossRef Search ADS PubMed 4 Capoulade R, Le VF, Clavel MA, Dumesnil JG, Dahou A, Thebault C, Arsenault M, O’Connor K, Bedard E, Beaudoin J, Senechal M, Bernier M, Pibarot P. Echocardiographic predictors of outcomes in adults with aortic stenosis. Heart 2016; 102: 934– 942. Google Scholar CrossRef Search ADS PubMed 5 Clavel MA, Dumesnil JG, Capoulade R, Mathieu P, Senechal M, Pibarot P. Outcome of patients with aortic stenosis, small valve area, and low-flow, low-gradient despite preserved left ventricular ejection fraction. J Am Coll Cardiol 2012; 60: 1259– 1267. Google Scholar CrossRef Search ADS PubMed 6 Kamperidis V, van Rosendael PJ, Ng AC, Katsanos S, van der Kley F, Debonnaire P, Joyce E, Sianos G, Marsan NA, Bax JJ, Delgado V. Impact of flow and left ventricular strain on outcome of patients with preserved left ventricular ejection fraction and low gradient severe aortic stenosis undergoing aortic valve replacement. Am J Cardiol 2014; 114: 1875– 1881. Google Scholar CrossRef Search ADS PubMed 7 Eleid MF, Sorajja P, Michelena HI, Malouf JF, Scott CG, Pellikka PA. Flow-gradient patterns in severe aortic stenosis with preserved ejection fraction: clinical characteristics and predictors of survival. Circulation 2013; 128: 1781– 1789. Google Scholar CrossRef Search ADS PubMed 8 Mehrotra P, Jansen K, Flynn AW, Tan TC, Elmariah S, Picard MH, Hung J. Differential left ventricular remodelling and longitudinal function distinguishes low flow from normal-flow preserved ejection fraction low-gradient severe aortic stenosis. Eur Heart J 2013; 34: 1906– 1914. Google Scholar CrossRef Search ADS PubMed 9 Rusinaru D, Bohbot Y, Ringle A, Maréchaux S, Diouf M, Tribouilloy C. Impact of low stroke volume on mortality in patients with severe aortic stenosis and preserved left ventricular ejection fraction. Eur Heart J 2018; 39: 1992– 1999. 10 Kamperidis V, van Rosendael PJ, Katsanos S, van der Kley F, Regeer M, Al Amri I, Sianos G, Marsan NA, Delgado V, Bax JJ. Low gradient severe aortic stenosis with preserved ejection fraction: reclassification of severity by fusion of Doppler and computed tomographic data. Eur Heart J 2015; 36: 2087– 2096. Google Scholar CrossRef Search ADS PubMed 11 Chin CWL, Everett RJ, Kwiecinski J, Vesey AT, Yeung E, Esson G, Jenkins W, Koo M, Mirsadraee S, White AC, Japp AG, Prasad SK, Semple S, Newby DE, Dweck MR. Myocardial fibrosis and cardiac decompensation in aortic stenosis. JACC Cardiovasc Imaging 2017; 10: 1320– 1333. Google Scholar CrossRef Search ADS PubMed Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: firstname.lastname@example.org. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)
European Heart Journal – Oxford University Press
Published: May 16, 2018
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