Reply
Authors: Maurizio Cesari
Journal: Hepatology (2019)

Potential conflict of interest: Nothing to report. We thank Rimbaş et al. for their interest in our study,(1) and we appreciate the comments. We agree that left atrial (LA) volume assessment is preferable compared with LA dimension. However, the latter is more readily measurable, was available in all our patients, and provides an accurate estimate of LA size in 94% of the patients.2 We also agree that individual 2‐dimensional (2D) and Doppler signals have modest relations with left ventricular filling pressure (LVFP)3 in patients with preserved systolic function; in particular, early diastolic transmitral and myocardial velocity on tissue Doppler imaging ratio (E/e′) of 14 can correlate with an LVFP ranging from 5 to 30.3 In fact, we never stated that “E/e′ ratio can accurately estimate LVFP,” but it is likely that an increase in both LA dimension and E/e′ correlates with increased LVFP.1 Regarding the third issue, the accuracy of noninvasive assessment of left ventricular (LV) diastolic dysfunction (DD) in patients with cirrhosis is unclear. Algorithms proposed by the American Society of Echocardiography in 2009 and 2016 and by the Rotterdam Thorax Center2 performed differently in patients with cirrhosis, demonstrating wide variability of DD prevalence, independently from the severity of liver disease, and no correlation with prognosis.1 None of these algorithms were developed in patients with cirrhosis, but they have been validated in patients with symptomatic cardiovascular diseases,3 aiming at identifying increased LVFP, a condition that is probably uncommon in asymptomatic patients with cirrhosis with normal LV ejection fraction and central hypovolemia. Table 1 reports some studies assessing the prevalence of DD in patients with cirrhosis. Prevalence varies widely, mostly depending on parameters and cut‐off values assumed to define DD. Hence, extreme caution should be exercised when drawing conclusions concerning the grading of DD in patients with cirrhosis. Table 1 - Prevalence of Diastolic Dysfunction in Patients With Cirrhosis Authors Patients (n) Prevalence of DD (%) Classification or Criteria Used for Diagnosis of DD Parameters Assessed Prognostic Value Cesari M, 2015, Eur J Gastroenterol Hepatol 113 whole cohort 37 ASE/EAE, 2009 LAV; E/A; DT NA 36 without ascites 42 Annular e′ velocity (septal and lateral e′); average E/e′ 31 with responsive ascites 38 46 with refractory ascites 21 Nazar A, 2013, J Hepatol 100 58 ASE/EAE, 2009 LAV; E/A; DT No association with mortality. Annular e′ velocity (septal and lateral e′); average E/e′ Sampaio F, 2014, Eur J Intern Med 109 16 Using annular TDI velocities and LAV LAV; E/A; DT No association with mortality. Annular e′ velocity (septal and lateral e′); average E/e′ Sampaio F, 2013, Liver Int 40 Using E/A, DT, IVRT Ruiz‐del‐Arbol L, 2013, Hepatology 80 whole cohort 46 ASE/EAE, 2009 LAV; E/A; DT E/e′ >10 is associated with increased mortality. 26 without ascites 23 Annular e′ velocity (septal and lateral e′); average E/e′ 18 with ascites and normal PRA 11 36 with ascites and elevated PRA 80 Papastergiou V, 2012, Sci World J 92 60 Gabriel Klein, 2009 E/A, DT, IVRT, LA (cm) NA Merli M, 2016, Liver Int 90 40 ASE/EAE, 2009 LAV; E/A; DT LAVi >35 mL/m2 is associated with increased mortality. Annular e′ velocity (septal and lateral e′); average E/e′ Cesari M, 2017, Hepatology 115 30 ASE/EAE, 2009 LAV; E/A; DT Increased LA dimension and/or E/e′ >10 is associated with increased mortality. 17 ASE/EACVI, 2016 Annular e′ velocity (septal and lateral e′); average E/e′ Karagiannakis DS, 2014, Hepatol Int 45 38 Septal e′ <8 cm/second and lateral e′ <10 cm/second LAV; E/A; DT DD and/or average E/e′ ≥9 is associated with increased mortality. Annular e′ velocity (septal and lateral e′); average E/e′ Abbreviations: ASE/EACVI, American Society of Echocardiography and European Association of Cardiovascular Imaging; ASE/EAE, American Society of Echocardiography and European Association of Echocardiography; DD, diastolic dysfunction; DT, early wave deceleration time; E/A, early and late diastolic velocity ratio; E/e′, early diastolic transmitral and myocardial velocity on tissue Doppler imaging ratio; IVRT, isovolumic relaxation time; LAV, left atrial volume; LAVi, left atrial volume indexed; NA, not assessed; PRA, plasma renin activity; TDI, tissue Doppler imaging. Of interest, single indexes such as LA dimension (>4 cm or 35 mL/m2), E/e′ (>10), early and late diastolic velocity ratio (E/A; ≤1), and more recently, the isovolumetric relaxation time (IVRT)/time from onset of E wave to onset of e′ wave ratio4 have demonstrated a significant prognostic value in cirrhosis and therefore should be reported and used for risk stratification purposes to better identify patients with a worse prognosis, which requires a lower threshold to initiate work‐up for liver transplantation.