Liver cirrhosis (LC) is an important cause of mortality. Access to liver transplantation (LT) has significantly improved the prognosis of LC. A rigorous pre-transplant cardiac evaluation is mandatory, since cardiac dysfunction is considered the main cause of mortality after LT. Notwithstanding, the most updated pre-LT evaluation guidelines provide only an algorithm for the evaluation of major cardiovascular diseases, with no specific recommendations concerning cirrhotic cardiomyopathy (CCM), which is linked to various complications in LC, especially the development of heart failure after invasive procedures and surgical interventions, including LT. CCM is characterized by a cardiac dysfunction that includes systolic and/or diastolic dysfunction and/or electrophysiological abnormalities, in the absence of other known cardiac diseases. The role of the novel methods, tissue Doppler imaging and speckle tracking echocardiography, might be essential in the early detection of cardiac dysfunction, with prognosis implications in LC. All these new methods were only recently included in the CCM diagnosis algorithm. This review summarizes the old and novel techniques used for the diagnosis of CCM, with their diagnosis and prognostic role. It also highlights the strengths and the weaknesses of the new provided CCM diagnostic consensus, and proposes a step-by- step novel diagnostic algorithm, in order to better detect cardiac dysfunction.cirrhotic cardiomyopathy

Funding Acknowledgements “This work was supported by a grant of Ministery of Research and Innovation, CNCS-UEFISCDI, project number PN-III-P1-1-TE-2016-0669, within PNCDI III” Background Differentiation between heart failure with preserved ejection fraction (HFpEF) and isolated diastolic dysfunction (DD) at rest is crucial, since the prognosis is different. Symptoms are often non-specific, while NTproBNP might not be available. Increased NTproBNP is predicted by none of the currently used transthoracic echocardiographic (TTE) parameters. However, assessment of left atrial (LA) function by speckle tracking echocardiography (STE) might be a potential new marker of increased LV filling pressure. Aim. To assess LA function by STE in HFpEF and DD, on top of the currently used TTE parameters, in order to establish the added value of LA deformation in the diagnosis of HFpEF. Methods 70 patients were enrolled prospectively: 40 with HFpEF (68 ± 9 yrs) and 30 with DD (60 ± 10 yrs). TTE was used to assess LV ejection fraction (LVEF), E/E’ ratio, left atrial volume index (LAVi), and systolic pulmonary arterial pressure (sPAP). STE was used to assess LA functions: reservoir function by strain from MVC to MVO (LASr) and positive strain rate (LASRr), conduit function by strain from MVO to onset of atrial contraction (LAScd) and early negative strain rate during conduit phase (LASRcd), and LA pump function by negative strain at MVC (LASct) and late negative strain rate during atrial contraction phase (LASRct). NTproBNP was measured in all patients. Results HFpEF patients had significantly higher LVEF, NTproBNP, E/E’ ratio, and sPAP, but similar LAVi compared to DD, suggesting higher LV filling pressure (Table). LA reservoir and conduit function were similar. However, LA pump function was significantly lower in HFpEF, expressed by LASRct (Tabel). NTproBNP correlated with E/E’ ratio, sPAP, and LASRct (all r = 0.44, p < 0.001), but not with LAVi. By multiple regression analysis, best predictor for NTproBNP > 125pg/ml was LASRct (r = 0.60, r2 =0.30, p < 0.001). LASRct < -1.29 (AUC = 0.82, sensitivity 75%, specificity 81%) was the only predictor of NTproBNP > 125pg/ml (Figure). Conclusion LA pump function is the only predictor of NTproBNP > 125pg/ml. This parameter should be incorporated in the current protocols for the diagnosis of HFpEF. Group (N) NTproBNP ng/ml LVEF (%) E/E’ sPAP (mmHg) LAVi (ml/m2) LASr (%) LASRr LAScd (%) LASRcd LASRct HFpEF (40) 329 ± 383 62 ± 6 10.4 ± 2.7 34 ± 11 40 ± 9 25 ± 4 1.28 ± 0.3 11.6 ± 5.5 -1.37 ± 0.5 -1.07 ± 0.6 DD (30) 37 ± 26 57 ± 8 7.5 ± 1.8 23 ± 7 39 ± 11 26 ± 6 1.26 ± 0.3 11.2 ± 3.6 -1.5 ± 0.6 -1.76 ± 0.7 P value 0.001 0.008 <0.001 <0.001 0.7 0.4 0.8 0.7 0.4 <0.001 Abstract 409 Figure.

Background Patients with heart failure with reduced ejection fraction (HFrEF) are at high risk for mortality and morbidity. Left atrial volumes (LAVs), measured by 2-dimensional echocardiography (2DE), have been suggested as possible prognostic markers. However, LAVs measured by 2DE are prone to errors due to geometric assumptions and increased variability, whereas 3-dimensional echocardiography (3DE) has been proved to be a more accurate and reproducible method for volume assessment. Purpose To assess the comparative prognostic value of LAVs, measured by 2DE and 3DE, in patients with ischemic and non-ischemic HFrEF, on best clinical care. Methods 135 consecutive patients (59 ± 15 years, 91 males), diagnosed with HFrEF, in sinus rhythm, were assessed by 2DE and 3DE, including full-volume multi-beat acquisitions of the LA and left ventricle (LV). Maximal and minimal indexed LAVs were measured from the 2DE datasets using biplane area-length formula (2D_LAVmax and 2D_LAVmin); and from the 3DE datasets using a dedicated software package (3D_LAVmax and 3D_LAVmin). Patients were followed for 23 ± 14 months after the index event. Primary outcome was cardiac death (CD); secondary outcomes were: 1) HF hospitalization (HFH); 2) a composite cardiac events (CE) end-point, of cardiac death or hospitalization for heart failure, myocardial infarction, coronary revascularization, arrhythmias, or cardiac resynchronization therapy. Results 26 CD, 32 HFH, and 48 CE occurred during follow-up. 2DE and 3DE measurements are in the table. LAVs measured by 2DE did not correlate with outcome. However, 3D_LAVmax and 3D_LAVmin correlated with CD (r = 0.40 and r = 0.38) and CE (r = 0.30 and r = 0.29), all p < 0.05, but not with HFH. By multivariate linear regression analysis, only 3D_LAVmax and 3D_LAVmin were independent predictors for CD and CE, in patients with HFrEF (r²=0.30 and r²=0.32; p < 0.01). Conclusion In patients with HFrEF, LA volumes measured by 3DE, but not by 2DE, were independent predictors for cardiac death and events. However, even LA volumes by 3DE did not have predictive value for future HF rehospitalizations. Echo features for patients with HFrEF 3D end-diastolic LV volume (ml/m2) 101 ± 32 3D end-systolic LV volume (ml/m2) 71 ± 29 3D LV ejection fraction (%) 30 ± 8 2D_LAVmax (ml/m2) 52 ± 18 2D_LAVmin (ml/m²) 31 ± 15 3D_LAVmax (ml/m2) 43 ± 18 3D_LAVmin (ml/m2) 29 ± 16