Lenvatinib for the treatment of hepatocellular carcinoma-a real-world multicenter Australian cohort study.

INTRODUCTION: Hepatocellular carcinoma (HCC) is a serious complication of chronic liver disease. Lenvatinib is an oral multikinase inhibitor registered to treat advanced HCC. This study evaluates the real-world experience with lenvatinib in Australia. METHODS: We conducted a retrospective cohort study of patients treated with lenvatinib for advanced HCC between July 2018 and November 2020 at 11 Australian tertiary care hospitals. Baseline demographic data, tumor characteristics, lenvatinib dosing, adverse events (AEs) and clinical outcomes were collected. Overall survival (OS) was the primary outcome. Progression free survival (PFS) and AEs were secondary outcomes. RESULTS: A total of 155 patients were included and were predominantly male (90.7%) with a median age of 65 years (interquartile range [IQR]: 59-75). The main causes of chronic liver disease were hepatitis C infection (40.0%) and alcohol-related liver disease (34.2). Median OS and PFS were 7.7 (95% confidence interval [CI]: 5.8-14.0) and 5.3 months (95% CI: 2.8-9.2) respectively. Multivariate predictors of mortality were the need for dose reduction due to AEs (Hazard ratio [HR] 0.41, p < 0.01), new or worsening hypertension (HR 0.42, p < 0.01), diarrhoea (HR 0.47, p = 0.04) and more advanced BCLC stage (HR 2.50, p = 0.04). Multivariable predictors of disease progression were higher Child-Pugh score (HR 1.25, p = 0.04), the need for a dose reduction (HR 0.45, p < 0.01) and age (HR 0.96, p < 0.001). AEs occurred in 83.9% of patients with most being mild (71.6%). CONCLUSIONS: Lenvatinib remains safe and effective in real-world use. Treatment emergent diarrhoea and hypertension, and the need for dose reduction appear to predict better OS.

Incremental Value of ePLAR-The Echocardiographic Pulmonary to Left Atrial Ratio in the Assessment of Sub-Massive Pulmonary Emboli.

BACKGROUND: Acute pulmonary embolism (PE) is characterized hemodynamically by abrupt obstruction in trans-pulmonary blood flow. The echocardiographic Pulmonary to Left Atrial ratio (ePLAR, tricuspid regurgitation Vmax/mitral E/e') has been validated as a non-invasive surrogate for trans-pulmonary gradient (TPG) that accurately differentiates pre-capillary from post-capillary chronic pulmonary hypertension. This study assessed ePLAR as an incremental echocardiographic assessment tool compared with traditional measures of right ventricular pressure and function. METHODS: In total, 110 (57.4 ± 17.6 years) patients with confirmed sub-massive pulmonary emboli with contemporaneous echocardiograms (0.3 ± 0.9 days) were compared with 110 age-matched controls (AMC). RESULTS: Tricuspid velocities were higher than AMC (2.6 ± 0.6 m/s vs. 2.4 ± 0.3 m/s, p < 0.05), although still consistent with "normal" right ventricular systolic pressures (34.2 ± 13.5 mmHg vs. 25 ± 5.3 mmHg, p < 0.05) with lower mitral E/e' values (8.2 ± 3.8 vs. 10.8 ± 5.1, p < 0.05). ePLAR values were higher than AMC (0.36 ± 0.14 m/s vs. 0.26 ± 0.10, p < 0.05) suggesting significantly elevated TPG. Detection of abnormal echocardiographic findings increased from 29% (TRVmax ≥ 2.9 m/s) and 32% (reduced tricuspid annular plane systolic excursion) to 70% with ePLAR ≥ 0.3 m/s. CONCLUSIONS: Raised ePLAR values in acute sub-massive pulmonary embolism suggest elevated trans-pulmonary gradients even in the absence of acutely increased pulmonary artery pressures. ePLAR dramatically increases the sensitivity of echocardiography for detection of hemodynamic perturbations in sub-massive pulmonary embolism patients, which may offer clinical utility in diagnosis and management.

The Prognostic Value of the Diastolic Stress Test in Patients Undergoing Treadmill Stress Echocardiography.

BACKGROUND: Exercise stress echocardiography (SE) is well validated for the evaluation of myocardial ischemia. Diastolic stress testing (DST) is recommended in the 2016 American Society of Echocardiography and European Association of Cardiovascular Imaging Guidelines for unexplained dyspnea. This study's aim was to prognostically evaluate the DST prospectively in a large stress testing population. METHODS: Patients underwent SE with mitral E/e' measured before and after maximal treadmill exertion to estimate diastolic function. Patients were divided into four groups: group 1 (n = 201)-ischemic; group 2 (n = 1,563)-negative DST (E/e'pre < 12, E/e'post < 12); group 3 (n = 68)-positive DST (E/e'pre < 12, E/e'post ≥ 12); group 4 (n = 314)-high baseline E/e' (E/e'pre ≥ 12). RESULTS: Consecutive patients (n = 2,201, 770 [35%] female; 58 ± 12 years) were followed after SE for 27,964 patient-months. Time to first heart failure event (composite of heart failure admission, worsening New York Heart Association class, worsening ejection fraction, or cardiovascular death) was analyzed and adjusted using Cox proportional hazards regression. Ischemic patients hazard ratio (HR) was 28, 95% CI, 17-44, P < .0005, for subsequent heart failure compared with negative DST patients. Nonischemic, positive DSTs were highly predictive (HR = 4.2; 95% CI, 1.6-11.0; P = .001); while high E/e'pre was not predictive (HR = 1.3; 95% CI, 0.7-2.4; P = .49) of future heart failure events. CONCLUSIONS: DST differentiates heart failure prognosis in patients with induced diastolic dysfunction. Ischemia predictably portends the worst heart failure outcomes, and nonischemic, positive diastolic stress tests predicted more events compared with negative tests. These prognostic data support and add to the recommendations of the 2016 guidelines.