Ibrutinib is an irreversible Bruton tyrosine-kinase inhibitor. In prospective studies, the ibrutinib efficacy in the treatment of various B-cell malignancies was established. Different ibrutinib side-effects have been found: diarrhea, arthralgia, infections, neutropenia, hypertension and increased risk of bleeding. Most of the mentioned side-effects were <3rd degree of severity and mostly didn't require dose adjustment or therapy discontinuation. Also, there was an increase in the incidence of atrial fibrillation (AFib) (6-16%). The AFib pathogenesis in this patient population is not clarified, but there are indications that ibrutinib inhibits phosphoinositide-3-kinase (PI3K)-Akt signal-pathway expressed in the myocytes. Regardless of the molecular pathogenesis, the clinical effect of ibrutinib on the myocardium, especially the left atrium, has not been studied. Hence, the aim of this study is to determine the ibrutinib effect on echocardiographic parameters of left atrial function.

This study will be performed as a clinical, prospective, observational cohort study with a structured follow-up period of 12 months. All consecutive patients with hemato-oncologic diseases (including chronic lymphocytic leukemia, Mantle-cell lymphoma, Waldenstrom macroglobulinemia, etc.) prescribed with chronic ibrutinib therapy, who are able to understand and sign informed consent, will be enrolled. Primary objective is change of the left atrial function measured by the decrease of the left atrial strain deformation > 10%.

Recruiting should not exceed 12 months with the minimal follow-up period of 12 months (24 months in total). Standardized statistical methods and tests will be done using SPSS Version 22.0 or newer.

This unique study offers the possibility to show the long-term effect of chronic ibrutinib therapy on left atrial function assessed by transthoracic echocardiography. This observational data is needed to further refine the treatment of these patients and to prevent possible side-effects of ibrutinib which could endanger this specific patient population.

Inclusion Criteria:

• patients with haemato-oncologic diseases (including chronic lymphocytic leukemia, Mantle-cell lymphoma, Waldenstrom macroglobulinaemia, etc.)
• patients prescribed with chronic ibrutinib therapy
• patients who are able to understand and sign informed consent

Exclusion Criteria:

• patients with haemato-oncologic diseases who were prescribed with concomitant chemotherapy which can impact left atrial function
• patients < 18 years old
• patients with known or at initial echocardiography established dilated cardiomyopathy with left ventricular ejection fraction < 35%
• patients with permanent atrial fibrillation and dilated left atrium or dilated both atriums
• patients implanted with cardiac implantable electronic devices
• patients who underwent cardiac surgery
• patients with congenital heart diseases (surgically corrected or not)
• patients with severe valvular pathology
• patients with terminal renal disease
• patients with chronic obstructive pulmonary disease - GOLD grade 4
• patients with life expectancy < 12 months
• patients not willing to undergo clinical follow-up or sign informed consent
• patients recruited in another clinical study

All consecutive patients with haemato-oncologic diseases (including chronic lymphocytic leukemia, Mantle-cell lymphoma, Waldenstrom macroglobulinaemia) prescribed with chronic ibrutinib therapy, who are able to understand and sign informed consent, will be enrolled.