Evaluation of Ibrutinib Cardiotoxicity By Comparative Use of Speckle-Tracking Technique and Biomarkers.

BACKGROUND: Ibrutinib, a relatively new antineoplastic agent, has multiple cardiovascular effects that are still insufficiently known and evaluated, including subclinical myocardial damage. STUDY QUESTION: The present study aims to assess the role of the myocardial strain, alone and in combination with cardiac biomarkers, in the early detection of ibrutinib-induced cardiotoxicity. STUDY DESIGN: We included 31 outpatients with normal left ventricular ejection fraction (LVEF) on ibrutinib, in a tertiary University Hospital between 2019 and 2020, and evaluated them at inclusion and after 3 months. MEASURES AND OUTCOMES: Data on myocardial strain, cardiac biomarkers [high-sensitive troponin T (hs TnT) and N-terminal probrain natriuretic peptide (NT-proBNP)], and ambulatory electrocardiographic monitoring were collected. RESULTS: Myocardial deformation decreased significantly (P < 0.001) at later evaluation and hs TnT and NT-proBNP increased significantly (P = 0.019 and P = 0.03, respectively). The increase in hs TnT correlated with the increase in the left ventricle global longitudinal strain (LVGLS); in other words, it correlated with the decrease in myocardial deformation. No association was found between LVGLS increase and the increase in NT-proBNP. LVGLS modification was not significantly influenced by age, anemia, or arrhythmia burden quantified by 24-hour Holter monitoring (P = 0.747, P = 0.072, respectively; P = 0.812). LVEF did not change significantly during follow-up. CONCLUSIONS: In patients on ibrutinib, evaluation of myocardial strain is useful in identifying early cardiac drug toxicity, surpassing the sensitivity and specificity limits of LVEF. In these patients, concomitant assessment of hs TnT increases the predictive power for subclinical myocardial involvement.

Ibrutinib in patients with atrial fibrillation - the challenge of thromboembolic prophylaxis.

Ibrutinib is a novel drug used in haematological malignancies. Its use is associated with an increased risk of atrial fibrillation (AF), which, in turn, exposes patients to embolic risk, including stroke. Reducing this risk requires anticoagulant therapy which is a matter of concern in the context of the increased bleeding risk of patients with haematological malignancies. In this context the presence of thrombocytopenia related to haematological disorder, ibrutinib-anticoagulants and ibrutinib-platelets interactions contribute to the amplification of the problem. The correct assessment of the thrombosis vs. haemorrhage balance represents a significant challenge for the clinician. In this paper we discuss practical issues related to anticoagulation in patients treated with ibrutinib and incident AF.

Role of signal-averaged electrocardiography and ventricular late potentials in patients with chronic obstructive pulmonary disease.

Patients with chronic obstructive pulmonary disease (COPD) have an increased risk for cardiac arrhythmias. Ventricular late potentials (VLP) on signal-averaged electrocardiography (SAECG) are associated with an increased risk for malignant ventricular arrhythmias. Our aim is to investigate the modifications of SAECG parameters and the presence of VLP as possible indicators of proarrhythmic substrate in patients with COPD. We prospectively enrolled 41 consecutive patients in the COPD group and 63 patients without any history of pulmonary disease, matched for age and hypertension history, in the control group. Pulmonary function tests, arterial blood gases, echocardiography, 24-hour Holter monitoring and SAECG were performed. We measured total filtered QRS duration (QRSf), duration of high frequency, low-amplitude signals < 40 V (HFLA40), and root mean square voltage in the last 40 ms (RMS40). VLP were considered if at least two of these parameters were abnormal. Results. We did not register any significant differences in QRSf, HFLA40 or RMS40 between the two groups. In the COPD group there was a non-significant higher percentage of patients with VLP in comparison with the control group. In the COPD patients we registered a significantly higher number of isolated premature ventricular beats and of combined complex ventricular arrhythmias, consisting of polymorphic PVC, couplets, triplets or nonsustained ventricular tachycardias. None of these arrhythmic parameters correlated with SAECG variables or with the presence of VLP. Conclusion. In COPD patients parameters measured on signal-averaged electrocardiography and ventricular late potentials analysis have little value in risk stratification for ventricular arrhythmias.

P Wave Signal-Averaged Electrocardiography in Patients with Chronic Obstructive Pulmonary Disease.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is associated with higher incidence of supraventricular arrhythmias. Atrial late potentials (ALP) detected by P-wave signal-averaged electrocardiography (SAECG) could be useful in detecting the patients at risk for supraventricular arrhythmias. Our objective was to assess the role of P-wave SAECG and ALP detection for arrhythmic risk evaluation of the patients with exacerbated COPD. METHODS: We prospectively included 45 patients with exacerbation of COPD and 58 age- matched patients with no history of pulmonary disease in a control group. We performed pulmonary function tests, arterial blood gases, echocardiography, 24-hour Holter monitoring and P-wave SAECG. We measured filtered P-wave duration (FPD), the root mean square (RMS) voltages in the last 40, 30 and 20 ms of the filtered P-wave (RMS 40, RMS 30 and RMS 20), the root mean square voltage of the filtered P-wave potentials (RMS-p), and the integral of the potentials during the filtered P-wave (Integral-p). ALP was defined as FPD > 132 ms and RMS 20 < 2.3 µV. RESULTS: Isolated atrial premature beats (APB) and supraventricular tachycardias (SVT) were more frequent in the COPD group. There were no significant differences between groups regarding the P wave SAECG parameters. In the COPD group none of the supraventricular arrhythmias was correlated with ALP or any P-wave SAECG parameters. CONCLUSIONS: The patients with acute exacerbation of COPD but no apparent cardiac disease have a higher incidence of supraventricular arrhythmias. P-wave SAECG analysis and ALP detection have little value in the arrhythmic risk evaluation of these patients.