Arrhythmia Patterns in Patients on Ibrutinib

Introduction: Ibrutinib, a Bruton's tyrosine kinase inhibitor (TKI) used primarily in the treatment of hematologic malignancies, has been associated with increased incidence of atrial fibrillation (AF), with limited data on its association with other tachyarrhythmias. There are limited reports that comprehensively analyze atrial and ventricular arrhythmia (VA) burden in patients on ibrutinib. We hypothesized that long-term event monitors could reveal a high burden of atrial and VAs in patients on ibrutinib.Methods: A retrospective data analysis at a single center using electronic medical records database search tools and individual chart review was conducted to identify consecutive patients who had event monitors while on ibrutinib therapy.Results: Seventy-two patients were included in the analysis with a mean age of 76.9 ± 9.9 years and 13 patients (18%) had a diagnosis of AF prior to the ibrutinib therapy. During ibrutinib therapy, most common arrhythmias documented were non-AF supraventricular tachycardia (n = 32, 44.4%), AF (n = 32, 44%), and non-sustained ventricular tachycardia (n = 31, 43%). Thirteen (18%) patients had >1% premature atrial contraction burden; 16 (22.2%) patients had >1% premature ventricular contraction burden. In 25% of the patients, ibrutinib was held because of arrhythmias. Overall 8.3% of patients were started on antiarrhythmic drugs during ibrutinib therapy to manage these arrhythmias.Conclusions: In this large dataset of ambulatory cardiac monitors on patients treated with ibrutinib, we report a high prevalence of atrial and VAs, with a high incidence of treatment interruption secondary to arrhythmias and related symptoms. Further research is warranted to optimize strategies to diagnose, monitor, and manage ibrutinib-related arrhythmias.

Temporary cardiointerval organization with varying degrees of acute normobaric hypoxia in a healthy person

The influence of acute normobaric hypoxia (ANH) on the male heart chronotropic effects was studied. Thus, a mild degree of ANH (14.5 % O2, 20 min), causing a decrease in blood oxygenation by 6.3 abs. %, accompanied by an initial (by 5 min) decrease in the RR and QT intervals. The average degree of ANH (12.3% O2) leads to a decrease in blood oxygenation by 19.7 abs. %. At the same time, in inverse relationship to the developing hypoxemia, RR and QT significantly decrease. Corrected values (Pc, PQc, QRSc, QTc) increase during the action period of an average degree of hypoxia, indicating an increase in the proportion of atrial contraction time, atrioventricular conduction of excitation and electrical ventricular systole in the total RR duration, which, apparently, provides optimal systolic heart effect. Key words: human, hypoxia, blood oxygenation, cardiointervals.

Maternal Left Ventricular Diastolic and Systolic Function during Normal Pregnancy in Saint Bernard Dogs

This study aimed to evaluate maternal left ventricular (LV) systo-diastolic function using conventional and TDI echocardiography and included 10 healthy Saint-Bernard pregnant bitches. M-mode, peak transmitral flow velocities during early diastole (E) and atrial contraction (A), aortic and pulmonic flow, myocardial performance index (MPI), TDI studies (peak myocardial velocities during early diastole (E’), atrial contraction (A’) and peak systole (S’)), and blood pressure were measured at 21 to 28 (T1), 40 (T2) and 60 (T3) days of gestation and four to eight weeks postpartum (T4). Cardiac output and heart rate were 20% and 9% higher at T3, respectively, compared to T4 (p < 0.01). Lateral S’ was 36% higher at T3 than at T1 (p < 0.05). Changes in diastolic function were demonstrated by 10% lower E wave and 15% A wave at T1, compared to T4 (p < 0.05). E’ and A’ were 23% and 42% higher at T3 compared to T4 (p < 0.01). Both lateral E/E’ and E’/A’ were 6% and 19% lower at T3 compared to T1 (p < 0.01 and p < 0.05, respectively). At T3, MPI was 51% and 34% lower when compared to T1 or T2 (p < 0.05). The echocardiographic evaluation of maternal cardiac function is important, as structural, and functional changes occur throughout pregnancy.

417 Multi-chamber speckle tracking imaging and diagnostic value of left atrial strain in cardiac amyloidosis

Aims Amyloid deposits in all cardiac chambers, impairing their function. We investigated for the first time if a speckle-tracking echocardiography (STE) analysis extended to all four chambers might hold additive diagnostic value for CA and its subtypes [amyloid transthyretin (ATTR-) and light-chain (AL)-CA]. Methods and results We evaluated 423 consecutive patients undergoing a diagnostic workup for CA in two referral centres from 2015 to 2020. CA was diagnosed in 261 patients (62%; ATTR-CA, n = 144, 34%; AL-CA, n = 117, 28%). Patients with CA had an impaired function of all cardiac chambers, particularly those with ATTR-CA. Peak left atrial longitudinal strain (LA-PALS) was the only STE parameter that predicted CA and ATTR-CA independent of laboratory and standard echocardiographic variables (Model 1). It also predicted ATTR-CA among patients with unexplained hypertrophy regardless of a diagnostic score (IWT score). Patients with either LA-PALS or LA-peak atrial contraction strain (PACS) in the first quartile (LA-PALS &lt;6.65% or LA-PACS &lt;3.62%) had an almost 4-fold higher likelihood of CA and ATTR-CA regardless of Model 1. Among patients with unexplained hypertrophy, those with LA-PALS or LA-PACS in the first quartile had an almost 9-fold higher likelihood of ATTR-CA irrespective of Model 1, and a 2-fold higher likelihood of ATTR-CA beyond the IWT score. Conclusions STE measures of all two chambers are abnormal in patients with CA, particularly in those with ATTR-CA. LA strain holds independent diagnostic significance. Among patients screened for CA, those with LA-PALS &lt;6.65% and/or LA-PACS &lt;3.62% have a high likelihood of CA and ATTR-CA.

Left atrial strain in cardiac amyloidosis

Background Patients with cardiac amyloidosis (CA) display an enlarged and dysfunctional left atrium (LA), because of the effects of left ventricular (LV) diastolic and then systolic dysfunction, as well as the amyloid infiltration of LA wall. A single study reported impaired LA strain in CA, but differences among amyloid light-chain (AL) and transthyretin (ATTR) CA and the correlates of reduced LA strain have not been characterized. Methods We evaluated 426 consecutive patients undergoing a screening for suspected CA in 2 tertiary referral centres. Among them, 262 (61%) were diagnosed with CA (n=117 AL-CA, n=145 ATTR-CA). We measured peak atrial longitudinal strain (PALS) and peak atrial contraction strain (PACS) from 4- and 2-chamber (4C, 2C) views, and correlated them with maximum and minimum LA volumes, E/e' ratio, and LV global longitudinal strain (GLS). Results LA strain was much more severely impaired in patients with ATTR-CA than those without CA, and to a lesser extent than those with AL-CA (Figure). LA volumes were larger in patients with ATTR-CA than those without CA (maximal LA volume, p=0.042; minimal LA volume, p&lt;0.001), and those with AL-CA (both volumes, p&lt;0.001). LA strain values were more closely correlated with minimal than maximal LA volumes, and patients with AL-CA displayed stronger correlations than those with ATTR-CA or without CA; for example, Spearman's rho values for 4C-PALS vs. minimal LA volume were 0.595, 0.481, and 0.462, respectively (all p&lt;0.001). Furthermore, LA strain correlated with E/e' in patients with AL-CA, but not in those with ATTR-CA: 4C-PALS vs. E/e', rho 0.406, p=0.001 (AL-CA), p=0.401 (ATTR-CA), and p=0.097 (no CA). Finally, LA strain correlated most closely with LV GLS in patients with AL-CA: 4C-PALS vs. LV GLS, rho 0.431, p&lt;0.001 (AL-CA), rho 0.401, p&lt;0.001 (ATTR-CA), rho 0.219, p=0.042 (no CA). Conclusions LA volume increase and reduced LA strain is particularly prominent in patients with ATTR-CA. Patients with AL-CA seem to display closer relationships between LA strain, size and haemodynamic load, possibly reflecting the most acute disease course, and lower time for amyloid deposition in the LA wall. FUNDunding Acknowledgement Type of funding sources: None.

Influence of left atrial expansion and decreased interventricular septal wall motion following a weakened atrial kick on brain natriuretic peptide secretion in early-stage heart failure

Background The secretion of brain natriuretic peptide (BNP) by left ventricular (LV) myocytes increases even in patients with normal LV function. Currently, the cause of BNP increase in patients with stages A and B chronic heart failure remains unknown. Purpose To investigate the increase of BNP in early-stage, asymptomatic heart failure. Methods Consecutive patients (N=188; mean age: 68±11 years; body mass index: 23.0±3.9 kg/m2, female/male: 88/100) with heart failure (stages A and B), including non-valvular atrial fibrillation (NVAF), and LV ejection fraction &gt;50% with estimated glomerular filtration rate &gt;30% were recruited in this study. The echocardiographic parameters of LV systolic function (e.g., LV endo-diastolic/endo-systolic volume and ejection fraction) or diastolic markers (e.g., E/A ratio calculated from the trans mitral flow velocity and E/e' ratio), in addition to the data obtained from tissue Doppler images, were evaluated. LA volume was obtained from a three-dimensional heart model. Moreover, LV and left atrial (LA) global longitudinal strains were evaluated. The BNP levels measured within 1 month from echocardiographic examination were compared with the echocardiographic markers, in addition to an estimated glomerular filtration rate. Results BNP was elevated in patients with NVAF (NVAF, median: 63.0 pg/ml [quartile: 33.2–74.7 pg/ml]; non-NVAF, median: 25.6 pg/ml [quartile: 13.5–50.8 pg/ml]; p=0.0015) and patients with stage B heart failure (stage B, median: 41.7 pg/ml [quartile: 21.5–67.5 pg/ml]; stage A, median: 23.4 pg/ml [quartile: 11.7–39.0 pg/ml]; p=2.99E-05). The presence of hypertension and the sex of patients did not lead to significant differences in this population. The LA volume corrected by the body surface area was well correlated with the BNP value (r=0.55; 95% confidence interval [CI]: 0.44–0.64; p=4.42E-16) and age (r=0.51; 95% CI: 0.40–0.61; p=4.64E-14). LA global longitudinal strain (r=−0.42; 95% CI: −0.53 to −0.29; p=3.05E-09) and the velocity of interventricular septum during atrial contraction (r=−0.40; 95% CI: −0.51 to −0.27; p=1.84E-08) were also correlated with BNP elevation. However, the markers of diastolic and systolic function of LV were not correlated with BNP increase in patients with subclinical heart failure. Multivariate analysis revealed that LA volume (β: 0.991; 95% CI: 0.682–1.299; p=1.85E-09), stage B heart failure (β: 0.116; 95% CI: 0.016–0.216; p=0.023), age (β: 0.013; 95% CI: 0.008–0.018; p=6.414E-07), body mass index (β: −0.020; 95% CI: −0.033 to 0.007; p=0.002), and a decrease in the velocity of interventricular septum during atrial contraction (β: −0.048; 95% CI: −0.070 to −0.026; p=2.683E-05) contributed to the increase in BNP. Conclusion LA enlargement with no relation to diastolic function, age, and diminishment of interventricular motion caused by atrial contraction may be sensitive markers of BNP secretion in patients with subclinical stage, asymptomatic heart failure. FUNDunding Acknowledgement Type of funding sources: None.

Prediction model for thyrotoxic atrial fibrillation: a retrospective study

Background Thyrotoxic atrial fibrillation (TAF) is a recognized significant complication of hyperthyroidism. Early identification of the individuals predisposed to TAF would improve thyrotoxic patients’ management. However, to our knowledge, an instrument that establishes an individual risk of the condition is unavailable. Therefore, the aim of this study is to build a TAF prediction model and rank TAF predictors in order of importance using machine learning techniques. Methods In this retrospective study, we have investigated 36 demographic and clinical features for 420 patients with overt hyperthyroidism, 30% of which had TAF. At first, the association of these features with TAF was evaluated by classical statistical methods. Then, we developed several TAF prediction models with eight different machine learning classifiers and compared them by performance metrics. The models included ten features that were selected based on their clinical effectuality and importance for model output. Finally, we ranked TAF predictors, elicited from the optimal final model, by the machine learning tehniques. Results The best performance metrics prediction model was built with the extreme gradient boosting classifier. It had the reasonable accuracy of 84% and AUROC of 0.89 on the test set. The model confirmed such well-known TAF risk factors as age, sex, hyperthyroidism duration, heart rate and some concomitant cardiovascular diseases (arterial hypertension and conjestive heart rate). We also identified premature atrial contraction and premature ventricular contraction as new TAF predictors. The top five TAF predictors, elicited from the model, included (in order of importance) PAC, PVC, hyperthyroidism duration, heart rate during hyperthyroidism and age. Conclusions We developed a machine learning model for TAF prediction. It seems to be the first available analytical tool for TAF risk assessment. In addition, we defined five most important TAF predictors, including premature atrial contraction and premature ventricular contraction as the new ones. These results have contributed to TAF prediction investigation and may serve as a basis for further research focused on TAF prediction improvement and facilitation of thyrotoxic patients’ management.

World Congress of Perinatal Medicine

SPEAKERS ABSTRACT The application of super slow review of ultrasound clips to a diagnosis of fetal tachyarrhythmia Name and surname: Jun Yoshimatsu Institution: National Cerebral and Cardiovascular Center Email: [email protected] Objective Fetal arrhythmias occur in 1–2% of all pregnant cases. Premature atrial contraction (PAC), premature ventricular contraction (PVC) which are clinically benign are relatively common and do not require therapy. In contrast supraventricular tachycardias (SVTs), atrial flutter (AFL), ventricular tachycardia which are life-threatening are relatively rare but require treatment. These tachyarrhythmias easily complicate fetal congestive heart failure which can be followed by a fetal death. Thus, prenatal treatment for SVT and AFL is warranted to convert to sinus rhythm. Recently our group demonstrated that protocol-defined transplacental treatment for fetal SVT and AFL was effective and tolerable in 90% of cases. In order to choose the appropriate medication for fetal tachyarrhythmia the accurate diagnosis is important. Because fetal electrocardiography is still not available fetal echocardiography is commonly used for the diagnosis of fetal arrhythmia. The M-mode and Doppler echocardiography may achieve prenatal identification of arrhythmic types. The easier method helps more accurate and precise diagnosis of it. Recent advances of ultrasound examination technology allows a high spatial resolution and high temporal resolution at the same time. The image editing of video clips of four chamber view, which is the most easier image plane, is applicable for the diagnosis of fetal arrhythmias. We conducted the research to innovate the useful video clip editing method including a super slow motion for the precise diagnosis of fetal arrhythmias. Method From our fetal echocardiography database, 55 fetal echocardiography video clips (35 AFL, 20 SVT) were reviewed. Four chamber view clips of each case were selected. Every clips were edited into 10% speed. One examiner inserted the clip maker at the timing of atrial contraction and ventricular contraction. The intervals between ventricular contraction and atrial contraction were measured. Also the number of times of contraction of atrium and ventricle and their relations were recorded. Results Every contractions of each portion (atrium and ventricle) could be detected easily with edited video clips. The differentiation between AFL and SVT could be done completely by counting the number of contractions of atrium and ventricle. Also the V-A intervals and the A-V intervals could be measured in one hundredth seconds. In all cases, the diagnosis is compatible with that had made postnatally. Conclusion The first step of this study was depended on the examiner’s naked eyes helped by editing application. The accuracy of each steps of this study were satisfactory. This is the preliminary step to conduct the deep learning of Artificial Intelligence (AI). The most important point of using AI is setting up what to teach and how to teach. Our study showed the possibility of the application of AI to make a diagnosis of fetal tachyarrhythmia.