Results:
Among 66 patients who had echocardiograms prior to ibrutinib initiation, 22 developed AF (33.3%). Patients were followed for a mean 2.8 years. Forty-three patients were male (65.2%) and 23 were female (34.8%). The mean patient age at the time of ibrutinib initiation was 68 years. Patients who developed IRAF were significantly older at the time of ibrutinib initiation (74.1 years vs. 65.1 years, p = 0.002). Mean ibrutinib dose was 428.5mg, and patients who developed IRAF received significantly lower doses of ibrutinib (388.2mg vs. 448.6mg, p = 0.025). Approximately half (53.0%) of patients were being treated for CLL/SLL, whereas 28.8% of patients had other lymphomas (including mantle cell lymphoma, diffuse large B cell lymphoma, follicular lymphoma and MALT lymphoma) and 16.7% had a plasma cell dyscrasia (Waldenstrom’s macroglobulinemia, multiple myeloma, or MGUS). Notably, the baseline rate of HF for this population was higher than the general population at 15.2%, though rates of HF were not significantly different between patients with and without IRAF (27.3% for patients with IRAF, 9.1% for patients without IRAF, p = 0.052). Among 10 patients who had a history of HF and developed IRAF, 6 patients had preserved ejection fraction and 4 patients had a reduced ejection fraction. Sixty-one patients (92.4%) had EKGs prior to initiation of ibrutinib, and 9 of these had left atrial enlargement (LAE) by EKG. The presence of LAE on EKG was not significantly associated with development of AF. Additional baseline characteristics of the patient population are shown in Table 1 .
Among the 22 patients who developed IRAF, only 6 were placed on anticoagulation (27.3%) and 4 (18.2%) were placed on antiplatelet therapy. Two patients (9.1%) were on both anticoagulation and antiplatelet therapy. Twenty patients (90.9%) had paroxysmal AF, and two patients (9.1%) had persistent AF. Both patients with persistent AF were on anticoagulation. In most cases, anticoagulation was deferred given a low CHA2DS2-VASc score or a single, self-limited event of AF. Eleven patients with AF (50%) were symptomatic at the time of AF detection. No patients with AF developed ischemic or embolic strokes during follow up. One patient developed an intraparenchymal hemorrhage, and was diagnosed with new-onset AF at the time of presentation for intraparenchymal hemorrhage. This patient had not been on anticoagulation or antiplatelet therapy previously, and had a CHA2DS2-VASc score of 3.
Baseline echocardiographic parameters were obtained prior to initiation of ibrutinib. LAVI was higher in patients who developed IRAF, though not statistically significant (32.2 vs. 27.1, p = 0.07). E/e’ was significantly higher among patients who developed IRAF (11.5 vs. 9.3, p = 0.04). Left ventricular EF was not significantly different between patient groups (62.7% vs. 61.7%, p = 0.63). Additional baseline echocardiographic measures, including right atrial pressure, TR Vmax, TAPSE, right ventricular size, right ventricular fractional area change, right ventricular systolic pressure, E velocity, A velocity and LV GLS were not significantly different between patient groups, as seen inTable 2 .
Mean PALS was 34.2% ± 9.0 across all patients. Mean PACS was 17.3% ± 5.2, and mean conduit strain was 17.1% ± 6.8. PALS was significantly lower in patients who developed IRAF (30.3% vs. 36.3%, p = 0.01). PACS was lower in patients who developed AF, though this did not reach statistical significance (15.6% vs. 18.2%, p = 0.06). Conduit strain was lower among patients who developed IRAF, though not statistically significant (15.0% vs. 18.3%, p = 0.07). Results comparing PALS, PACS and conduit strain are shown in Table 3 . Intra-observer ICC was 0.86 (95% CI 0.72-0.93) and inter-observer ICC was 0.90 (95% CI 0.80-0.95) for measures of LA strain.