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.