Background Ibrutinib is a Bruton’s tyrosine kinase inhibitor used in the treatment of hematological malignancies. The most common cardiotoxicity associated with ibrutinib is atrial arrhythmia (atrial fibrillation and flutter). It is known that patients with cardiovascular disease (CVD) are at an increased risk for developing atrial arrhythmia. However, the rate of atrial arrhythmia in patients with pre-existing CVD treated with ibrutinib is unknown. Objective This study examined whether patients with pre-existing CVD are at a higher risk for developing atrial arrhythmias compared to those without prior CVD. Methods A single-institution retrospective chart review of patients with no prior history of atrial arrhythmia treated with ibrutinib from 2012 to 2020 was performed. Patients were grouped into two cohorts: those with CVD (known history of coronary artery disease, heart failure, pulmonary hypertension, at least moderate valvular heart disease, or device implantation) and those without CVD. The primary outcome was incidence of atrial arrhythmia, and the secondary outcomes were all-cause mortality, risk of bleeding, and discontinuation of ibrutinib. The predictors of atrial arrhythmia (namely atrial fibrillation) were assessed using logistic regression. A Cox-Proportional Hazard model was created for mortality. Results Patients were followed for a median of 1.1 years. Among 217 patients treated with ibrutinib, the rate of new-onset atrial arrhythmia was nearly threefold higher in the cohort with CVD compared to the cohort without CVD (17% vs 7%, p = 0.02). Patients with CVD also demonstrated increased adjusted all-cause mortality (OR 1.9, 95% CI 1.06-3.41, p = 0.01) and decreased survival probability (43% vs 54%, p = 0.04) compared to those without CVD over the follow-up period. There were no differences in risk of bleeding or discontinuation between the two cohorts. Conclusions Pre-existing cardiovascular disease was associated with significantly higher rates of atrial arrhythmia and mortality in patients with hematological malignancies managed with ibrutinib.

Acute kidney injury is a reversible medical condition commonly caused by nephrotoxic agents. The infrequency that a nebulized medication elicits a renal insult presents a rare diagnostic challenge. Within this case, we report a 57-year-old cystic fibrosis patient with chronic kidney disease (CKD) Stage G3b (baseline 1.5–1.6 mg/dL) who developed an acute kidney injury (AKI) with a serum creatinine elevation to 4.08 mg/dL and associated worsening vestibular dysfunction related to twice-daily nebulized tobramycin inhalation solution (TIS). The patient was found to have a tobramycin serum level of 4.2 μg/mL 2.5 h after TIS dosing, with elevation remaining present at 1.1 μg/mL 24 h after discontinuation of therapy. Laboratory values at one month continued to show elevated creatinine levels at 2.1 mg/dL, suggesting progression of his baseline CKD. This case supports the benefit of obtaining tobramycin serum levels and vestibular/audiology function testing when evaluating patients on chronic nebulized TIS who present with acute or chronic renal dysfunction. From these serum levels, adjustments to daily dosing, regular monitoring of tobramycin serum levels, or discontinuation of treatment should be made to prevent permanent renal damage in patients with CKD. Calculated Naranjo ADR Probability Scale: 9; Definite.

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Introduction: Device related thrombosis (DRT) is an indication for continuation of anticoagulation for patients undergoing left atrial appendage (LAA) occlusion. There is a paucity of data in regards to the definition of DRT on coronary CT angiography (CTA) in patients with WATCHMAN FLX TM (Boston scientific) device implantation. Methods: This is a single center experience of using CTA for follow up in patients post WATCHMAN FLX TM implantation. 37 consecutive patients who underwent WATCHMAN FLX TM implantation at our center and had CTA performed at first follow up were included. CTA images were analyzed for the presence of hypo-attenuated thickening (HAT) on the device, device positioning, peridevice gap, angulation, compression percentage, depth of implant from coumadin ridge and enhancement in the LAA compared to left atrium (LA). Results: Among 37 patients with CTA follow up, HAT was noted in 28 patients (75%). 38% of these patients had HAT >3 mm. LAA patency (LAA/LA ratio of >25%) was seen in 7 patients (10%), 4 with gaps around the device and the rest secondary to trans-fabric leak. Gap around the device was noted in 13 patients (35%). 6 of these 13 patients had >4 mm gap; 5/6 patients had HAT and 3/6 patients had >25% enhancement in the LAA compared to LA. Increased compression % on both CTA and intraprocedural TEE was associated with absence of HAT (p=0.0003) as well as better sealing on CTA (LAA/LA ratio of >25%) (p=0.04). 6 months follow up is available on only 18 patients; only one of these patients had stoke and that patient did not have HAT on the CT scan. Conclusions: Definition of thrombus on WATCHMAN FLX TM device is not clearly defined on CTA. HAT on CTA could be artifact from the device knob and gutter or visible endothelialization around the device. Further studies with multimodality imaging and clinical correlation are needed to help determine normal cut offs for HAT on these CTAs.

Background:Ibrutinib is a Bruton's tyrosine kinase inhibitor used in the treatment of hematological malignancies. The most common cardiotoxicity associated with ibrutinib is atrial arrhythmia (atrial brillation and utter). It is known that patients with cardiovascular disease (CVD) are at an increased risk for developing atrial arrhythmia. However, the rate of atrial arrhythmia in patients with pre-existing CVD treated with ibrutinib is unknown. Objective:This study examined whether patients with pre-existing CVD are at a higher risk for developing atrial arrhythmias compared to those without prior CVD. Methods:A single-institution retrospective chart review of patients with no prior history of atrial arrhythmia treated with ibrutinib from 2012 to 2020 was performed. Patients were grouped into two cohorts: those with CVD (known history of coronary artery disease, heart failure, pulmonary hypertension, at least moderate valvular heart disease, or device implantation) and those without CVD. The primary outcome was incidence of atrial arrhythmia, and the secondary outcomes were all-cause mortality, risk of bleeding, and discontinuation of ibrutinib. Results:Patients were followed for a median of 1.1 years. Among 217 patients treated with ibrutinib, the rate of new-onset atrial arrhythmia was nearly threefold higher in the cohort with CVD compared to the cohort without CVD (17% vs 7%, p = 0.02). Patients with CVD also demonstrated increased adjusted all-cause mortality (OR 1.9, 95% CI 1.06-3.41, p = 0.01) and decreased survival probability (43% vs 54%, p = 0.04) compared to those without CVD over the follow-up period. Conclusions:Pre-existing cardiovascular disease was associated with signi cantly higher rates of atrial arrhythmia and mortality in patients with hematological malignancies managed with ibrutinib.