SESSION TITLE: Cardiovascular Disease Case Report PostersSESSION TYPE: Case Report PostersPRESENTED ON: 10/19/2022 12:45 pm - 01:45 pmINTRODUCTION: Ibrutinib is a novel bruton tyrosine kinase (BTK) inhibitor used to treat B-cell malignancies. Ibrutinib has cardiotoxic potential, often resulting in new onset atrial fibrillation in its recipients, but bradycardia, sinus pause or arrest are rarely reported.CASE PRESENTATION: A 69-year-old male patient with medical history significant for chronic lymphocytic leukemia (CLL) on chemotherapy with ibrutinib for 1 year, and hypertension controlled on amlodipine presented with complaints of worsening fatigue and tiredness and lightheadedness not associated with any prodrome. The patient denied any chest pain, dyspnea, palpitations, nystagmus, vertigo, seizures, or stroke-like symptoms. Social history was significant for smoking but denied any alcohol or illicit drug use. Physical exam was remarkable for bradycardia. EKG done at that time showed sinus bradycardia with irregular premature atrial complexes. Previous EKGs prior to starting chemotherapy showed baseline regular sinus bradycardia of 55 beats per minute, with stable PR interval. Patient was placed on a Holter monitor for further evaluation. Patient was called into the hospital, 2 weeks later, after noticing a 4-second sinus pause. On further review of Holter monitor, patient was noted to have sinus bradycardia of 40 beats per minute with ventricular ectopy and intermittent episodes of atrial fibrillation with rapid ventricular response. Bloodwork was significant for elevated WBC count of 82,000 / uL consistent with his diagnosis of CLL, but otherwise remaining labs were unremarkable. Echocardiogram revealed normal ventricular function with ejection fraction of 55-60%, without any significant structural abnormalities. CT coronary study was significant for dense calcifications of proximal LAD with 50% stenosis and a total coronary calcium score of 133. Thus, a diagnosis of ibrutinib induced sinus node dysfunction was made and the patient received a dual-chamber permanent pacemaker placement in the electrophysiology lab. EKG done post-procedure showed regular paced rhythm and patient reported significant improvement in energy levels. He was discharged as he remained asymptomatic and hemodynamically stable. He remained symptom-free on follow-up visits.DISCUSSION: Our case is only the third reported instance of ibrutinib induced bradycardia, although the exact mechanism of this adverse effect has not yet been established. In vivo studies on mice sinoatrial node (SAN) myocytes demonstrate that SAN dysfunction and arrhythmogenesis was more profound with ibrutinib compared to more selective BTK inhibitor like acalabrutinib, thus indicating an off-target mechanism playing a role in cardiotoxic effects of the drug.CONCLUSIONS: Through our case, we emphasize the possibility of SAN dysfunction secondary to ibrutinib use and call for further human research to determine the mechanism of cardiotoxic effects of ibrutinib and other BTK inhibitors.Reference #1: Tuomi JM, Bohne LJ, Dorey TW, Jansen HJ, Liu Y, Jones DL, Rose RA. Distinct Effects of Ibrutinib and Acalabrutinib on Mouse Atrial and Sinoatrial Node Electrophysiology and Arrhythmogenesis. J Am Heart Assoc. 2021 Nov 16;10(22):e022369. doi: 10.1161/JAHA.121.022369. Epub 2021 Nov 2. PMID: 34726066; PMCID: PMC8751944.Reference #2: Xu L, Dong Q, Zhang N, Lu K, Tang X. Severe Sinus Bradycardia Associated with Ibrutinib: One Rare Case from China. Am J Med Sci. 2021 Jun;361(6):803-805. doi: 10.1016/j.amjms.2020.11.029. Epub 2020 Nov 26. PMID: 33947585.Reference #3: Mathur K, Saini A, Ellenbogen KA, Shepard RK. Profound Sinoatrial Arrest Associated with Ibrutinib. Case Rep Oncol Med. 2017;2017:7304021. doi: 10.1155/2017/7304021. Epub 2017 Dec 10. PMID: 29375920; PMCID: PMC5742500.DISCLOSURES: No relevant relationships by Tharun BandarupalliNo relevant relationships by Bhavesh GajjarNo relevant relationships by supriya peshinNo relevant relationships by Koushik Sanku SESSION TITLE: Cardiovascular Disease Case Report Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Ibrutinib is a novel bruton tyrosine kinase (BTK) inhibitor used to treat B-cell malignancies. Ibrutinib has cardiotoxic potential, often resulting in new onset atrial fibrillation in its recipients, but bradycardia, sinus pause or arrest are rarely reported. CASE PRESENTATION: A 69-year-old male patient with medical history significant for chronic lymphocytic leukemia (CLL) on chemotherapy with ibrutinib for 1 year, and hypertension controlled on amlodipine presented with complaints of worsening fatigue and tiredness and lightheadedness not associated with any prodrome. The patient denied any chest pain, dyspnea, palpitations, nystagmus, vertigo, seizures, or stroke-like symptoms. Social history was significant for smoking but denied any alcohol or illicit drug use. Physical exam was remarkable for bradycardia. EKG done at that time showed sinus bradycardia with irregular premature atrial complexes. Previous EKGs prior to starting chemotherapy showed baseline regular sinus bradycardia of 55 beats per minute, with stable PR interval. Patient was placed on a Holter monitor for further evaluation. Patient was called into the hospital, 2 weeks later, after noticing a 4-second sinus pause. On further review of Holter monitor, patient was noted to have sinus bradycardia of 40 beats per minute with ventricular ectopy and intermittent episodes of atrial fibrillation with rapid ventricular response. Bloodwork was significant for elevated WBC count of 82,000 / uL consistent with his diagnosis of CLL, but otherwise remaining labs were unremarkable. Echocardiogram revealed normal ventricular function with ejection fraction of 55-60%, without any significant structural abnormalities. CT coronary study was significant for dense calcifications of proximal LAD with 50% stenosis and a total coronary calcium score of 133. Thus, a diagnosis of ibrutinib induced sinus node dysfunction was made and the patient received a dual-chamber permanent pacemaker placement in the electrophysiology lab. EKG done post-procedure showed regular paced rhythm and patient reported significant improvement in energy levels. He was discharged as he remained asymptomatic and hemodynamically stable. He remained symptom-free on follow-up visits. DISCUSSION: Our case is only the third reported instance of ibrutinib induced bradycardia, although the exact mechanism of this adverse effect has not yet been established. In vivo studies on mice sinoatrial node (SAN) myocytes demonstrate that SAN dysfunction and arrhythmogenesis was more profound with ibrutinib compared to more selective BTK inhibitor like acalabrutinib, thus indicating an off-target mechanism playing a role in cardiotoxic effects of the drug. CONCLUSIONS: Through our case, we emphasize the possibility of SAN dysfunction secondary to ibrutinib use and call for further human research to determine the mechanism of cardiotoxic effects of ibrutinib and other BTK inhibitors. Reference #1: Tuomi JM, Bohne LJ, Dorey TW, Jansen HJ, Liu Y, Jones DL, Rose RA. Distinct Effects of Ibrutinib and Acalabrutinib on Mouse Atrial and Sinoatrial Node Electrophysiology and Arrhythmogenesis. J Am Heart Assoc. 2021 Nov 16;10(22):e022369. doi: 10.1161/JAHA.121.022369. Epub 2021 Nov 2. PMID: 34726066; PMCID: PMC8751944. Reference #2: Xu L, Dong Q, Zhang N, Lu K, Tang X. Severe Sinus Bradycardia Associated with Ibrutinib: One Rare Case from China. Am J Med Sci. 2021 Jun;361(6):803-805. doi: 10.1016/j.amjms.2020.11.029. Epub 2020 Nov 26. PMID: 33947585. Reference #3: Mathur K, Saini A, Ellenbogen KA, Shepard RK. Profound Sinoatrial Arrest Associated with Ibrutinib. Case Rep Oncol Med. 2017;2017:7304021. doi: 10.1155/2017/7304021. Epub 2017 Dec 10. PMID: 29375920; PMCID: PMC5742500. DISCLOSURES: No relevant relationships by Tharun Bandarupalli No relevant relationships by Bhavesh Gajjar No relevant relationships by supriya peshin No relevant relationships by Koushik Sanku