P696Incidence of sinus node dysfunction with cancer chemotherapy: a systematic review of literature
Authors: Alugubelli N , Kanwal A , Allamneni R , Schamp D J , Meininger G R , Saini A 
Published: October 2019

Abstract

Background
Introduction of newer classes of chemotherapeutic agents has led to improved survival in many cancers, often at the cost of increased side effects. With the advent of cardio-oncology, there has been growing focus on cardiac side effects of chemotherapy like cardiomyopathy, QT prolongation, VT and AF. However, data on cancer chemotherapy related sinus node dysfunction (SND) is limited.

Objective
To assess the incidence of chemotherapy related SND through a systematic review of available literature.

Methods
We performed a systematic review of PUBMED database for studies reporting SND (including sinus bradycardia, sinus pauses, sinoatrial exit blocks or asystole) with use of chemotherapeutic agents. Weighted average incidence of SND was calculated from studies. Case reports were reported independently.

Results
2012 articles were reviewed of which 38 were eligible for data extraction. Incidence of SND varied significantly between drug classes. However, specific drugs were associated with increased incidence of SND like anthracyclines (Epirubicin 8.3%), antimetabolites (5 Fluorouracil 20%), tyrosine kinase inhibitors (crizotinib 43%), antimicrotubule agents (paclitaxel 29%) and angiogenesis inhibitors (Thalidomide 22%). The weighted average incidence is shown in table.
Drug type Drug Type of cancers No. of studies Total No. Weighted average of incidence of sinus arrhythmias No. of case reports Anthracyclines Epirubicin Breast, Hodgkin's disease 1 24 8.3% 1 Idarubicin CML – – – 1 Unclassified anthracyclines Ewing sarcoma 2 370 4.31% – Antimetabolites 5 Fluorouracil Esophageal, gastric, colon, rectal 1 5 20% 1 Capecitabine Rectal cancer – – – 1 Methotrexate Osteosarcoma – – – 1 Cytarabine AML – – – 1 Antimicrotubule agent Paclitaxel Ovarian cancer 2 4505 29.36% – Kinase inhibitors Crizotinib Lung 2 1095 43% 4 Alectinib Lung 1 225 5% – Ibrutinib Mantle cell lymphoma – – – 1 Monoclonal antibodies Infliximab Ulcerative colitis – – – 1 Angiogenesis inhibitors Thalidomide Multiple myeloma 4 83 21.62% 2 Endostar Metastatic colorectal and gastric 1 23 13% – Selective estrogen modulators Tamoxifene Extracranial meningioma – – – 1 Antiandrogen Abiraterone Prostate cancer 1 17 6% – Other drugs Crisnatol mesylate Advanced solid tumors 1 43 2.3% – Mitoxantrone AML – – – 1 Combination drugs Bevacizumab +Vorinostat Malignant Glioma 1 40 3% – All-trans-retinoic acid+idarubicin AML – – – 2 Tivantinib+Erlotinib Advanced solid malignancies 1 32 23.1% – Paclitaxel+Carboplatin+Bevacizumab Lung – – – 1 Paclitaxel+Carboplatin Ovarian 1 79 2.9% – Daunorubicin+Amsacrine AML – – – 1 CHOP Diffuse large B cell lymphoma – – – 1

Conclusion
There is cumulative evidence of increased incidence of SND with certain chemotherapeutics. In pre-existing SND, certain drugs and combinations must be avoided and alternative agents, should be considered. Future studies are needed to evaluate the role of remote cardiac monitoring and permanent pacing in specific situations where no safer alternatives exist.