Complete Atrioventricular Block Associated with Pembrolizumab-induced Acute Myocarditis: The Need for Close Cardiac Monitoring

Katsume, Yumi; Isawa, Tsuyoshi; Toi, Yukihiro; Fukuda, Ryo; Kondo, Yasuteru; Sugawara, Shunichi; Ootomo, Tatsushi

doi:10.2169/internalmedicine.0255-17

Cited by 34 publications

(30 citation statements)

References 10 publications

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“…Cardiovascular toxicities are among the rare organ toxicities of ICI therapy [5, 6]. With increased use of ICIs over the past few years, numerous reports of cardiovascular toxicities have emerged (summarized in Table 1, Table 2, Table 3) [7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35]. The most serious among them is the development of fulminant myocarditis, a potentially fatal clinical disease which has been the primary focus for the cardio-oncology community [12].…”

Section: Introductionmentioning

confidence: 99%

Cardiac Toxicity Associated with Immune Checkpoint Inhibitors: Case Series and Review of the Literature

Agrawal¹,

et al. 2019

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The development of immune checkpoint inhibitors (ICIs) has revolutionized the treatment of patients with advanced stage cancers. However, immune-related adverse events are frequently observed. Cardiac toxicity from ICI therapy can range from asymptomatic troponin-I elevations to conduction abnormalities of the heart and even fulminant myocarditis. Although rare, myocarditis is a potentially fatal adverse effect of ICI therapy. We present a series of five cases of ICI-related cardio-toxicity diagnosed and managed at Roswell Park Comprehensive Cancer Center along with a review of published case reports in the literature. Our series highlights the importance of high clinical suspicion, early diagnosis of myocarditis, and prompt initiation of immunosuppressive therapy.

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Section: Introductionmentioning

confidence: 99%

Cardiac Toxicity Associated with Immune Checkpoint Inhibitors: Case Series and Review of the Literature

Agrawal¹,

et al. 2019

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“…However, recently published studies did not find any effects of paclitaxel on cardiac rhythm, which was confirmed by electrocardiography data [24]. Available literature contains a few case reports presenting the cases of complete atrioventricular block development in oncologic patients undergoing chemotherapy, in particular, in a female patient with breast cancer receiving epirubicin and paclitaxel [25] or in a male patient with lung cancer receiving monoclonal antibodies (pembrolizumab) [26].…”

Section: Conflict Of Interestmentioning

confidence: 82%

“…В литературе описаны единичные клинические случаи развития полной атриовентрикулярной блокады у онкологических пациентов, находящихся на химиотерапии, в частности у пациентки с раком молочной железы на фоне приема эпирубицина и паклитаксела [25] или у пациента с раком легкого на фоне приема моноклональных антител (пембролизумаб) [26].…”

Section: Conflict Of Interestunclassified

Heart rhythm and conduction disorders as manifestations of cardiotoxicity of anticancer treatment: myth or reality?

Васюк

Шупенина

Novosel

et al. 2020

SMJ

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АннотацияВ настоящее время онкологические заболевания являются одной из основных причин смертности. Современная противоопухолевая терапия позволяет сохранять жизнь и социальную адаптацию онкологических пациентов в течение многих лет. Однако применение противоопухолевых препаратов ограничено из-за их побочных, в ряде случаев тяжелых кардиотоксических эффектов, таких как ишемическая болезнь сердца (ИБС), токсическая кардиомиопатия, хроническая сердечная недостаточность (ХСН), артериальная гипертензия и др. Нарушения ритма и проводимости встречаются в среднем у 16-36% пациентов, получающих химиопрепараты, а фибрилляция предсердий (ФП) является одним из наиболее частых аритмогенных проявлений кардиотоксичности. Антрациклины, алкилирующие агенты и моноклональные антитела нарушают работу ионных насосов, способствуют избыточному выходу кальция из саркоплазматического ретикулума, изменению потенциала действия, более быстрому развитию спонтанной диастолической деполяризации и в конечном итоге провоцируют развитие ФП. Некоторые химиопрепараты, в частности антрациклины, ингибиторы тирозинкиназ и гистон деацетилазы, нарушают работу калиевых каналов, что приводит к увеличению потенциала действия и удлинению интервала QT. Данные о влиянии других классов химиопрепаратов на проводящую систему сердца немногочисленны и противоречивы. Нарушения ритма и проводимости, вызванные химиотерапией, могут привести к снижению дозы или отмене противоопухолевых препаратов, требуют тщательного мониторирования и совместного подхода врачей нескольких специальностей к ведению этих пациентов. Ключевые слова:кардиотоксичность, фибрилляция предсердий, синдром удлиненного интервала QT, антрациклины, моноклональные антитела, ингибиторы тирозинкиназ. Конфликт интересов:авторы заявляют об отсутствии конфликта интересов. Прозрачность финансовой деятельности:никто из авторов не имеет финансовой заинтересованности в представленных материалах или методах. Для цитирования: Васюк Ю.А., Шупенина Е.Ю., Новосел Е.О., Агапов И.С. Нарушения ритма и проводимости сердца как проявления кардиотоксичности противоопухолевого лечения -миф или реальность? Сибирский медицинский журнал. 2020;35(1):13-21. https://doi. AbstractOncologic diseases are currently one of the leading causes of death. Modern anticancer therapy allows preserving life and social adaptation of cancer patients for many years. However, the use of anticancer drugs is limited due to their adverse and, 13-21 + Elena Y. Shupenina,

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“…Interestingly, similar to the article by Katsume et al, our patient was receiving pembrolizumab after initial prior treatment with pemetrexed and bevacizumab for NSCLC. Katsume et al's patient was also found to have a high PD-L1 expression of >95% and received pembrolizumab at 200 mg 16 days prior to admission [7]. In other words, both patients were highly susceptible to the effects of pembrolizumab with their tumor cells having a high degree of expression (90% or greater), and both patients developed heart block the second time they received the immunotherapy, approximately 3 weeks after the first infusion.…”

Section: Discussionmentioning

confidence: 98%

“…Immune-related cardiotoxicity is a rare but often fatal complication. Cardiotoxicities associated with pembrolizumab include myocarditis, heart failure, sick sinus syndrome, cardiomyopathy, cardiac fibrosis, and cardiac arrest [3][4][5][6][7]. The following case describes a patient who developed complete heart block which appears to be temporally related to the use of the anti-PD-1 antibody, pembrolizumab.…”

Section: Introductionmentioning

confidence: 99%

Pembrolizumab-Induced Mobitz Type 2 Second-Degree Atrioventricular Block

Khan

Riaz

Carhart

2020

Case Reports in Cardiology

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Pembrolizumab is a monoclonal antibody directed towards programmed cell death protein 1 (PD-1) and is an antineoplastic drug which has a growing variety of oncologic uses. Pembrolizumab is commonly associated with immune-related adverse events (IRAEs) but is infrequently noted to cause cardiotoxicities such as myocarditis, arrhythmias, and heart failure. The following case report illustrates the clinical course of a 67-year-old female patient with stage IV non-small-cell lung cancer who developed Mobitz type 2 second-degree atrioventricular block three weeks after receiving her first infusion of pembrolizumab. Within a few hours of presentation, she progressed to symptomatic complete heart block requiring emergent placement of a temporary transvenous pacemaker. The article further discusses proposed mechanisms to explain IRAEs and management of IRAEs. We conclude by recommending a higher degree of caution and awareness among all physicians when treating patients on immunotherapy and a multidisciplinary approach when considering resumption of immune checkpoint inhibitor therapy.

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Complete Atrioventricular Block Associated with Pembrolizumab-induced Acute Myocarditis: The Need for Close Cardiac Monitoring

Cited by 34 publications

References 10 publications

Cardiac Toxicity Associated with Immune Checkpoint Inhibitors: Case Series and Review of the Literature

Cardiac Toxicity Associated with Immune Checkpoint Inhibitors: Case Series and Review of the Literature

Heart rhythm and conduction disorders as manifestations of cardiotoxicity of anticancer treatment: myth or reality?

Pembrolizumab-Induced Mobitz Type 2 Second-Degree Atrioventricular Block

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