Global Longitudinal Strain and Cardiac Events in Patients With Immune Checkpoint Inhibitor-Related Myocarditis

Awadalla, Magid; Mahmood, Syed; Groarke, John D.; Hassan, M; Nohria, Anju; Rokicki, Adam; Murphy, Sean; Mercaldo, Nathaniel D.; Zhang, Lili; Zlotoff, Daniel A.; Reynolds, Kerry L.; Alvi, Raza M.; Banerji, Dahlia; Liu, Shiying; Heinzerling, Lucie; Jones‐O'Connor, Maeve; Bakar, Rula Bany; Cohen, Justine V.; Kirchberger, Michael C.; Sullivan, Ryan J.; Gupta, Dipti; Mulligan, Connor P.; Shah, Sachin; Ganatra, Sarju; Rizvi, Muhammad A.; Sahni, Gagan; Tocchetti, Carlo G.; Lawrence, Donald P.; Mahmoudi, Michael; Devereux, Richard B.; Forrestal, Brian J.; Mandawat, Anant; Lyon, Alexander R.; Chen, Carol L.; Barac, Ana; Hung, Judy; Thavendiranathan, Paaladinesh; Picard, Michael H.; Thuny, Franck; Éderhy, Stéphane; Fradley, Michael G.; Neilan, Tomas G.

doi:10.1016/j.jacc.2019.11.049

Cited by 208 publications

(170 citation statements)

References 39 publications

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“…86 Confirmation of the diagnosis can be challenging because neither magnetic resonance imaging nor endomyocardial biopsy is sufficiently sensitive, and a diagnosis is often made based on the overall clinical picture (in keeping with proposed consensus definitions). 37,87,88 As SARS-CoV-2 can directly infect the myocardium, with a resultant inflammatory response, SARS-CoV-2 should be considered in the differential diagnosis of a patient with concern for ICI-associated myocarditis. 13,14 There are no data to suggest caution for the continued use of ICIs during this COVID-19 pandemic, especially considering the dramatic cancer responses and overall safety profiles that have been reported with these therapies in previously recalcitrant cancer conditions.…”

Section: Immune Checkpoint Inhibitorsmentioning

confidence: 99%

Cardio‐oncology care in the era of the coronavirus disease 2019 (COVID‐19) pandemic: An International Cardio‐Oncology Society (ICOS) statement

Lenihan

Carver

Porter

et al. 2020

CA A Cancer J Clinicians

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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has given rise to a pandemic of unprecedented proportions in the modern era because of its highly contagious nature and impact on human health and society: coronavirus disease 2019 (COVID-19). Patients with cardiovascular (CV) risk factors and established CV disease (CVD) are among those initially identified at the highest risk for serious complications, including death. Subsequent studies have pointed out that patients with cancer are also at high risk for a critical disease course. Therefore, the most vulnerable patients are seemingly those with both cancer and CVD, and a careful, unified approach in the evaluation and management of this patient population is especially needed in times of the COVID-19 pandemic. This review provides an overview of the unique implications of the viral outbreak for the field of cardiooncology and outlines key modifications in the approach to this ever-increasing patient population. These modifications include a shift toward greater utilization of cardiac biomarkers and a more focused CV imaging approach in the broader context of modifications to typical practice pathways. The goal of this strategic adjustment is to minimize the risk of SARS-CoV-2 infection (or other future viral outbreaks) while not becoming negligent of CVD and its important impact on the overall outcomes of patients who are being treated for cancer.

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Section: Immune Checkpoint Inhibitorsmentioning

confidence: 99%

Cardio‐oncology care in the era of the coronavirus disease 2019 (COVID‐19) pandemic: An International Cardio‐Oncology Society (ICOS) statement

Lenihan

Carver

Porter

et al. 2020

CA A Cancer J Clinicians

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“…One of the most exciting developments in cancer treatment is immunotherapy, which activates the immune system of patients to attack malignancies. 30 Among the immunotherapy armamentarium are ICIs, which have shown promising results. 31 In parallel with the increased use, the recognition of irAEs has also improved.…”

Section: Discussionmentioning

confidence: 99%

PD-1 inhibitor inducing exosomal miR-34a-5p expression mediates the cross talk between cardiomyocyte and macrophage in immune checkpoint inhibitor–related cardiac dysfunction

Xia

Chen

et al. 2020

J Immunother Cancer

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BackgroundImmune checkpoint inhibitors (ICIs) have been an important therapeutic advancement in the field of cancer medicine. Recent reports provided greater insights into the cardiovascular adverse events, which prohibited the use of ICIs. Cardiovascular adverse events occur in different forms, such as myocarditis and cardiomyopathy, myocardial fibrosis, heart failure and pericardial disease. Cardiac aging overlapped with the occurrence of some cardiac diseases. Exosomes mediate cell–cell cross talk in cardiac diseases by transferring a variety of biomolecules, including microRNAs (miRs). miR-34a-5p is a well-known miR associated with the cardiac senescence. This study aimed to investigate whether cardiovascular adverse effects of the programmed cell death 1 (PD-1) inhibitor, a widely used ICI, were related to exosomal-transferred miR-34a-5p in cardiac senescence in a mouse model.Methods and resultsThe upregulation of miR-34a-5p in cardiomyocytes induced by exosomes derived from PD-1 inhibitor–treated macrophages, accompanied by cardiac senescence, caused cardiac injury in mouse hearts. miR-34a-5p was identified as an exosomal transfer RNA to induce cardiac senescence–related injury. Inhibiting miR-34a-5p in macrophages attenuated the exosomePD-1 inhibitor-induced pro-senescent effect in cardiomyocytes. TargetScan and luciferase assay showed that miR-34a-5p targeted the serine/threonine-protein phosphatase 1 regulatory subunit 10 (PNUTS) 3′-untranslated region.ConclusionsExosomes derived from PD-1 inhibitor–treated macrophages exerted a pro-senescent effect by modulating the miR-34a-5p/PNUTS signaling pathway. The findings might supply new targets to ameliorate cardiac injury in patients with cancer receiving PD-1 inhibitor treatment.

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“…This small dataset is congruent with the ndings from Awadalla et al, who demonstrated GLS decreases were lower in patients with ICI induced myocarditis compared to control patients and was associated with the development of major adverse cardiovascular events. 29 Several studies have suggested a potential role for the early initiation of cardioprotective medications including beta blockers and angiotensin system inhibitors to prevent the development of cardiotoxicity associated with anthracyclines and trastuzumab. [30][31][32] There is limited data regarding their bene ts in the setting of ICI-induced cardiotoxicities.…”

Section: Discussionmentioning

confidence: 99%

Cardiotoxicity associated with immune checkpoint inhibitors: A retrospective analysis of patients at an academic tertiary care center

Waheed

Fradley

DeRemer

et al. 2020

Preprint

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Background Immune checkpoint inhibitors (ICIs) are a novel class of anticancer agents that have demonstrated clinical response for both solid and hematological malignancies. ICIs are associated with development of immune-related adverse events including cardiotoxicity. We estimated the incidence of newly diagnosed cardiovascular disease ICI-related cardiotoxicity in patients treated with ICIs at a large, tertiary care center. Methods All patients with a cancer diagnosis who received any ICI treatment in the University of Florida’s Integrated Data Repository from 2011-2017 were included. Cardiovascular disease was defined as a new ICD diagnosis code for cardiomyopathy, heart failure, arrhythmia, heart block, pericardial disease, or myocarditis after initiation of ICI treatment. Results Of 102,701 patients with a diagnosis of malignancy, 424 patients received at least one ICI. Sixty-two (14.6%) patients were diagnosed with at least one new cardiovascular disease after initiation of ICI therapy. Of the 374 patients receiving one ICI, 21 (5.6%) developed heart failure. Of the 49 patients who received two ICIs sequentially, three (6.1%) developed heart failure and/or cardiomyopathy. Incident cardiovascular disease was diagnosed at a median of 63 days after initial ICI exposure. One patient developed myocarditis 28 days after receiving nivolumab. Mortality in ICI treated patients with a concomitant diagnosis of incident cardiovascular disease was higher compared to those who did not (66.1% vs. 41.4%, odds ratio = 2.77, 1.55-4.95, p = 0.0006). Conclusions This study suggests a high incidence of newly diagnosed cardiovascular disease after the initiation of ICI therapy.

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Global Longitudinal Strain and Cardiac Events in Patients With Immune Checkpoint Inhibitor-Related Myocarditis

Cited by 208 publications

References 39 publications

Cardio‐oncology care in the era of the coronavirus disease 2019 (COVID‐19) pandemic: An International Cardio‐Oncology Society (ICOS) statement

Cardio‐oncology care in the era of the coronavirus disease 2019 (COVID‐19) pandemic: An International Cardio‐Oncology Society (ICOS) statement

PD-1 inhibitor inducing exosomal miR-34a-5p expression mediates the cross talk between cardiomyocyte and macrophage in immune checkpoint inhibitor–related cardiac dysfunction

Cardiotoxicity associated with immune checkpoint inhibitors: A retrospective analysis of patients at an academic tertiary care center

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