Global Circumferential and Radial Strain Among Patients With Immune Checkpoint Inhibitor Myocarditis

Quinaglia, Thiago; Góngora, Carlos; Awadalla, Magid; Hassan, M; Zafar, Amna; Drobni, Zsófia; Mahmood, Syed; Zhang, Lili; Coelho‐Filho, Otávio R.; Suero-Abreu, Giselle Alexandra; Rizvi, Muhammad A.; Sahni, Gagan; Mandawat, Anant; Zataraín-Nicolás, Eduardo; Mahmoudi, Michael; Sullivan, Ryan J.; Ganatra, Sarju; Heinzerling, Lucie; Thuny, Franck; Éderhy, Stéphane; Gilman, Hannah; Sama, Supraja; Nikolaidou, Sofia; Mansilla, Ana González; Calles, Antonio; Cabral, Marcella; Fernández‐Avilés, Francisco; Gavira, Juán José; González, Nahikari Salterain; Castro, Manuel García de Yébenes; Barac, Ana; Afilalo, Jonathan; Zlotoff, Daniel A.; Zubiri, Leyre; Reynolds, Kerry L.; Devereux, Richard B.; Hung, Judy; Picard, Michael H.; Yang, Eric H.; Gupta, Dipti; Michel, Caroline; Lyon, Alexander R.; Chen, Carol L.; Nohria, Anju; Fradley, Michael G.; Thavendiranathan, Paaladinesh; Neilan, Tomas G.

doi:10.1016/j.jcmg.2022.06.014

Cited by 11 publications

(5 citation statements)

References 37 publications

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“…To determine the role of GLS, global circumferential strain (GCS), and global radial strain (GRS) in ICI-treated patients, Quinaglia et al conducted a retrospective study in which 75 patients with ICI myocarditis were compared with 50 ICI-treated patients without myocarditis [46]. They found that GLS, GCS, and GRS can predict CV events with better accuracy than LVEF, hs-TnT, and age, in patients who were diagnosed with ICI-induced myocarditis.…”

Section: Discussionmentioning

confidence: 99%

Extensive CArdioVAscular Characterization and Follow-Up of Patients Receiving Immune Checkpoint Inhibitors: A Prospective Multicenter Study

et al. 2023

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Background: The increasing use of immune checkpoint inhibitors (ICIs) in the treatment of both advanced and early stages of various malignancies has resulted in a substantial increase in the incidence of cardiovascular (CV) immune-related adverse events (irAEs). The current follow-up guidelines are based on anecdotal evidence and expert opinions, due to a lack of solid data and prospective studies. As many questions remain unanswered, cardiac monitoring, in patients receiving ICIs, is not always implemented by oncologists. Hence, an urgent need to investigate the possible short- and long-term CV effects of ICIs, as ICI approval is continuing to expand to the (neo)adjuvant setting. Methods: We have initiated a prospective, multicenter study, i.e., the CAVACI trial, in which a minimum of 276 patients with a solid tumor, eligible for ICI treatment, will be enrolled. The study consists of routine investigations of blood parameters (troponin and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, in particular) and a thorough CV follow-up (electrocardiograms, transthoracic echocardiograms, and coronary calcium scoring) at fixed time points for a total period of two years. The primary endpoint is the cumulative incidence of troponin elevation in the first three months of ICI treatment, compared to baseline levels. Furthermore, secondary endpoints include incidence above the upper limit of normal of both troponin and NT-proBNP levels, evolution in troponin and NT-proBNP levels, the incidence of CV abnormalities/major adverse cardiac events, evaluation of associations between patient characteristics/biochemical parameters and CV events, transthoracic echocardiography parameters, electrocardiography parameters, and progression of coronary atherosclerosis. Recruitment of patients started in January 2022. Enrolment is ongoing in AZ Maria Middelares, Antwerp University Hospital, AZ Sint-Vincentius Deinze, and AZ Sint-Elisabeth Zottegem. Trial registration: ClinicalTrials.gov Identifier: NCT05699915, registered 26 January 2023.

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Section: Discussionmentioning

confidence: 99%

Extensive CArdioVAscular Characterization and Follow-Up of Patients Receiving Immune Checkpoint Inhibitors: A Prospective Multicenter Study

et al. 2023

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“…While reduced left ventricular systolic function and regional wall motion abnormalities (RWMA) on the echocardiogram can occur, a normal left ventricular ejection fraction (LVEF) has been demonstrated in more than 50% of patients with confirmed ICImyocarditis, indicating that the presence of normal LVEF cannot exclude the diagnosis (18). In a retrospective analysis (19) including 140 patients with ICI-myocarditis, the presence of decreased global longitudinal strain (GLS) was a predictor of MACE regardless of LVEF (19); similar findings have been reported using global radial and circumferential strain (20). Finally, in a surveillance study among 129 patients who received ICIs, a decline in GLS correlated with elevation in high sensitivity (hs) cTnI suggesting that GLS is associated with myocyte injury (21).…”

Section: Echocardiographymentioning

confidence: 68%

Circulating biomarkers in the diagnosis and prognosis of immune checkpoint inhibitor-related myocarditis: time for a risk-based approach

Murtagh,

deFilippi,

Zhao

et al. 2024

Front. Cardiovasc. Med.

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Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that block immune checkpoints and therefore activate immune cells, allowing them to recognize and attack cancer cells. ICIs have revolutionized oncology practice, but their use has been complicated by immune-related adverse events (irAEs). Of cardiovascular (CV) irAEs, ICI-related myocarditis has received significant attention due to high mortality rates, ranging from 25% to 50%, despite its overall low incidence. Establishing the early diagnosis of ICI-myocarditis is important for early initiation of steroids and consideration of hospitalization in patients who are at risk for hemodynamic compromise and need high acuity care in a tertiary setting. In this review, we summarize the diagnostic and prognostic tools for ICI-myocarditis, including electrocardiography, echocardiography, cardiac magnetic resonance imaging, with emphasis on circulating biomarkers. Cardiac troponins (cTns) are an essential component of the diagnosis of ICI-myocarditis, and we provide a summary of the recent studies that utilized different assays (cTnI vs. cTnT) and outcomes (diagnosis vs. prognosis including major adverse cardiac outcomes). With the exponential increase in ICI use across different oncology indications, there is a major need to include biomarkers in risk stratification to guide diagnosis and treatment. Our review proposes a framework for future multisite registries, including cTn evaluation at baseline and at the time of irAE suspicion, with development of central biobanking to allow head-to-head evaluation and clinical validation of different biomarker assays in ICI-myocarditis. This approach, with the inclusion of CV biomarkers into clinical and pragmatic oncology trials, holds promise to improve the early recognition and management of ICI-myocarditis and CV irAEs, thus leading to better outcomes.

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“…Myocardial strain has been proposed as an early marker for ICI myocarditis, and is associated with elevated troponin levels [ 15 ]. It has also been suggested as a predictor of mortality [ 16 , 17 ]. Although our numbers are small in the present study, we observe that despite high sensitivity, GLS did not have significant prognostic value.…”

Section: Discussionmentioning

confidence: 99%

Complete heart block is a significant predictor of mortality in immune checkpoint inhibitor myocarditis

O’Shea,

Karikalan,

Yusuf

et al. 2023

Cardio-Oncology

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Background Immune checkpoint inhibitor (ICI) myocarditis is associated with significant mortality risk. Electrocardiogram (ECG) changes in ICI myocarditis have strong prognostic value. However the impact of complete heart block (CHB) is not well defined. This study sought to evaluate the impact of CHB on mortality in ICI myocarditis, and to identify clinical predictors of mortality and CHB incidence. Methods We conducted a retrospective cohort study of patients with ICI myocarditis at three Mayo Clinic sites from 1st January 2010 to 31st September 2022 to evaluate mortality rates at 180 days. Clinical, laboratory, ECG, echocardiographic, and cardiac magnetic resonance imaging (CMR) characteristics were assessed. Cox and logistic regression were performed for associations with mortality and CHB respectively. Results Of 34 identified cases of ICI myocarditis, 7 (20.6%) had CHB. CHB was associated with higher mortality (HR 7.41, p = 0.03, attributable fraction 86.5%). Among those with CHB, troponin T (TnT) < 1000 ng/dL, low white blood cell count and high ventricular rate at admission were protective. There was trend towards increased survival among patients who underwent permanent pacemaker insertion (p = 0.051), although most experienced device lead complications. Factors associated with development of CHB included prolonged PR and QRS intervals and low Sokolow Lyon Index. Where these were normal and TnT was < 1000 ng/dL, no deaths occurred. Impaired myocardial longitudinal strain was sensitive for ICI myocarditis but was not prognostically significant. Conclusion There is a strong temporal association between CHB and early mortality in people with ICI myocarditis. Focusing on arrhythmogenic complications can be helpful in predicting outcomes for this group of critically ill individuals.

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Global Circumferential and Radial Strain Among Patients With Immune Checkpoint Inhibitor Myocarditis

Cited by 11 publications

References 37 publications

Extensive CArdioVAscular Characterization and Follow-Up of Patients Receiving Immune Checkpoint Inhibitors: A Prospective Multicenter Study

Extensive CArdioVAscular Characterization and Follow-Up of Patients Receiving Immune Checkpoint Inhibitors: A Prospective Multicenter Study

Circulating biomarkers in the diagnosis and prognosis of immune checkpoint inhibitor-related myocarditis: time for a risk-based approach

Complete heart block is a significant predictor of mortality in immune checkpoint inhibitor myocarditis

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