Newly diagnosed cardiovascular disease in patients treated with immune checkpoint inhibitors: a retrospective analysis of patients at an academic tertiary care center

Abstract

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 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 to 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 in a real-world clinical setting.

Immune Checkpoint Inhibitors—Associated Cardiotoxicity

“…In this study, major adverse cardiac events, defined as a composite of cardiovascular death, nonfatal infarction, nonfatal stroke, and hospitalization for heart failure, occurred in 13.3% of patients during a median follow-up of 6 months with a median time to event of 51 days [ 32 ]. In another one-institution study of 424 cancer patients who received any ICI treatment from 2011 to 2017, 14.6% developed cardiovascular diseases after initiation of ICI treatment, defined as a new ICD diagnosis code for cardiomyopathy, heart failure, arrhythmia, heart block, pericardial disease, or myocarditis [ 33 ]. Similar to our study, the most frequently diagnosed cardiac condition was arrhythmia (6.1%) and 5.4% of patients had newly diagnosed heart failure [ 33 ].…”

“…In another one-institution study of 424 cancer patients who received any ICI treatment from 2011 to 2017, 14.6% developed cardiovascular diseases after initiation of ICI treatment, defined as a new ICD diagnosis code for cardiomyopathy, heart failure, arrhythmia, heart block, pericardial disease, or myocarditis [ 33 ]. Similar to our study, the most frequently diagnosed cardiac condition was arrhythmia (6.1%) and 5.4% of patients had newly diagnosed heart failure [ 33 ]. However, the aforementioned studies used data of earlier years (mostly from 2017, [ 22 , 31 , 33 ]), from a single institution [ 32 , 33 ], or focusing on one or two cancer sites [ 22 , 31 , 32 ].…”

Predicting cardiac adverse events in patients receiving immune checkpoint inhibitors: a machine learning approach

“…For example, Waheed et al reported 15% of ICI patient developed new cardiac disease: 0.4% developed cardiomyopathy; 5% developed heart failure; 6% developed an arrhythmia; 2% developed pericardiac disease; 2% developed heart block; and 0.2% developed myocarditis. 59 It is possible that pre-existing atrial fibrillation/heart failure is being routinely documented by a patient's oncologist, even if the patient is not experiencing new disease. To address this concern, we did not count ICD/MedDRA codes as cardiac events if similar codes were already part of the patient's medical history.…”

The Diagnosis and Management of Immune Checkpoint Inhibitor Cardiovascular Toxicity: Myocarditis and Beyond

“…Cardiovascular disease was diagnosed within a median of 63 days after the initiation of ICI treatment. Mortality in ICI-treated patients with a concomitant diagnosis of incident cardiovascular disease was higher, compared to those without (66% vs. 41.4%, odds ratio of 2.77) [12].…”

“…As in the cases of suspected non-ICI-related myocarditis, levels of cardiac biomarkers, including troponin and brain natriuretic peptide (BNP) levels, should be measured. In one series, more than 90% of patients had elevated troponin while over 60% had elevated BNP [12]. Patients with major adverse cardiac events (MACEs) had significantly higher troponin levels than those without, demonstrating the prognostic importance of biomarkers in this setting.…”