Electrocardiographic features of immune checkpoint inhibitor associated myocarditis.

BACKGROUND: Myocarditis is a highly morbid complication of immune checkpoint inhibitor (ICI) use that remains inadequately characterized. The QRS duration and the QTc interval are standardized electrocardiographic measures that are prolonged in other cardiac conditions; however, there are no data on their utility in ICI myocarditis. METHODS: From an international registry, ECG parameters were compared between 140 myocarditis cases and 179 controls across multiple time points (pre-ICI, on ICI prior to myocarditis, and at the time of myocarditis). The association between ECG values and major adverse cardiac events (MACE) was also tested. RESULTS: Both the QRS duration and QTc interval were similar between cases and controls prior to myocarditis. When compared with controls on an ICI (93±19 ms) or to baseline prior to myocarditis (97±19 ms), the QRS duration prolonged with myocarditis (110±22 ms, p CONCLUSIONS: The QRS duration is increased in ICI myocarditis and is associated with increased MACE risk. Use of this widely available ECG parameter may aid in ICI myocarditis diagnosis and risk-stratification

Pericardial disease in patients treated with immune checkpoint inhibitors

Background There are limited data on the occurrence, associations and outcomes of pericardial effusions and pericarditis on or after treatment with immune checkpoint inhibitors (ICIs).Methods This was a retrospective study at a single academic center that compared 2842 consecutive patients who received ICIs with 2699 age- and cancer-type matched patients with metastatic disease who did not receive ICI. A pericardial event was defined as a composite outcome of pericarditis and new or worsening moderate or large pericardial effusion. The endpoints were obtained through chart review and were blindly adjudicated. To identify risk factors associated with a pericardial event, we compared patients who developed an event on an ICI with patients treated with an ICI who did not develop a pericardial event. Cox proportional-hazard model and logistical regression analysis were performed to study the association between ICI use and pericardial disease as well as pericardial disease and mortality. An additional 6-week landmark analysis was performed to account for lead-time bias.Results There were 42 pericardial events in the patients treated with ICI (n=2842) over 193 days (IQR: 64–411), yielding an incidence rate of 1.57 events per 100 person-years. There was a more than fourfold increase in risk of pericarditis or a pericardial effusion among patients on an ICI compared with controls not treated with ICI after adjusting for potential confounders (HR 4.37, 95% CI 2.09 to 9.14, p<0.001). Patients who developed pericardial disease while on an ICI had a trend for increased all-cause mortality compared with patients who did not develop a pericardial event (HR 1.53, 95% CI 0.99 to 2.36, p=0.05). When comparing those who developed pericardial disease after ICI treatment with those who did not, a higher dose of corticosteroid pre-ICI (>0.7 mg/kg prednisone) was associated with increased risk of pericardial disease (HR 2.56, 95% CI 1.00 to 6.57, p=0.049).Conclusions ICI use was associated with an increased risk of development of pericardial disease among patients with cancer and a pericardial event on an ICI was associated with a trend towards increase in mortality

Impact of immune checkpoint inhibitors on atherosclerosis progression in patients with lung cancer

Background Patients with lung cancer face a heightened risk of atherosclerosis-related cardiovascular events. Despite the strong scientific rationale, there is currently a lack of clinical evidence examining the impact of immune checkpoint inhibitors (ICIs) on the advancement of atherosclerosis in patients with lung cancer. The objective of our study was to investigate whether there is a correlation between ICIs and the accelerated progression of atherosclerosis among individuals with lung cancer.Methods In this case–control (2:1 matched by age and gender) study, total, non-calcified, and calcified plaque volumes were measured in the thoracic aorta using sequential contrast-enhanced chest CT scans. Univariate and multivariate rank-based estimation regression models were developed to estimate the effect of ICI therapy on plaque progression in 40 cases (ICI) and 20 controls (non-ICI).Results The patients had a median age of 66 years (IQR: 58–69), with 50% of them being women. At baseline, there were no significant differences in plaque volumes between the groups, and their cardiovascular risk profiles were similar. However, the annual progression rate for non-calcified plaque volume was 7 times higher in the ICI group compared with the controls (11.2% vs 1.6% per year, p=0.001). Conversely, the controls showed a greater progression in calcified plaque volume compared with the ICI group (25% vs 2% per year, p=0.017). In a multivariate model that considered cardiovascular risk factors, the use of an ICI was associated with a more substantial progression of non-calcified plaque volume. Additionally, individuals treated with combination ICI therapy exhibited greater plaque progression.Conclusions ICI therapy was associated with more non-calcified plaque progression. These findings underscore the importance of conducting studies aimed at identifying the underlying mechanisms responsible for plaque advancement in patients undergoing ICI treatment.Trial registration number NCT04430712

Serial measurement of global longitudinal strain among women with breast cancer treated with proton radiation therapy : a prospective trial for 70 patients

Purpose: Conventional photon radiation therapy (RT) for breast cancer is associated with a reduction in global longitudinal strain (GLS) and an increase in troponin, N-terminal pro hormone B-type natriuretic peptide (NT-proBNP), and incident heart failure. The cardiac radiation exposure with proton-RT is much reduced and thus may be associated with less cardiotoxicity. The objective was to test the effect of proton-RT on GLS, troponin, and NT-proBNP. Methods and Materials: We conducted a prospective, observational, single-center study of 70 women being treated with proton-RT for breast cancer. Serial measurements of GLS, high-sensitivity troponin I, and NT-proBNP were performed at prespecified intervals (before proton-RT, 4 weeks after completion of proton-RT, and again at 2 months after proton-RT). Results: The mean age of the patients was 46 ± 11 years, and the mean body mass index was 25.6 ± 5.2 kg/m2; 32% of patients had hypertension, and the mean radiation doses to the heart and the left ventricle (LV) were 0.44 Gy and 0.12 Gy, respectively. There was no change in left ventricular ejection fraction (65 ± 5 vs 66 ± 5 vs 64 ± 4%; P = .15), global GLS (–21.7 ± 2.7 vs –22.7 ± 2.3 vs –22.8 ± 2.1%; P = .24), or segmental GLS from before to after proton-RT. Similarly, there was no change in either high-sensitivity troponin or NT-proBNP with proton-RT. However, in a post hoc subset analysis, women with hypertension had a greater decrease in GLS after proton-RT compared with women without hypertension (–21.3 ± 3.5 vs –24.0 ± 2.4%; P = .006). Conclusions: Proton-RT did not affect LV function and was not associated with an increase in biomarkers. These data support the potential cardiac benefits of proton-RT compared with conventional RT