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

Signals governing the recruitment of T lineage progenitors to the thymus

T cells are a lymphocyte lineage critical for immune defense from a range of pathogens. T cells uniquely complete the majority of their development outside the bone marrow in a specialized organ, the thymus. As self-renewing progenitors are not found in the thymus, continuous T cell production requires the importation of bone marrow-derived progenitors into the thymus via the blood. Thymic settling is selective, as only a subset of bone marrow progenitors with T lineage potential can enter the thymus from blood. The chemokine receptor CCR9 mediates at least a part of this selectivity, but progenitors deficient for CCR9 still settle the thymus, suggesting the involvement of additional signals. In this work, we have assessed the molecules that underlie unirradiated thymic settling and have also investigated their role following irradiation. We first identified a second chemokine receptor, CCR7, which together with CCR9 recruits circulating progenitors into the unirradiated thymus. The absence of both receptors confers a near-absolute defect on thymic settling under competitive conditions. Acutely after irradiation, however, progenitors lacking both receptors gain efficient access to the thymus. We found that the magnitude of early thymic and peripheral T cell reconstitution after irradiation is directly linked to the number of progenitors that enter the thymus. Yet bone marrow progenitors with thymic settling capacity suffer defective reconstitution following bone marrow transplantation. From these results, we conclude that thymic settling signals are altered briefly by irradiation. Furthermore, the delayed recovery of the T lineage can be attributed in part to the diminished delivery of progenitors to the thymus after bone marrow transplantation

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