High neutrophil-to-lymphocyte ratio is associated with cancer therapy-related cardiovascular toxicity in high-risk cancer patients under immune checkpoint inhibitor therapy.

BACKGROUND: Cancer therapy-related cardiovascular toxicity (CTR-CVT) from immune checkpoint inhibitor (ICI) therapy is still incompletely characterized, and patients with pre-existing cardiovascular disease represent a particularly high-risk cohort. Valid parameters for risk stratification of these patients are missing. Neutrophil-to-lymphocyte ratio (NLR) has been shown to predict mortality and adverse events in other cardiovascular cohorts. The present study aims to examine the predictive capacity of NLR for risk stratification of patients particularly vulnerable for CTR-CVT under ICI therapy. METHODS: We performed an analysis of 88 cancer patients (69 ± 11 years, 25% female) with pre-existing cardiovascular disease under ICI therapy from the prospective Essen Cardio-Oncology Registry (ECoR). NLR was assessed at patient enrollment and the population was divided through receiver operator characteristic (ROC) curve analysis in patients with low (< 4.57) and high (≥ 4.57) NLR. Endpoint was the whole spectrum of CTR-CVT, according to the European guidelines on cardio-oncology. The median follow-up was 357 days (interquartile range (IQR): 150-509 days). RESULTS: We observed 4 cases of myocarditis, 17 cases of vascular toxicity, 3 cases of arterial hypertension, 22 cases of arrhythmia or QTc prolongation and 17 cases of cardiovascular dysfunction. NLR was associated with overall CTR-CVT by univariable Cox regression (hazard ratio (HR): 1.443; 95% confidence interval (CI) 1.082-1.925; p = 0.013). However, this association was attenuated after adjusting for further confounders. CONCLUSION: NLR is moderately associated with CTR-CVT in cancer patients with pre-existing cardiovascular disease under ICI therapy. Surveillance of NLR during ICI therapy might be an effective and economically biomarker for risk stratification in these high-risk patients.

Right ventricular and atrial strain in patients with advanced melanoma undergoing immune checkpoint inhibitor therapy.

AIMS: While immune checkpoint inhibitor (ICI) therapy significantly improves survival rates in advanced melanoma, ICI can evoke severe immune-related cardiovascular adverse events. Right ventricular (RV) dysfunction negatively impacts the outcomes in cardiovascular diseases and may be an early sign for overall cardiotoxicity. We aimed to assess RV function in melanoma patients undergoing ICI therapy using conventional echocardiographic and strain imaging techniques. METHODS AND RESULTS: We retrospectively examined 30 patients (40% women, age 59 ± 13 years) with advanced melanoma (stage III/IV) before and 4 weeks after the start of ICI therapy (follow-up at 39 ± 15 days); n = 15 of the patients received nivolumab, and n = 15 received the combination therapy nivolumab/ipilimumab. Two-dimensional echocardiography with assessment of RV longitudinal strain of the free wall (RV-LSFW) and assessment of right atrial (RA) strain from speckle tracking was performed at baseline and after the start of ICI therapy. Short-term ICI therapy caused a reduction of RV-LSFW (-25.5 ± 6.4% vs. -22.4 ± 4.3%, P = 0.002) and of RA strain during contraction phase (-10.6 ± 3.5% vs. -7.7 ± 3.1%, P = 0.001). Conventional parameters including tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), and pulmonary artery systolic pressure were not different between the two time points (TAPSE 26 ± 5 vs. 25 ± 5 mm, P = 0.125; FAC 38 ± 13% vs. 38 ± 14%, P = 0.750; and pulmonary artery systolic pressure 27 ± 10 vs. 25 ± 8 mmHg, P = 0.268). CONCLUSIONS: Analysis of RV and RA strain shows alterations even in a short-term follow-up, while changes in RV function are not visible by conventional RV parameters. Alterations in RV and RA strain could be early signs of cardiotoxicity and therefore should be assessed in patients undergoing ICI therapy.