Early subclinical myocardial, vascular and endothelial dysfunction in cancer patients treated with immune checkpoint inhibitors

Background Immune checkpoint inhibitors (ICIs) have significantly improved cancer outcomes; however, immune-mediated cardiovascular toxicity is increasingly recognized. Data on early subclinical myocardial, vascular and microvascular effects of ICIs remains limited. Purpose To evaluate early changes in myocardial deformation, arterial stiffness, endothelial glycocalyx integrity and coronary microvascular function in patients receiving ICIs. Methods Adult cancer patients initiating ICI therapy were prospectively enrolled. Comprehensive cardiovascular assessment was performed at baseline and at 6-month follow-up and included: i) global left ventricular longitudinal strain (GLS) by speckle-tracking imaging, ii) myocardial global work efficiency (GWE) by left ventricular longitudinal strain - noninvasive brachial artery pressure loops, iii) carotid femoral pulse wave velocity (PWV) and central systolic blood pressure (Complior ALAM), iv) coronary flow reserve (CFR) by Doppler echocardiography, v) perfused boundary region (PBR) of the sublingual arterial microvessels, with increasing PBR indicating reduced endothelial glycocalyx thickness (Microscan, Glycocheck), Results Thirty-six patients (mean age 65 years, 58% male) were included. Most patients were treated with PD-1 inhibitors (69%), while 31% received PD-L1 inhibitors. Lung cancer was the most frequent malignancy (39%), followed by gastrointestinal (19%), renal (17%), and other malignancies. Left ventricular ejection fraction remained preserved during follow-up (56.3±5.1% vs 55.7±5.4%, p=0.07). In contrast, GLS deteriorated significantly (from −18.4±2.9% to −16.6±2.8%, p<0.01), accompanied by a reduction in myocardial GWE (from 94.4±2.3% to 92.5±2.7%, p<0.01). Arterial stiffness worsened (PWV increased from 12.2±2.1 to 12.8±2.2 m/s, p=0.008), and coronary microvascular function declined, with CFR decreasing from 2.48±0.27 to 2.35±0.26 (p<0.01). Endothelial glycocalyx integrity deteriorated (PBR increased from 2.17±0.29 to 2.25±0.30, p=0.005). During one-year follow-up, six non-cardiovascular deaths, one pulmonary embolism, one immune-related myositis and one myocardial infarction were recorded. Conclusion ICI therapy is associated with early subclinical myocardial deformation impairment, arterial stiffening, endothelial glycocalyx impairment and coronary microvascular dysfunction, despite preserved ejection fraction. These findings support systematic cardiovascular surveillance and prevention in patients receiving immune checkpoint inhibitors.