Myocardial deformation, myocardial work and vascular biomarkers for the assessement of patients treated with immune checkpoint inhibitors

Background

Immune checkpoint inhibitors (ICIs) have markedly enhanced cancer treatment outcomes; however, they are increasingly associated with immune-related cardiovascular adverse effects. Evidence regarding their early impact on myocardial, vascular, and microvascular function remains limited.

Objective

To investigate early alterations in myocardial performance, arterial stiffness, endothelial glycocalyx integrity, and coronary microvascular function in patients undergoing ICI therapy.

Methods

Adult cancer patients initiating ICI therapy were prospectively enrolled. Assessment was performed at baseline and at 6-month follow-up and included: (i) left ventricular ejection fraction (LVEF); (ii) global left ventricular longitudinal strain (GLS) by speckle-tracking imaging; (iii) myocardial global work efficiency (GWE) by left ventricular longitudinal strain-noninvasive brachial artery pressure loops; (iv) carotid femoral pulse wave velocity (PWV) and central systolic blood pressure (cSBP; Complior ALAM); (v) perfused boundary region (PBR) of sublingual arterial microvessels (increased PBR indicates reduced endothelial glycocalyx thickness; Microscan, Glycocheck); (vi) coronary flow reserve (CFR) by Doppler echocardiography;

Results

Forty patients (mean age, 68,4 years, 60% male) were included. Most patients were treated with PD-1 inhibitors (80%), while 20% received PD-L1 inhibitors.

Immunotherapy was administered predominantly in the neo-adjuvant setting (65%). Lung cancer was the most frequent malignancy (39%), followed by gastrointestinal (19%), renal (17%), and other malignancies. At 6 months (Table), LVEF remained preserved (56.3±4.4% vs 55.7±4.4%, p=0.07). In contrast, GLS deteriorated significantly (from −18.2±3.1% to −16.4±2.9%, p<0.01), accompanied by a reduction in myocardial work efficiency (from 93.6±5.0% to 91.8±5.1%, p<0.01). Arterial stiffness increased (PWV, from 12.1±3.4 to 12.6±3.5 m/s, p=0.03), and endothelial glycocalyx integrity deteriorated (PBR increasing from 2.18±0.30 to 2.27±0.30, p=0.003). Coronary microvascular function declined, with CFR decreasing from 2.46±0.24 to 2.33±0.28 (p<0.01). During the 6 months, one pulmonary embolism and one immune-related myositis were recorded, with no deaths.

Conclusion

Treatment with ICIs is linked to early, subclinical alterations in myocardial deformation, increased arterial stiffness, disruption of endothelial glycocalyx integrity, and impairment of coronary microvascular function, even when ejection fraction remains preserved. Extended follow-up is needed to determine the long-term clinical implications of these early findings.Myocardial and vascular biomarkersBaseline characteristics of the populations